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Abstract Background Septicemia that leads to ocular involvement mostly presents as endophthalmitis or panophthalmitis. Contrarily, septicemia without intraocular involvement, known as hematogenous orbital cellulitis (HOC), involves only the orbit and is an extremely rare complication of septicemia and a rare type of orbital cellulitis. Case presentation Four male patients with septicemia presented with orbital involvement without intraocular infection were described in this study. They were 22 (case 1), 15 (case 2), 79 (case 3), and 30 (case 4) years old, with a mean age of 29.75 years. All patients were immunocompromised except for case 2. Cases 1 and 3 had a history of steroid use, whereas case 4 was in a post-chemotherapy myelosuppression phase. Septicemia in case 1 was community-acquired, cases 3 and 4 were hospital-acquired, and case 2 was secondary to acne squeezing. Blood cultures from cases 1, 2, and 3 were positive for Candida albicans, methicillin-resistant Staphylococcus aureus, and Klebsiella pneumoniae, respectively. Case 4 had negative cultures; however, next-generation sequencing reported the presence of Enterococcus faecalis and Rhizopus oryzae. Case 1 had right eye involvement, and both eyes were involved in the other three cases. According to Chandler’s classification, case 1 was type 2, case 2 was type 2 (OD) and type 4 (OS), and cases 3 and 4 were type 1 orbital infections. All patients had eyelids erythema, and cases 1 and 2 had mildly decreased visual acuity, proptosis, and painful and restricted ocular motility. Hospital stays ranged from 13 to 43 days (mean, 24 days). All patients received systemic antibiotic therapy based on drug sensitivity and next-generation sequencing results, in combination with multidisciplinary treatment, resulting in complete recovery of ocular and systemic signs and symptoms; no ocular surgical interventions were performed. Extraocular muscle palsy was the last symptom to resolve. Conclusion HOC is predominantly seen in immunocompromised individuals with a high proportion of hospital-acquired infections and positive cultures for pathogens. Infection control using systemic antibiotics targeted at the causative organism guarantees a favorable prognosis.

Abstract Background Phantom limb pain (PLP) is a prevalent problem for children after amputation because of the chemotherapy treatment. Gabapentin is a potential option to manage PLP after amputation in pediatric oncology. However, no systematic review specifically investigated this topic. Thus, this study aims to appraise the efficacy and safety of gabapentin for post-amputation PLP in pediatric oncology. Methods Electronic databases (Cochrane Library, MEDLINE, EMBASE, Web of Science, CINAHL, PsychINFO, Scopus, WANGFANG, and Chinese Biomedical Literature Database) will be systematically searched from the beginning to the present without limitations to publication status and language. Primary outcome is pain intensity. Secondary outcomes are analgesic drug consumption, sleep quality, depression, anxiety, health-related quality of life, and adverse events. The treatment effect of all dichotomous outcome data will be estimated as risk ratio and 95% confidence intervals (CIs) and that of continuous outcome data will be calculated as mean difference or standardized mean difference and 95% CIs. Methodological quality of randomized controlled trials (RCTs) will be assessed using Cochrane risk of bias tool and that of case-controlled studies (CCSs) will be appraised using Newcastle-Ottawa Tool. Statistical analysis will be conducted using RevMan 5.3 software. Discussion This study will summarize up-to-date high-quality RCTs and CCSs to assess the efficacy and safety of gabapentin for PLP after amputation in pediatric oncology. The findings of this study will help to determine whether or not gabapentin is effective and safe for children with PLP after amputation. Systematic review registration INPLASY202060090

Adaptive gradient algorithms have been successfully used in deep learning. Previous work reveals that adaptive gradient algorithms mainly borrow the moving average idea of heavy ball acceleration to estimate the first- and second-order moments of the gradient for accelerating convergence. However, Nesterov acceleration which uses the gradient at extrapolation point can achieve a faster convergence speed than heavy ball acceleration in theory. In this article, a new optimization algorithm which combines adaptive gradient algorithm with Nesterov acceleration by using a look-ahead scheme, called NALA, is proposed for deep learning. NALA iteratively updates two sets of weights, i.e., the 'fast weights' in its inner loop and the 'slow weights' in its outer loop. Concretely, NALA first updates the fast weights k times using Adam optimizer in the inner loop, and then updates the slow weights once in the direction of Nesterov's Accelerated Gradient (NAG) in the outer loop. We compare NALA with several popular optimization algorithms on a range of image classification tasks on public datasets. The experimental results show that NALA can achieve faster convergence and higher accuracy than other popular optimization algorithms. [ABSTRACT FROM AUTHOR]

Aims Previous studies suggest that small intestinal bacterial overgrowth (SIBO) is associated with type 2 diabetes. However, few studies have evaluated the association between SIBO and beta-cell function in type 2 diabetes. The aim of this study was to evaluate whether beta-cell function was associated with SIBO. Materials and methods One hundred four patients with type 2 diabetes were included in this study. Based on the presence of SIBO, the patients were divided into SIBO-positive and SIBO-negative groups. Oral glucose tolerance tests were performed. Insulin sensitivity was measured using 1/homeostasis model assessment of insulin resistance (1/HOMA-IR) and the insulin sensitivity index (ISIM). Insulin release was calculated by HOMA-β, early-phase insulin secretion index InsAUC 30 /GluAUC 30 , and total-phase insulin secretion index InsAUC 120 /GluAUC 120 . Results Compared with the SIBO-negative group, patients in the SIBO-positive group showed a higher glucose level at 120 minutes, HbA1c, 1/HOMA-IR, and ISIM and a lower HOMA-β level, early-phase InsAUC 30 /GluAUC 30 , and total-phase InsAUC 120 /GluAUC 120 . Multiple linear regression analysis showed that body mass index, glucose at 0 minutes, and SIBO were independently associated with the early-phase and total-phase insulin secretion. Conclusion SIBO may be involved in lower levels of insulin release and worse glycemic control.

Endocrine resistance is a major obstacle to hormonal therapy for breast cancers. Although reduced expression of estrogen receptor-α (ER-α) is a known contributing factor to endocrine resistance, the mechanism of ER-α downregulation in endocrine resistance is still not fully understood. Here we report that CUE domain-containing protein-2 (CUEDC2), a ubiquitin-binding motif-containing protein, is a key factor in endocrine resistance in breast cancer. We show that CUEDC2 modulates ER-α protein stability through the ubiquitin-proteasome pathway. Through the study of specimens from a large cohort of subjects with breast cancer, we found a strong inverse correlation between CUEDC2 and ER-α protein expression. Notably, subjects with tumors that highly expressed CUEDC2 had poor responsiveness to tamoxifen treatment and high potential for relapse. We further show that ectopic CUEDC2 expression impaired the responsiveness of breast cancer cells to tamoxifen. Therefore, our findings suggest that CUEDC2 is a crucial determinant of resistance to endocrine therapies in breast cancer., The CUE domains are small, moderately conserved ubiquitin-binding domains of ~40 amino acids; they are found in a variety of eukaryotic proteins (1,2). These proteins are involved in the recognition [...]

Activating mutations in Ras proteins are present in about 30% of human cancers. Despite tremendous progress in the study of Ras oncogenes, many aspects of the molecular mechanisms underlying Ras-induced tumorigenesis remain unknown. Through proteomics analysis, we previously found that the protein Gankyrin, a known oncoprotein in hepatocellular carcinoma, was upregulated during Ras-mediated transformation, although the functional consequences of this were not clear. Here we present evidence that Gankyrin plays an essential role in Ras-initiated tumorigenesis in mouse and human cells. We found that the increased Gankyrin present following Ras activation increased the interaction between the RhoA GTPase and its GDP dissociation inhibitor RhoGDI, which resulted in inhibition of the RhoA effector kinase Rho-associated coiled coil-containing protein kinase (ROCK). Importantly, Gankyrin-mediated ROCK inhibition led to prolonged Akt activation, a critical step in activated Ras-induced transformation and tumorigenesis. In addition, we found that Gankyrin is highly expressed in human lung cancers that have Ras mutations and that increased Gankyrin expression is required for the constitutive activation of Akt and tumorigenesis in these lung cancers. Our findings suggest that Gankyrin is a key regulator of Ras-mediated activation of Akt through inhibition of the downstream RhoA/ROCK pathway and thus plays an essential role in Ras-induced tumorigenesis., Introduction Carcinogenesis involves sequential mutations in genes that play key roles in the control of cell growth and proliferation (1). These mutations usually lead to either the loss of tumor [...]