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Alderfer's ERG (i.e., existence, relatedness, and growth) theory of motivation (1969) was adopted in this study to analyze individuals' motivations for engaging in esports. This study investigated the relatively new field of esports viewership and participation by concentrating on the motivating factors behind esports consumption to establish whether esports viewership and participation are distinct markets that stand alone or are comparable to or complement each other for consumption. The study was conducted using qualitative methods consisting of semistructured focus-group interviews. The transcript was coded using open, axial, and selective coding to develop themes fitting within the ERG theory. The current study found similarities and unique findings in esports participation and consumption motivation factors under the ERG groups. Practical applications are proposed for employing the results of the study to further marketing and development efforts in this field. [ABSTRACT FROM AUTHOR]

Aim Methods Results Conclusion As non‐operative management of rectal cancer proliferates, re‐staging and surveillance methods are critical in selecting appropriate patients for organ preservation versus proctectomy. In previous work, the authors have shown that transrectal acoustic resolution photoacoustic microscopy (ARPAM) co‐registered with ultrasound can differentiate residual cancer from complete tumoural response to neoadjuvant therapy. We hypothesize that these findings are due to changes in microvascular density (MVD).Patients with rectal adenocarcinoma who underwent neoadjuvant therapy, transrectal photoacoustic imaging and resection were included. We first compared immunohistochemical staining with erythroblast transformation‐specific‐related gene (ERG) immunostain to standard CD31 to confirm adequate identification of endothelium. Tissue sections from identical blocks were stained with CD31 and ERG, and then a correlation was calculated between manually labelled CD31‐stained vessels and ERG nuclei density. Second, representative tissue blocks from responders, partial responders and non‐responders were stained with ERG. ERG nuclei density was quantified as a proxy for MVD.CD31 MVD and ERG nuclei density were strongly correlated (R2 = 0.87; P < 0.01). In the tumour bed of patients after neoadjuvant therapy, MVD of complete responders (599 nuclei/mm2; 95% CI 434–764) is significantly higher (P < 0.01) than that of partial responders (185 nuclei/mm2; 95% CI 64–306) and non‐responders (117 nuclei/mm2; 95% CI 42–192). No significant difference was found between the partial responders and non‐responders (P = 0.60).Microvascular density appears highest in cases of complete tumour response to neoadjuvant therapy, similar to normal rectal tissue. The histological microvascular patterns seen in treated tissue may explain the imaging patterns seen in photoacoustic microscopy. [ABSTRACT FROM AUTHOR]

Purpose: Vitamin A is a lipid-soluble compound that is critical in maintaining phototransduction. Ocular manifestations of hypovitaminosis A may present with anterior segment signs of xeropthalmia, with advanced cases also causing classic retinal and electrophysiologic changes of vitamin A deficiency retinopathy. We present a case of vitamin A deficiency retinopathy, with corresponding retinal imaging and electrophysiology, in an adult patient with celiac disease and liver fibrosis. Methods: A single case report was conducted in Toronto, Canada. Results: A 77-year-old male with known celiac disease and liver fibrosis presented progressively worsening vision noticed primarily when driving. Vision was 20/50 OD and 20/200 OS. Bitot spots were noted on anterior segment examination. Fundus photography demonstrated bilateral peripheral macular hypopigmentation and far-peripheral granular retinal hypopigmentation with focal yellow dots and hyper-pigmented deposits. Optical coherence tomography (OCT) imaging demonstrated indistinct outer retinal banding with mild outer nuclear layer thinning, focal hyper-reflective deposits, and a thin choroid bilaterally. Full-field electroretinography (ERG) testing demonstrated reduced rod-isolated and combined rod-cone response amplitudes, and multifocal ERG testing demonstrated blunted individual responses throughout the field. The patient was treated with pulse vitamin A therapy. After 6 months of therapy, ERG responses were back within reference range, and the outer retinal changes reversed; visual acuity improved to 20/30 OD and 20/40 OS. Conclusion: This case represents the classic findings of vitamin A deficiency retinopathy on fundus examination and electrophysiologic testing secondary to gastrointestinal pathology. Prompt treatment of high dose vitamin A supplementation led to improvement of full-field and multifocal ERG results, as well as reconstitution of outer retinal architecture. [ABSTRACT FROM AUTHOR]

Background: It is still debatable whether the mechanisms underlying photophobia are related to altered visual cortex excitability or specific abnormalities of colour-related focal macular retino-thalamic information processing. Methods: This cross-sectional study examined Ganzfeld blue-red (B-R) and blue-yellow (B-Y) focal macular cone flash ERG (ffERG) and focal-flash visual evoked potentials (ffVEPs) simultaneously in a group of migraine patients with (n = 18) and without (n = 19) aura during the interictal phase, in comparison to a group of healthy volunteers (HVs) (n = 20). We correlate the resulting retinal and cortical electrophysiological responses with subjective discomfort from exposure to bright light verified on a numerical scale. Results: Compared to HVs, the amplitude and phase of the first and second harmonic of ffERG and ffVEPs were non-significantly different in migraine patients without aura and migraine patients with aura for both the B-R and the B-Y focal stimuli. Pearson's correlation test did not disclose correlations between clinical variables, including the photophobia scale and electrophysiological variables. Conclusions: These results do not favour interictal functional abnormalities in L-M- and S-cone opponent visual pathways in patients with migraine. They also suggest that the discomfort resulting from exposure to bright light is not related to focal macular retinal-to-visual cortex pathway. [ABSTRACT FROM AUTHOR]

The firm-sponsored online brand communities thrive on value-adding interactions. Existing studies, however, ignore the reasons for social interaction. A sufficient understanding of the factors driving social interactions and ultimately affecting community outcomes is still lacking. Our research examines how social interactions occur and influence consumer purchase behavior from a social network perspective, drawing on the theories of planned behavior and homophily. Our exponential random graph (ERG) models show that consumer-specific traits (e.g., deal proneness) and similarity on tenure, location, and deal proneness positively drive social interactions, while similarity on age, premium-product propensity does not. Our two-stage least square (2SLS) regressions find that social interactions among co-located consumers strongly influence purchase behavior. Our study contributes to the social interaction literature by emphasizing the types of social interactions and their antecedents and consequences with various consumer purposes. Our findings open a new research direction and novel business applications in firm-sponsored community management. [ABSTRACT FROM AUTHOR]

Vascular hamartoma is an abnormal development of endothelial tissue that rarely affects horses. Histopathological examination remains the gold standard for definitive diagnosis, yet the presence of abnormal vascular structures must be carefully differentiated from other vascular anomalies and neoplasms. This report describes two cases of vascular proliferation affecting the skin on the lateral side over the left tarsus and the dorsolateral region over the fetlock joint of two fillies. The clinical history, presentation, and radiographic and sonographic findings in both patients suggested a neoplasm of unknown origin. Surgical excision of the mass was successfully performed in both patients. In one patient, a second surgery was performed six months after the first surgery because of the recurrence of the mass. Histopathological examination revealed a disorganized proliferation of well-differentiated, tortuous, and varied-sized blood vessels hemmed in myxoid tissue with abundant fibrocollagenous bands. Immunohistochemical examination of the endothelium markers factor VIII and ERG revealed positive staining of the mass samples in both cases, confirming their vascular origin. The combination of these markers was effective, providing a reliable option for differentiating vascular proliferation in horses. To the best of the author’s knowledge, this is the first report applying the ERG endothelial marker to horse vascular malformations. [ABSTRACT FROM AUTHOR]

Abstract In electroretinographic (ERG) recordings of zebrafish, the light stimulus is usually delivered by a fiber optic cable. The purpose of this study was to determine whether the angle of incidence of the stimulus light from the fiber optic cable will affect the amplitudes and implicit times of the ERGs of zebrafish larvae. The larvae were positioned on their side with the right eye pointed upward. The light stimuli were delivered by a fiber optic cable from three directions of the larvae: frontal 0° (F0°), dorsal 30°(D30°), and ventral 30°(V30°). Photopic ERGs were recorded from 16 larvae at age 5–6 days post-fertilization. Our results showed that the mean amplitude of the b-wave elicited at D30° and V30° stimulation was significantly smaller than that elicited at F0° stimulation (P = 0.014 and P = 0.019, respectively). In addition, the mean amplitude of the d-wave elicited at D30° and V30° stimulation was significantly smaller than that elicited at F0° stimulation (P

Late endosomal/lysosomal adaptor, MAPK and mTOR, or LAMTOR, is a scaffold protein complex that senses nutrients and integrates growth factor signaling. The role of LAMTOR4 in tumorigenesis is still unknown. However, there is a considerable possibility that LAMTOR4 is directly involved in tumor cell proliferation and metastasis. In the current study, we investigated the protein expression of LAMTOR4 in a cohort of 314 men who were undergoing transurethral resection of prostate (TURP) consisting of incidental, advanced and castration-resistant cases. We also correlated the data with ERG and PTEN genomic status and clinicopathological features including Gleason score and patients' outcome. Additionally, we performed in vitro experiments utilizing knockdown of LAMTOR4 in prostate cell lines, and we performed mRNA expression assessment using TCGA prostate adenocarcinoma (TCGA-PRAD) to explore the potential differentially expressed genes and pathways associated with LAMTOR4 overexpression in PCa patients. Our data indicate that high LAMTOR4 protein expression was significantly associated with poor overall survival (OS) (HR: 1.44, CI: 1.01–2.05, p = 0.047) and unfavorable cause-specific survival (CSS) (HR: 1.71, CI: 1.06–2.77, p = 0.028). Additionally, when high LAMTOR4 expression was combined with PTEN-negative cases (score 0), we found significantly poorer OS (HR: 2.22, CI: 1.37–3.59, p = 0.001) and CSS (HR: 3.46, CI: 1.86–6.46, p < 0.0001). Furthermore, ERG-positive cases with high LAMTOR4 exhibited lower OS (HR: 1.98, CI: 1.18–3.31, p = 0.01) and CSS (HR: 2.54, CI: 1.32–4.87, p = 0.005). In vitro assessment showed that knockdown of LAMTOR4 decreases PCa cell proliferation, migration, and invasion. Our data further showed that knockdown of LAMTOR4 in the LNCaP cell line significantly dysregulated the β catenin/mTOR pathway and tumorigenesis associated pathways. Inhibiting components of the mTOR pathway, including LAMTOR4, might offer a strategy to inhibit tumor progression and metastasis in prostate cancer. [ABSTRACT FROM AUTHOR]

Purpose: The electroretinogram (ERG) is the summed response from all levels of the retinal processing of light, and exhibits several profound nonlinearities in the underlying processing pathways. Accurate computational models of the ERG are important, both for understanding the multifold processes of light transduction to ecologically useful signals by the retina, and for their diagnostic capabilities for the identification and characterization of retinal disease mechanisms. There are, however, very few computational models of the ERG waveform, and none that account for the full extent of its features over time. Methods: This study takes the neuroanalytic approach to modeling the ERG waveform, defined as a computational model based on the main features of the transmitter kinetics of the retinal neurons. Results: The present neuroanalytic model of the human rod ERG is elaborated from the same general principles as that of Hood and Birch (Vis Neurosci 8(2):107–126, 1992), but incorporates the more recent understanding of the early nonlinear stages of ERG generation by Robson and Frishman (Prog Retinal Eye Res 39:1–22, 2014). As a result, it provides a substantially better match than previous models of rod responses in six different waveform features of the ERG flash intensity series on which the Hood and Birch model was based. Conclusion: The neuroanalytic approach extends previous models of the component waves of the ERG, and can be structured to provide an accurate characterization of the full timecourse of the ERG waveform. The approach thus holds promise for advancing the theoretical understanding of the retinal kinetics of the light response. [ABSTRACT FROM AUTHOR]

Introduction: Mechanical sensitive channels expressed in mammalian retinas are effectors of elevated pressure stresses, but it is unclear how their activation affects visual function in pressure-related retinal disorders. Methods: This study investigated the role of the transient potential channel vanilloid TRPV4 in photoreceptors and rod bipolar cells (RBCs) with immunohistochemistry, confocal microscopy, electroretinography (ERG), and patch-clamp techniques. Results: TRPV4 immunoreactivity (IR) was found in the outer segments of photoreceptors, dendrites and somas of PKCa-positive RBCs and other BCs, plexiform layers, and retinal ganglion cells (RGCs) in wild-type mice. TRPV4-IR was largely diminished in the retinas of homozygous TRPV4 transgenic mice. Genetically suppressing TRPV4 expression moderately but significantly enhanced the amplitude of ERG a- and b-waves evoked by scotopic and mesopic lights (0.55 to 200 Rh*rod-1 s-1) and photopic lights (105-106 Rh*rod-1 s-1) compared to wildtype mice in fully dark-adapted conditions. The implicit time evoked by dim lights (0.55 to 200 Rh*rod-1 s-1) was significantly decreased for b-waves and elongated for a-waves in the transgenic mice. ERG b-wave evoked by dim lights is primarily mediated by RBCs, and under voltage-clamp conditions, the latency of the lightevoked cation current in RBCs of the transgenic mice was significantly shorter compared to wild-type mice. About 10% of the transgenic mice had one eye undeveloped, and the percentage was significantly higher than in wild-type mice. Conclusions: The data indicates that TRPV4 involves ocular development and is expressed and active in outer retinal neurons, and interventions of TRPV4 can variably affect visual signals in rods, cones, RBCs, and cone ON BCs. [ABSTRACT FROM AUTHOR]

We present a case involving a patient whose clinical phenotype aligns with oculocutaneous albinism (OCA), yet exhibits a complex genotype primarily characterized by variants of unknown significance (VUS). An 11-year-old boy manifested iris hypopigmentation and translucency, pronounced photophobia, diminished visual acuity and stereopsis, nystagmus, reduced pigmentation of the retina, and foveal hypoplasia. Genetic testing was performed. A heterozygous missense VUS CAPN5 c.230A>G, p.(Gln77Arg), a heterozygous missense VUS TYR c.1307G>C, p.(Gly436Ala), and a heterozygous missense variant TYR c.1205G>A, p.(Arg402Gln) which was classified as a risk factor, were identified. We hypothesized that the TYR c.1307G>C, p.(Gly436Ala) variant is in genetic disequilibrium with the TYR c.1205G>A, p.(Arg402Gln) variant leading to deficient expression of melanogenic enzymes in retinal cells, resulting in the manifestation of mild OCA. Additionally, this study represents the case where we did not detect chiasmal misrouting in visual evoked potentials, nor did we observe a shift in the distribution of ganglion cell thickness from a temporal to a central position. Moreover, our patient's case supports the probable benign nature of the CAPN5 c.230A>G, p.(Gln77Arg) variant. [ABSTRACT FROM AUTHOR]

Arsenite-resistance protein 2, also known as serrate RNA effector molecule (ARS2/SRRT), is known to be involved in cellular proliferation and tumorigenicity. However, its role in prostate cancer (PCa) has not yet been established. We investigated the potential role of SRRT in 496 prostate samples including benign, incidental, advanced, and castrate-resistant patients treated by androgen deprivation therapy (ADT). We also explored the association of SRRT with common genetic aberrations in lethal PCa using immunohistochemistry (IHC) and performed a detailed analysis of SRRT expression using The Cancer Genome Atlas (TCGA PRAD) by utilizing RNA-seq, clinical information (pathological T category and pathological Gleason score). Our findings indicated that high SRRT expression was significantly associated with poor overall survival (OS) and cause-specific survival (CSS). SRRT expression was also significantly associated with common genomic aberrations in lethal PCa such as PTEN loss, ERG gain, mutant TP53, or ATM. Furthermore, TCGA PRAD data revealed that high SRRT mRNA expression was significantly associated with higher Gleason scores, PSA levels, and T pathological categories. Gene set enrichment analysis (GSEA) of RNAseq data from the TCGA PRAD cohort indicated that SRRT may play a potential role in regulating the expression of genes involved in prostate cancer aggressiveness. Conclusion: The current data identify the SRRTs potential role as a prognostic for lethal PCa, and further research is required to investigate its potential as a therapeutic target.

Background Atypical small acinar proliferation (ASAP) cases typically require rebiopsy, which are invasive and associated with increased risk of complications. Our aim in this study was to determine the importance of laboratory and histological findings and E-26 transformation-specific-related gene (ERG) expression in the diagnosis of malignancy. Methods Between March 2016 and March 2022, 84 patients who were diagnosed with ASAP on biopsy or rebiopsy were included in the study. Clinical-laboratory features of age, serum prostate-specific antigen level, and histopathological features were compared and included multifocality, number of suspicious acini, nuclear enlargement, nucleolar prominence, hyperchromasia, cytoplasmic amphophilia, luminal amorphous acellular secretion, crystalloid presence, infiltrative appearance, inflammation, atrophy, α-methyl acyl-CoA racemase, p63, and/or high molecular weight cytokeratin were analyzed. In addition, ERG expression was evaluated immunohistochemically. Results Statistically significant correlation was found between nucleolar prominence, nuclear hyperchromasia, crystalloid presence, infiltrative pattern, and prostate cancer (p < .001). In 19 of 84 cases (22.6%) ERG was positive in the nucleus. Prostate cancer was diagnosed at rebiopsy in 15 of the 19 ERG-positive cases (78.9%). A statistically significant correlation was found between ERG positivity and prostate cancer (p= .002). Conclusions Our findings suggest that evaluation of these markers during initial transrectal ultrasound biopsies may decrease and prevent unnecessary prostate rebiopsy.

Abstract Background Prostate cancer is the leading cause of cancer-related death and the second most commonly diagnosed cancer among men in Uganda and most countries in Sub-Saharan Africa (SSA). The TMPRSS2-ERG fusion gene is the most common genetic alteration seen among prostate cancer patients. There are several contradicting reports about the association of ERG protein with poor prognosis, high PSA, and Gleason score. This study determined the prevalence of ERG expression and the relationship with PSA, Gleason score, and Age of prostate cancer patients in Southwestern Uganda. Methods We reviewed 130 archived prostate biopsy (needle and TURP) specimens from patients of age ≥ 50 years who had a histological diagnosis of prostate cancer. We obtained their biodata, and preoperative PSA, from the archived records. We did Immunohistochemistry (IHC) to determine the prevalence of ERG expression. Results The mean patient age in our study was 74.64 ± 10.19 years. Pre-operative PSA levels had been done for 79.2% of the participants. Most cancers (58.46%) were of high grade (grade group 3–5). ERG expression prevalence was 75.4% and its expression was independent of age, re-operative PSA, and Gleason score. Conclusion There is a significantly higher prevalence of ERG expression in our study compared to what is reported in other African-based studies. The expression of the ERG is independent of age, Gleason score, and serum PSA levels. A high proportion of our prostate cancer has high-grade disease at the time of diagnosis.

The global rate of Amphotericin B (AmB) resistance in Candida auris has surpassed 12%. However, there is limited data on available clinical treatments and microevolutionary analyses concerning reduced AmB sensitivity. In this study, we collected 18 C. auris isolates from five patients between 2019 and 2022. We employed clinical data mining, genomic, and transcriptomic analyses to identify genetic evolutionary features linked to reduced AmB sensitivity in these isolates during clinical treatment. We identified six isolates with a minimum inhibitory concentration (MIC) of AmB below 0.5 µg/mL (AmB0.5) and 12 isolates with an AmB-MIC of 1 µg/mL (AmB1) or ≥ 2 µg/mL (AmB2). All five patients received 24-hour AmB (5 mg/L) bladder irrigation treatment. Evolutionary analyses revealed an ERG3 (c923t) mutation in AmB1 C. auris. Additionally, AmB2 C. auris was found to contain a t2831c mutation in the RAD2 gene. In the AmB1 group, membrane lipid-related gene expression (ERG1, ERG2, ERG13, and ERG24) was upregulated, while in the AmB2 group, expression of DNA-related genes (e.g. DNA2 and PRI1) was up-regulated. In a series of C.auris strains with reduced susceptibility to AmB, five key genes were identified: two upregulated (IFF9 and PGA6) and three downregulated (HGT7, HGT13,and PRI32). In this study, we demonstrate the microevolution of reduced AmB sensitivity in vivo and further elucidate the relationship between reduced AmB sensitivity and low-concentration AmB bladder irrigation. These findings offer new insights into potential antifungal drug targets and clinical markers for the “super fungus”, C. auris.

Background: Prostate cancer is the leading cause of cancer-related death and the second most commonly diagnosed cancer among men in Uganda and most countries in Sub-Saharan Africa (SSA). The TMPRSS2-ERG fusion gene is the most common genetic alteration seen among prostate cancer patients. There are several contradicting reports about the association of ERG protein with poor prognosis, high PSA, and Gleason score. This study determined the prevalence of ERG expression and the relationship with PSA, Gleason score, and Age of prostate cancer patients in Southwestern Uganda. Methods: We reviewed 130 archived prostate biopsy (needle and TURP) specimens from patients of age ≥ 50 years who had a histological diagnosis of prostate cancer. We obtained their biodata, and preoperative PSA, from the archived records. We did Immunohistochemistry (IHC) to determine the prevalence of ERG expression. Results: The mean patient age in our study was 74.64 ± 10.19 years. Pre-operative PSA levels had been done for 79.2% of the participants. Most cancers (58.46%) were of high grade (grade group 3–5). ERG expression prevalence was 75.4% and its expression was independent of age, re-operative PSA, and Gleason score. Conclusion: There is a significantly higher prevalence of ERG expression in our study compared to what is reported in other African-based studies. The expression of the ERG is independent of age, Gleason score, and serum PSA levels. A high proportion of our prostate cancer has high-grade disease at the time of diagnosis. [ABSTRACT FROM AUTHOR]

A challenging task in routine practice is finding the distinction between benign and malignant paragangliomas and pheochromocytomas. The aim of this study is to conduct a comparative analysis of angiogenesis by assessing intratumoral microvascular density (MVD) with immunohistochemical (IHC) markers (CD31, CD34, CD105, ERG), and S100 immunoreactivity, Ki67 proliferative index, succinate dehydrogenase B (SDHB) expressiveness, tumor size with one the most utilized score Pheochromocytoma of Adrenal Gland Scales Score (PASS), using tissue microarray (TMA) with 115 tumor samples, 61 benign (PASS < 4) and 54 potentially malignant (PASS ≥ 4). We found no notable difference between intratumoral MVD and potentially malignant behavior. The group of potentially malignant tumors is significantly larger in size, has lower intratumoral MVD, and a decreased number of S100 labeled sustentacular cells. Both groups have low proliferative activity (mean Ki67 is 1.02 and 1.22, respectively). Most tumors maintain SDHB expression, only 6 cases (5.2%) showed a loss of expression (4 of them in PASS < 4 group and 2 in PASS ≥ 4). PASS score is easily available for assessment and complemented with markers of biological behavior to complete the risk stratification algorithm. Size is directly related to PASS score and malignancy. Intratumoral MVD is extensively developed but it is not crucial in evaluating the malignant potential. [ABSTRACT FROM AUTHOR]

Background & Objective: Prostatic adenocarcinoma (PAC) is the second most prevalent cancer and the fifth leading cause of cancer death in men worldwide. Additionally, pathologists may face problems diagnosing it reliably and may need more than one marker. Thus, the search for new immunohistochemical biomarkers becomes mandatory. This study aims to investigate P4HB and SOX4 expression in prostatic carcinoma, their possible roles, and clinical significance. Methods: This retrospective study included fifty-six cases of PAC and an equal number of nodular prostatic hyperplasia (NPH) that were immunohistochemically stained by P4HB and SOX4. The results of expression were compared between PAC and NPH cases, followed by correlations with available clinicopathological parameters. Results: There was a highly significant difference between PAC and NPH regarding P4HB and SOX4 expressions in favor of PAC (both P<0.001). ROC curve analysis of the diagnostic power of P4HB showed 79% sensitivity, 76% specificity, and an area under the ROC curve of 0.845, while SOX4 showed (89%, 100%, and 0.946, respectively). P4HB and SOX4 expression showed a direct correlation (P<0.001). Moreover, the H-score of SOX4 expression showed a significant inverse relation with ERG expression (P=0.047). There was a significant correlation between P4HB and SOX4 and Gleason score (P<0.001). Moreover, P4HB expression was significantly associated with lymphovascular invasion (P=0.013), while SOX4 expression showed a significant association with perineural invasion (P=0.05). Conclusion: SOX4 and P4HB seem to have diagnostic and prognostic value in PAC. While there was a direct correlation between SOX4 and P4HB, an inverse relationship between SOX4 and ERG was detected. [ABSTRACT FROM AUTHOR]

The study of dunes morphology provides a valuable tool in the investigation of wind systems and as result the identification of sand sources (removal region). The wind direction is the primary factor controlling the dune shape and elongation. In deserts exposed to wind from different directions and with comparable magnitude, dunes are formed to be different morphology. The sand dunes are either fapendicular or parallel to the wind direction.The purpose of this pafa is to analyze the morphology of sand dunes under bimodal winds using conventional models. Observations showed that the linear (seif dune) dunes formation are due to the elongation of a barchan horn. So that, these dunes create by a bimodal wind regime with a strong peak from the result of northwest and west winds and a weaker peak from the east winds with a divergence angle of 135°. Sinuous crest lines of seif dune grow directly by west and east winds. Studies have also shown that the evolution trend of the sand dunes of the region, under the strong northwest wind, first shield dune transforms into a dihedral barchans. At this stage, Wind erosion on the back of the sand pile (shield dune) leads to the formation of a crest fapendicular to the wind direction and so to the formation of a slip face downwind. According to the effect of the magnitude and change of direction in the Westerly and Easterly winds, the western wing of barchan begins to extend and turns into a dentate seif dune. [ABSTRACT FROM AUTHOR]

Simple Summary: SETD2, a histone methyltransferase and epigenetic modifier, and SETD2 protein expression were explored in a prostate cancer non-surgical cohort of 202 cases. Notably, SETD2 showed higher intensity in advanced and castrate-resistant disease compared to incidental cases. Moreover, elevated SETD2 expression is significantly associated with poorer prognosis, lower overall survival (OS), and decreased cancer-specific survival (CSS). High-risk SETD2 combined with PTEN loss or ERG positivity improved the prognostication for these outcomes. Additionally, the TCPA protein database and TCGA PRAD GSEA implicated SETD2 in pathways linked to tumor progression, chemoresistance, and adverse prognosis, including the AMPK, cAMP, and PI3K-Akt signaling pathways. SET-domain containing 2 (SETD2) is a histone methyltransferase and an epigenetic modifier with oncogenic functionality. In the current study, we investigated the potential prognostic role of SETD2 in prostate cancer. A cohort of 202 patients' samples was assembled on tissue microarrays (TMAs) containing incidental, advanced, and castrate-resistant CRPCa cases. Our data showed significant elevated SETD2 expression in advanced and castrate-resistant disease (CRPCa) compared to incidental cases (2.53 ± 0.58 and 2.21 ± 0.63 vs. 1.9 ± 0.68; p < 0.001, respectively). Interestingly, the mean intensity of SETD2 expression in deceased vs. alive patients was also significantly different (2.31 ± 0.66 vs. 2 ± 0.68; p = 0.003, respectively). Overall, high SETD2 expression was found to be considered high risk and was significantly associated with poor prognosis and worse overall survival (OS) (HR 1.80; 95% CI: 1.28–2.53, p = 0.001) and lower cause specific survival (CSS) (HR 3.14; 95% CI: 1.94–5.08, p < 0.0001). Moreover, combining high-intensity SETD2 with PTEN loss resulted in lower OS (HR 2.12; 95% CI: 1.22–3.69, p = 0.008) and unfavorable CSS (HR 3.74; 95% CI: 1.67–8.34, p = 0.001). Additionally, high SETD2 intensity with ERG positive expression showed worse prognosis for both OS (HR 1.99, 95% CI 0.87–4.59; p = 0.015) and CSS (HR 2.14, 95% CI 0.98–4.68, p = 0.058). We also investigated the protein expression database TCPA, and our results showed that high SETD2 expression is associated with a poor prognosis. Finally, we performed TCGA PRAD gene set enrichment analysis (GSEA) data for SETD2 overexpression, and our data revealed a potential association with pathways involved in tumor progression such as the AMPK signaling pathway, the cAMP signaling pathway, and the PI3K-Akt signaling pathway, which are potentially associated with tumor progression, chemoresistance, and a poor prognosis. [ABSTRACT FROM AUTHOR]

Introduction/background: Phosphatase and tensin homolog (PTEN) genomic deletions and transmembrane protease, serine 2/v-ets avian erthyroblastosis virus E26 oncogene homolog (ERG) rearrangements are two of the most common genetic abnormalities associated with prostate cancer. Prior studies have demonstrated these alterations portend worse clinical outcomes. Our objective is to evaluate the impact of biopsy-determined PTEN losses and TMPRSS2-ERG fusion on biochemical progression-free survival (bPFS) and overall survival (OS) in patients who receive SBRT for localized prostate cancer. Methods/materials: Patients received SBRT for localized prostate cancer on a prospective quality-of-life (QoL) and cancer outcomes study. For each patient, the single biopsy core with the highest grade/volume of cancer was evaluated for PTEN and ERG abnormalities. Differences in baseline patient and disease characteristics between groups were analyzed using ANOVA for age and X² for categorical groupings. bPFS and OS were calculated using the Kaplan Meier (KM) method with Log-Rank test comparison between groups. Predictors of bPFS and OS were identified using the Cox proportional hazards method. For all analyses, p <0.05 was considered statistically significant. Results: Ninety-nine consecutive patients were included in the analysis with a median follow-up of 72 months. A statistically significant improvement in bPFS (p = 0.018) was observed for wild type ERG patients with an estimated 5-year bPFS of 94.1% vs. 72.4%. Regarding PTEN mutational status, significant improvements in were observed in both bPFS (p = 0.006) and OS (p < 0.001), with estimated 5-year bPFS rates of 91.0% vs. 67.9% and 5-year OS rates of 96.4% vs. 79.4%. When including both ERG and PTEN mutational status in the analysis, there were statistically significant differences in both bPFS (p = 0.011) and OS (p < 0.001). The estimated 5-year bPFS rates were 100%, 76.6%, 72.9%, and 63.8% for patients with ERG+/PTEN+, ERG-/PTEN+, ERG+/PTEN-, and ERG-/PTEN- phenotypes respectively. The estimated 5-year OS rates were 93.9%, 100%, 80.0%, and 78.7% for patients with ERG+/PTEN+, ERG-/PTEN+, ERG+/PTEN-, and ERG-/PTENphenotypes respectively. Conclusion: ERG rearrangements and PTEN deletions detected on biopsy samples are associated with poorer oncologic outcomes in prostate cancer patients treated with SBRT and merit further study in a dedicated prospective trial. [ABSTRACT FROM AUTHOR]

The brown marmorated stink bug (Halyomorpha halys) is an invasive pest insect species, which was recently introduced from Asia to America and then to Europe. Besides causing serious damage in agriculture, this species also represents a source of intense annoyance for humans in residential areas, because large amounts of individuals can aggregate on buildings while seeking shelter before overwintering. Taking into account the need for pesticide-free pest management methods, for example light trapping, we measured the spectral sensitivity of the compound eyes of H. halys with electroretinography (ERG). In behavioural experiments, we also quantified the attraction of H. halys to 14 quasi-monochromatic light stimuli in the 368–743 nm spectral range. The dark-adapted compound eyes were mostly sensitive to the green range, but a minor sensitivity peak in the UV region was also identified. Recordings on chromatic-adapted eye preparations unequivocally revealed the presence of only a green- and a UV-sensitive photoreceptor type, with sensitivity maxima at 519 nm and 367 nm, respectively. No sign of any blue-sensitive receptor was detected, and thus only a receptor set allowing dichromatic vision was found. Based on the results of the behavioural experiments, we established that the attraction of H. halys to light is increasing with decreasing wavelength, and thus we emphasize the importance of short wavelength lights (368–455 nm) when phototactic attraction of H. halys is the aim. [ABSTRACT FROM AUTHOR]

Pseudomyogenic hemangioendothelioma (PHE) is an uncommon mesenchymal neoplasm of intermediate malignant potential showing endothelial differentiation. Around 20 cases of primary osseous PHE have been reported to date. A 16-year-old boy presented with complaints of pain in his right leg. Imaging revealed multifocal intramedullary and cortical-based lytic lesions involving long and small bones. Microscopic examination revealed plump, spindled cells arranged in fascicles and admixed “epithelioid” and “rhabdoid” cells sans vasoformative areas. By immunohistochemistry, the lesional cells were reactive for AE1/AE3, CD31, Erg, Fli1, and SMA, while immunonegative for CD34, myogenin, and S100. Nuclear expression of the INI1/SMARCB1 protein was retained. PHE is a rare entity, more so as a primary osseous lesion; therefore, awareness of the presence of this entity in the bone is the key to making a diagnosis. We discuss its clinicopathological features, differential diagnosis, and an attempt a short review of the literature.

Background: Prostate cancer (PCa) is the second most common malignancy in men and the sixth leading cause of death. Clinical course of PCa is highly variable and current clinico pathological parameters are unable to predict accurately the course of the disease because of genetic heterogeneity seen in this tumor. Aims and Objectives: The aim of the study was to study the prevalence of E26 transformation-specific-related gene (ERG) expression in benign and malignant lesions of prostate in Northern Indian patients. Whether ERG expression using immunohistochemical (IHC) methods can also be used for differentiating various lesions of the prostate gland is also evaluated. Materials and Methods: This is an observational study conducted on 50 biopsy specimens encompassing different lesions of prostate. The study was carried out in the Department of Pathology at Integral Institute of Medical Sciences and Research, Lucknow, India, during the period January 2020–September 2022. Results: Amongst 50 cases of prostatic lesions included in the study, there were 20 cases of benign prostatic hyperplasia (BPH), 17 cases of benign mimicker lesions and 13 cases of PCa. ERG expression was absent in all cases of BPH and benign mimicker lesions. ERG expression was seen in 38.5% of cases of PCa. Conclusion: In our study, none of the patients of BPH or benign mimicker lesion expressed ERG on IHC, while 38.5% of patients of PCa showed positive staining. This figure differs from reports from other parts of the world. ERG expressions can be a potential therapeutic target for personalized treatment in a subset of patients of PCa. However, it was not found to be a sensitive marker for the diagnosis of PCa.

The electroretinogram (ERG) is a clinical test that records the retina’s electrical response to a brief flash of light as a waveform signal. Analysis of the ERG signal offers a promising non-invasive method for studying different neurodevelopmental and neurodegenerative disorders. Autism Spectrum Disorder (ASD) is a neurodevelopmental condition characterized by poor communication, reduced reciprocal social interaction, and restricted and repetitive stereotyped behaviors that should be detected as early as possible to ensure timely and appropriate intervention to support the individual and their family. In this study, we applied gated Multilayer Perceptron (gMLP) for the light-adapted ERG waveform classification as an effective alternative to Transformers. This study presents the first application of gMLP for ASD classification, which employs basic multilayer perceptrons with fewer parameters than Transformers. We compared the performance of different time-series models on an ASD-Control dataset and found that the superiority of gMLP in classification accuracy was the best at 89.7% compared to alternative models and supports the use of gMLP in classification models based on ERG recordings involving case-control comparisons.

Abstract Introduction Lung adenocarcinoma (LUAD) is the major type of non‐small cell lung cancer with low a survival rate caused by metastasis. SCN4B encoding voltage‐gated sodium channel β subunit is regarded as a metastasis‐suppressor gene. We aim to explore how SCN4B influences the progression and prognosis of LUAD. Methods The gene expression profiles of 585 LUAD samples in TCGA and GSE31210, GSE116959, and GSE72094 datasets from the GEO database were downloaded for analysis. Differentially expressed genes were obtained through the “limma” package. The “clusterProfiler” package was used to conduct GSEA. Survival analysis was conducted via “survival” and “survminer” packages. Transcription factors regulating SCN4B expression were screened by correlation analysis and further predicted by FIMO. Infiltration of immune cells was analyzed by CIBERSORT. ESTIMATE algorithm was used to evaluate the immune‐related scores. Results SCN4B expressed higher in normal samples than in LUAD samples and higher in female samples than male samples. One hundred and twenty‐six pathways were significantly enriched between high and low SCN4B expression groups. Six transcription factors' expressions were positively related to SCN4B expression, and ChIP‐seq data from “Cistrome” verified that TAL1 and ERG might bind to the upstream sequence of SCN4B. SCN4B expression was significantly correlated with activated memory CD4 T cells, resting mast cells, and monocytes. TMB status, three scores based on ESTIMATE algorithm, and expression of three immune checkpoints showed significant differences between SCN4B high‐ and low‐expression groups. SCN4B could be considered as an independent prognostic signature of LUAD patients that higher expression represents a better prognosis. Conclusion SCN4B expresses higher in normal samples, and SCN4B is able to be an independent prognostic signature for LUAD patients. TAL1 and ERG may regulate the expression of SCN4B by binding its upstream sequences. Our research is valuable in improving the effectiveness of treatment in LUAD.

Pathogenic variants in BEST1 can cause autosomal dominant or autosomal recessive dystrophy, typically associated with distinct retinal phenotypes. In heterozygous cases, the disorder is commonly characterized by yellow sub-macular lesions in the early stages, known as Best vitelliform macular dystrophy (BVMD). Biallelic variants usually cause a more severe phenotype including diffuse retinal pigment epithelial irregularity and widespread generalized progressive retinopathy, known as autosomal recessive bestrophinopathy (ARB). This study describes three cases with clinical changes consistent with BVMD, however, unusually associated with autosomal recessive inheritance. Detailed ophthalmic workup included comprehensive ophthalmologic examination, multimodal retinal imaging, full-field and pattern electroretinography (ERG; PERG), and electrooculogram (EOG). Genetic analysis of probands and segregation testing and fundus examination of proband relatives was performed where possible. Three unrelated cases presented with a clinical phenotype typical for BVMD and were found to have biallelic disease-causing variants in BEST1. PERG P50 and ERG were normal in all cases. The EOG was subnormal (probands 1 and 3) or normal/borderline (proband 2). Probands 1 and 2 were homozygous for the BEST1 missense variant c.139C>T, p.Arg47Cys, while proband 3 was homozygous for a deletion, c.536_538delACA, p.Asn179del. The parents of proband 1 were phenotypically normal. Parents of proband 1 and 2 were heterozygous for the same missense variant. Individuals with biallelic variants in BEST1 can present with a phenotype indistinguishable from BVMD. The same clinical phenotype may not be evident in those harboring the same variants in the heterozygous state. This has implications for genetic counselling and prognosticationA. [ABSTRACT FROM AUTHOR]

Background: Prostate cancer (PCa) is the second most common malignancy in men and the sixth leading cause of death. Clinical course of PCa is highly variable and current clinico pathological parameters are unable to predict accurately the course of the disease because of genetic heterogeneity seen in this tumor. Aims and Objectives: The aim of the study was to study the prevalence of E26 transformation-specific-related gene (ERG) expression in benign and malignant lesions of prostate in Northern Indian patients. Whether ERG expression using immunohistochemical (IHC) methods can also be used for differentiating various lesions of the prostate gland is also evaluated. Materials and Methods: This is an observational study conducted on 50 biopsy specimens encompassing different lesions of prostate. The study was carried out in the Department of Pathology at Integral Institute of Medical Sciences and Research, Lucknow, India, during the period January 2020-September 2022. Results: Amongst 50 cases of prostatic lesions included in the study, there were 20 cases of benign prostatic hyperplasia (BPH), 17 cases of benign mimicker lesions and 13 cases of PCa. ERG expression was absent in all cases of BPH and benign mimicker lesions. ERG expression was seen in 38.5% of cases of PCa. Conclusion: In our study, none of the patients of BPH or benign mimicker lesion expressed ERG on IHC, while 38.5% of patients of PCa showed positive staining. This figure differs from reports from other parts of the world. ERG expressions can be a potential therapeutic target for personalized treatment in a subset of patients of PCa. However, it was not found to be a sensitive marker for the diagnosis of PCa. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the role of ERG in the HLX/STAT4/Perforin signaling axis, impacting natural killer (NK) cell cytotoxicity and myocardial infarction (MI) progression. NK cell cytotoxicity was assessed via co-culture and 51Cr release assays. Datasets GSE34198 and GSE97320 identified common differentially expressed genes in MI. NK cell gene expression was analyzed in MI patients and healthy individuals using qRT-PCR and Western blotting. ERG's regulation of HLX and STAT4's regulation of perforin were studied through computational tools (MEM) and ChIP experiments. HLX's influence on STAT4 was explored with the MG132 proteasome inhibitor. Findings were validated in a mouse MI model. ERG, a commonly upregulated gene, was identified in NK cells from MI patients and mice. ERG upregulated HLX, leading to STAT4 proteasomal degradation and reduced Perforin expression. Consequently, NK cell cytotoxicity decreased, promoting MI progression. ERG mediates the HLX/STAT4/Perforin axis to inhibit NK cell cytotoxicity, fostering MI progression. These results provide vital insights into MI's molecular mechanisms. [ABSTRACT FROM AUTHOR]

Targeted electric signal use for disease diagnostics and treatment is emerging as a healthcare game-changer. Besides arrhythmias, treatment-resistant epilepsy and chronic pain, blindness, and perhaps soon vision loss, could be among the pathologies that benefit from bioelectronic medicine. The electroretinogram (ERG) technique has long demonstrated its role in diagnosing eye diseases and early stages of neurodegenerative diseases. Conspicuously, ERG applications are all based on light-induced responses. However, spontaneous, intrinsic activity also originates in retinal cells. It is a hallmark of degenerated retinas and its alterations accompany obesity and diabetes. To the extent that variables extracted from the resting activity of the retina measured by ERG allow the predictive diagnosis of risk factors for type 2 diabetes. Here, we provided a comparison of the baseline characteristics of intrinsic oscillatory activity recorded by ERGs in mice, rats, and humans, as well as in several rat strains, and explore whether zebrafish exhibit comparable activity. Their pattern was altered in neurodegenerative models including the cuprizone-induced demyelination model in mice as well as in the Royal College of Surgeons (RCS-/-) rats. We also discuss how the study of their properties may pave the way for future research directions and treatment approaches for retinopathies, among others. [ABSTRACT FROM AUTHOR]

Background and Objectives: Prognostic biomarkers in prostate cancer (PCa) include PTEN, ERG, SPINK1, and TFF3. Their relationships and patterns of expression in PCa in developing countries, including Jordan, have not yet been investigated. Materials and Methods: A tissue microarray (TMA) of PCa patients was taken from paraffin-embedded tissue blocks for 130 patients. PTEN, ERG, SPINK1, and TFF3 expression profiles were examined using immunohistochemistry (IHC) and correlated with each other and other clinicopathological factors. Results: PTEN loss of any degree was observed in 42.9% of PCa cases. ERG and TFF3 were expressed in 59.3% and 46.5% of PCa cases, respectively. SPINK1 expression was observed in 6 out of 104 PCa cases (5.4%). Among all PCa cases (n = 104), 3.8% (n = 4) showed SPINK1+/ERG+ phenotype, 1.9% (n = 2) showed SPINK1+/ERG- phenotype, 56.7% (n = 59) showed SPINK1-/ERG+ phenotype, and 37.5% showed SPINK1-/ERG- phenotype (n = 39). Among ERG positive cases (n = 63), 6.3% were SPINK1 positive. Among SPINK1 positive cases (n = 6), 66.7% were ERG positive. SPINK1 expression was predominantly observed in a subgroup of cancers that expressed TFF3 (6/6). Additionally, a statistically significant loss of PTEN expression was observed from Gleason Score 6 (GS6) (Grade Group 1 (GG1)) to GS9-10 (GG5); (p-value 0.019). Conclusions: This is the first study to look at the status of the PTEN, ERG, SPINK1, and TFF3 genes in a Jordanian Arab population. Loss of PTEN has been linked to more aggressive prostate cancer with high GSs/GGs. SPINK1 expression was predominantly observed in a subgroup of cancers that expressed TFF3. Our results call for screening these biomarkers for grading and molecular subtyping of the disease. [ABSTRACT FROM AUTHOR]

Retinitis pigmentosa is an inherited disease, in which mutations in different types of genes lead to the death of photoreceptors and the loss of visual function. Although retinitis pigmentosa is the most common type of inherited retinal dystrophy, a clear line of therapy has not yet been defined. In this review, we will focus on the therapeutic aspect and attempt to define the advantages and disadvantages of the protocols of different therapies. The role of some therapies, such as antioxidant agents or gene therapy, has been established for years now. Many clinical trials on different genes and mutations causing RP have been conducted, and the approval of voretigene nepavorec by the FDA has been an important step forward. Nonetheless, even if gene therapy is the most promising type of treatment for these patients, other innovative strategies, such as stem cell transplantation or hyperbaric oxygen therapy, have been shown to be safe and improve visual quality during clinical trials. The treatment of this disease remains a challenge, to which we hope to find a solution as soon as possible. [ABSTRACT FROM AUTHOR]

Introduction: Lung adenocarcinoma (LUAD) is the major type of non‐small cell lung cancer with low a survival rate caused by metastasis. SCN4B encoding voltage‐gated sodium channel β subunit is regarded as a metastasis‐suppressor gene. We aim to explore how SCN4B influences the progression and prognosis of LUAD. Methods: The gene expression profiles of 585 LUAD samples in TCGA and GSE31210, GSE116959, and GSE72094 datasets from the GEO database were downloaded for analysis. Differentially expressed genes were obtained through the "limma" package. The "clusterProfiler" package was used to conduct GSEA. Survival analysis was conducted via "survival" and "survminer" packages. Transcription factors regulating SCN4B expression were screened by correlation analysis and further predicted by FIMO. Infiltration of immune cells was analyzed by CIBERSORT. ESTIMATE algorithm was used to evaluate the immune‐related scores. Results: SCN4B expressed higher in normal samples than in LUAD samples and higher in female samples than male samples. One hundred and twenty‐six pathways were significantly enriched between high and low SCN4B expression groups. Six transcription factors' expressions were positively related to SCN4B expression, and ChIP‐seq data from "Cistrome" verified that TAL1 and ERG might bind to the upstream sequence of SCN4B. SCN4B expression was significantly correlated with activated memory CD4 T cells, resting mast cells, and monocytes. TMB status, three scores based on ESTIMATE algorithm, and expression of three immune checkpoints showed significant differences between SCN4B high‐ and low‐expression groups. SCN4B could be considered as an independent prognostic signature of LUAD patients that higher expression represents a better prognosis. Conclusion: SCN4B expresses higher in normal samples, and SCN4B is able to be an independent prognostic signature for LUAD patients. TAL1 and ERG may regulate the expression of SCN4B by binding its upstream sequences. Our research is valuable in improving the effectiveness of treatment in LUAD. [ABSTRACT FROM AUTHOR]

Aims: A cribriform pattern, reactive stroma (RS), PTEN, Ki67 and ERG are promising prognostic biomarkers in primary prostate cancer (PCa). We aim to determine the relative contribution of these factors and the Cancer of the Prostate Risk Assessment Postsurgical (CAPRA‐S) score in predicting PCa prognosis. Methods and results: We included 475 patients who underwent radical prostatectomy (2010–12, median follow‐up = 8.7 years). Cribriform pattern was identified in 57% of patients, PTEN loss in 55%, ERG expression in 51%, RS in 39% and high Ki67 in 9%. In patients with multiple samples from the same malignant focus and either PTEN loss or high Ki67, intrafocal heterogeneity for PTEN and Ki67 expression was detected in 55% and 89%, respectively. In patients with samples from two or more foci, interfocal heterogeneity was detected in 46% for PTEN and 6% for Ki67. A cribriform pattern and Ki67 were independent predictors of biochemical recurrence (BCR) and clinical recurrence (CR), whereas ERG expression was an independent predictor of CR. Besides CAPRA‐S, a cribriform pattern provided the highest relative proportion of explained variation for predicting BCR (11%), and Ki67 provided the highest relative proportion of explained variation for CR (21%). In patients with a cribriform pattern, high Ki67 was associated with a higher risk of BCR [hazard ratio (HR) = 2.83, P < 0.001] and CR (HR = 4.35, P < 0.001). Conclusions: High Ki67 in patients with a cribriform pattern identifies a patient subgroup with particularly poor prognosis, which we termed 'high proliferative cribriform prostate cancer'. These results support reporting a cribriform pattern in pathology reports, and advocate implementing Ki67. [ABSTRACT FROM AUTHOR]

Heterogeneity in endothelial cell (EC) sub-phenotypes is becoming increasingly appreciated in atherosclerosis progression. Still, studies quantifying EC heterogeneity across whole transcriptomes and epigenomes in both in vitro and in vivo models are lacking. Multiomic profiling concurrently measuring transcriptomes and accessible chromatin in the same single cells was performed on six distinct primary cultures of human aortic ECs (HAECs) exposed to activating environments characteristic of the atherosclerotic microenvironment in vitro. Meta-analysis of single-cell transcriptomes across 17 human ex vivo arterial specimens was performed and two computational approaches quantitatively evaluated the similarity in molecular profiles between heterogeneous in vitro and ex vivo cell profiles. HAEC cultures were reproducibly populated by four major clusters with distinct pathway enrichment profiles and modest heterogeneous responses: EC1-angiogenic, EC2-proliferative, EC3-activated/mesenchymal-like, and EC4-mesenchymal. Quantitative comparisons between in vitro and ex vivo transcriptomes confirmed EC1 and EC2 as most canonically EC-like, and EC4 as most mesenchymal with minimal effects elicited by siERG and IL1B. Lastly, accessible chromatin regions unique to EC2 and EC4 were most enriched for coronary artery disease (CAD)-associated single-nucleotide polymorphisms from Genome Wide Association Studies (GWAS), suggesting that these cell phenotypes harbor CAD-modulating mechanisms. Primary EC cultures contain markedly heterogeneous cell subtypes defined by their molecular profiles. Surprisingly, the perturbations used here only modestly shifted cells between subpopulations, suggesting relatively stable molecular phenotypes in culture. Identifying consistently heterogeneous EC subpopulations between in vitro and ex vivo models should pave the way for improving in vitro systems while enabling the mechanisms governing heterogeneous cell state decisions.

Endothelial cell subpopulations are characterized by unique gene expression profiles, epigenetic landscapes and functional properties.

Introduction/backgroundPhosphatase and tensin homolog (PTEN) genomic deletions and transmembrane protease, serine 2/v-ets avian erthyroblastosis virus E26 oncogene homolog (ERG) rearrangements are two of the most common genetic abnormalities associated with prostate cancer. Prior studies have demonstrated these alterations portend worse clinical outcomes. Our objective is to evaluate the impact of biopsy-determined PTEN losses and TMPRSS2-ERG fusion on biochemical progression-free survival (bPFS) and overall survival (OS) in patients who receive SBRT for localized prostate cancer.Methods/materialsPatients received SBRT for localized prostate cancer on a prospective quality-of-life (QoL) and cancer outcomes study. For each patient, the single biopsy core with the highest grade/volume of cancer was evaluated for PTEN and ERG abnormalities. Differences in baseline patient and disease characteristics between groups were analyzed using ANOVA for age and χ2 for categorical groupings. bPFS and OS were calculated using the Kaplan Meier (KM) method with Log-Rank test comparison between groups. Predictors of bPFS and OS were identified using the Cox proportional hazards method. For all analyses, p

Signal integration of converging neural circuits is poorly understood. One example is in the retina where the integration of rod and cone signaling is responsible for the large dynamic range of vision. The relative contribution of rods versus cones is dictated by a complex function involving background light intensity and stimulus temporal frequency. One understudied mechanism involved in coordinating rod and cone signaling onto the shared retinal circuit is the hyperpolarization activated current (Ih) mediated by hyperpolarization-activated cyclic nucleotide-gated 1 (HCN1) channels expressed in rods and cones. Ih opposes membrane hyperpolarization driven by activation of the phototransduction cascade and modulates the strength and kinetics of the photoreceptor voltage response. We examined conditional knock-out (KO) of HCN1 from mouse rods using electroretinography (ERG). In the absence of HCN1, rod responses are prolonged in dim light which altered the response to slow modulation of light intensity both at the level of retinal signaling and behavior. Under brighter intensities, cone-driven signaling was suppressed. To our surprise, conditional KO of HCN1 from mouse cones had no effect on cone-mediated signaling. We propose that Ih is dispensable in cones because of the high level of temporal control of cone phototransduction. Thus, HCN1 is required for cone-driven retinal signaling only indirectly by modulating the voltage response of rods to limit their output.SIGNIFICANCE STATEMENT Hyperpolarization gated hyperpolarization-activated cyclic nucleotide-gated 1 (HCN1) channels carry a feedback current that helps to reset light-activated photoreceptors. Using conditional HCN1 knock-out (KO) mice we show that ablating HCN1 from rods allows rods to signal in bright light when they are normally shut down. Instead of enhancing vision this results in suppressing cone signaling. Conversely, ablating HCN1 from cones was of no consequence. This work provides novel insights into the integration of rod and cone signaling in the retina and challenges our assumptions about the role of HCN1 in cones.

Targeted electric signal use for disease diagnostics and treatment is emerging as a healthcare game-changer. Besides arrhythmias, treatment-resistant epilepsy and chronic pain, blindness, and perhaps soon vision loss, could be among the pathologies that benefit from bioelectronic medicine. The electroretinogram (ERG) technique has long demonstrated its role in diagnosing eye diseases and early stages of neurodegenerative diseases. Conspicuously, ERG applications are all based on light-induced responses. However, spontaneous, intrinsic activity also originates in retinal cells. It is a hallmark of degenerated retinas and its alterations accompany obesity and diabetes. To the extent that variables extracted from the resting activity of the retina measured by ERG allow the predictive diagnosis of risk factors for type 2 diabetes. Here, we provided a comparison of the baseline characteristics of intrinsic oscillatory activity recorded by ERGs in mice, rats, and humans, as well as in several rat strains, and explore whether zebrafish exhibit comparable activity. Their pattern was altered in neurodegenerative models including the cuprizone-induced demyelination model in mice as well as in the Royal College of Surgeons (RCS–/–) rats. We also discuss how the study of their properties may pave the way for future research directions and treatment approaches for retinopathies, among others.

The electroretinogram (ERG) is a clinical test that records the retina's electrical response to light. Analysis of the ERG signal offers a promising way to study different retinal diseases and disorders. Machine learning-based methods are expected to play a pivotal role in achieving the goals of retinal diagnostics and treatment control. This study aims to improve the classification accuracy of the previous work using the combination of three optimal mother wavelet functions. We apply Continuous Wavelet Transform (CWT) on a dataset of mixed pediatric and adult ERG signals and show the possibility of simultaneous analysis of the signals. The modern Visual Transformer-based architectures are tested on a time-frequency representation of the signals. The method provides 88% classification accuracy for Maximum 2.0 ERG, 85% for Scotopic 2.0, and 91% for Photopic 2.0 protocols, which on average improves the result by 7.6% compared to previous work. [ABSTRACT FROM AUTHOR]

Clinical and genomic features of prostate cancer (PCa) vary considerably between Asian and Western populations. PTEN loss is the most frequent abnormality in intraductal carcinoma of the prostate (IDC‐P) in Western populations. However, its prevalence and significance in Asian populations have not yet been well studied. In the present study, we evaluated PTEN expression in IDC‐P in a Japanese population and its association with ERG expression. This study included 45 and 59 patients with PCa with and without IDC‐P, respectively, who underwent radical prostatectomy. PTEN loss was observed in 10 patients with PCa with IDC‐P (22%) and nine patients with PCa without IDC‐P (17%). ERG expression was relatively frequent in patients with PCa with PTEN loss, although a significant difference was not observed. The co‐occurrence of PTEN loss and ERG expression was observed in four patients with PCa with IDC‐P and one without IDC‐P. PTEN loss and ERG expression did not affect progression‐free survival, regardless of the presence of IDC‐P. The frequency of PTEN loss in IDC‐P is lower in Asian patients than in Western patients. Our results indicate that mechanisms underlying IDC‐P in Asian populations are different from those of Western populations. [ABSTRACT FROM AUTHOR]

Simple Summary: Prostate cancer is a malignancy with varying clinical outcomes, and monitoring renal function is crucial for patient care. Our study investigates the relationship between renal function and distinct molecular subtypes of prostate adenocarcinomas. We analyzed 72 patients with prostate cancer and chronic kidney disease who underwent radical prostatectomy. We categorized patients based on molecular markers and found that the ERG+/SPINK1+ subgroup had higher postoperative kidney disease stages and serum creatinine levels compared to the ERG+/SPINK1− subgroup, suggesting a connection between SPINK1 overexpression and kidney function. The HOXB13 −/TFF3+ subgroup exhibited higher preoperative serum creatinine levels and kidney disease stages than the HOXB13−/TFF3− subgroup, implying a role for TFF3 in kidney function. Furthermore, our study revealed links between kidney disease stages and prognostic grade groups in different molecular subtypes, highlighting the complex interplay between kidney function and tumor behavior. Our research underscores the importance of considering molecular subtypes in prostate cancer management. Prostate cancer is a prevalent malignancy in male patients, having diverse clinical outcomes. The follow-up of patients diagnosed with prostate cancer involves the evaluation of renal function, because its impairment reduces patient survival rates and adds complexity to their treatment and clinical care. This study aimed to investigate the relationship between renal function parameters and distinctive molecular subtypes of prostate adenocarcinomas, defined by the immunoexpression of the SPINK1, ERG, HOXB13, and TFF3 markers. The study group comprised 72 patients with prostate cancer and associated chronic kidney disease (CKD) who underwent radical prostatectomy. Histopathological, molecular, and renal parameters were analyzed. Patients were categorized based on ERG/SPINK1 and HOXB13/TFF3 status, and correlations with renal function and prognostic grade groups were assessed. The ERG+/SPINK1+ subgroup exhibited significantly higher postoperative CKD stages and serum creatinine levels compared to the ERG+/SPINK1− subgroup. This suggests an intricate relationship between SPINK1 overexpression and renal function dynamics. The HOXB13−/TFF3+ subgroup displayed higher preoperative serum creatinine levels and CKD stages than the HOXB13−/TFF3− subgroup, aligning with TFF3's potential role in renal function. Furthermore, the study revealed associations between CKD stages and prognostic grade groups in different molecular subtypes, pointing out an intricate interplay between renal function and tumor behavior. Although the molecular classification of prostate acinar ADK is not yet implemented, this research underscores the variability of renal function parameters in different molecular subtypes, offering potential insights into patient prognosis. [ABSTRACT FROM AUTHOR]

Hereditary retinal degeneration (RD) is often associated with excessive cGMP signalling in photoreceptors. Previous research has shown that inhibition of cGMP-dependent protein kinase G (PKG) can reduce photoreceptor loss in two different RD animal models. In this study, we identified a PKG inhibitor, the cGMP analogue CN238, which preserved photoreceptor viability and functionality in rd1 and rd10 mutant mice. Surprisingly, in explanted retinae, CN238 also protected retinal ganglion cells from axotomy-induced retrograde degeneration and preserved their functionality. Furthermore, kinase activity-dependent protein phosphorylation of the PKG target Kv1.6 was reduced in CN238-treated rd10 retinal explants. Ca2+-imaging on rd10 acute retinal explants revealed delayed retinal ganglion cell repolarization with CN238 treatment, suggesting a PKG-dependent modulation of Kv1-channels. Together, these results highlight the strong neuroprotective capacity of PKG inhibitors for both photoreceptors and retinal ganglion cells, illustrating their broad potential for the treatment of retinal diseases and possibly neurodegenerative diseases in general. [ABSTRACT FROM AUTHOR]

Objective: To explore the mechanisms of miR-196b affecting the progression of lung adenocarcinoma (LUAD). Methods: The expression level of miR-196b in LUAD tissues was analyzed through TCGA database. TargetScan was used to predict its downstream target genes, and dual-luciferase assay was performed to validate the predictions. qRT-PCR was used to detect the expression of miR-196b and ETS-related gene (ERG) in LUAD cell lines. MTT, scratch healing, and Transwell assays were used to respectively assess the changes in proliferation, migration, and invasion abilities of LUAD cells after different treatments. Results: miR196b was highly expressed in LUAD (P = 3.50e-17)and negatively regulated ERG. Overexpression of miR-196b promoted proliferation, migration, and invasion of LUAD cells (P < 0.05). Rescue experiments confirmed that miR196b/ERG regulatory axis can affect the proliferation, migration, and invasion of LUAD cells (P < 0.05). The molecular mechanism of miR-196b targeting ERG in promoting the progression of LUAD has potential significance for the development of new clinical treatment methods for LUAD. [ABSTRACT FROM AUTHOR]

Multimodal imaging and genetic testing allow sophisticated assessment of suspected inherited retinal disease. Given the availability of such technology, some question whether the full-field electrogram (ffERG) is needed anymore. In fact, a ffERG remains essential for certain clinical scenarios. The goal of this case-based review is to provide a clear understanding of what clinical situations warrant a ffERG. All practicing ophthalmologists should be familiar with this information. [ABSTRACT FROM AUTHOR]