The clinical landscape of Peyronie’s disease is everchanging. There has been growing interest in non-invasive therapeutic options that could assist patients with achieving a meaningful reduction in penile curvature without surgical intervention. These therapies are wide-ranging in terms of their mechanisms of action, efficacies, and short- and long-term safety profiles. Recently, an abundance of outcomes literature on longstanding and novel non-surgical treatment modalities has been published. For sexual medicine providers hoping to offer patients the most up-to-date and evidence-based treatments for the management of Peyronie’s disease, it can be challenging to gain a thorough understanding of this body of literature. In this clinical management review, the workup and current theories on the pathophysiology of Peyronie’s disease are reviewed, and the most recent outcomes data on the currently available non-surgical treatment modalities are presented. With an accurate understanding of the current landscape of Peyronie’s disease treatment, sexual health providers will be able to better evaluate and engage in evidence-based shared decision-making with their patients.
Lifelong learning without catastrophic forgetting (i.e., resiliency) possessed by human intelligence is entangled with sophisticated memory mechanisms in the brain, especially the long-term memory (LM) maintained by Hippocampi. To a certain extent, Transformers have emerged as the counterpart "Brain" of Artificial Intelligence (AI), and yet leave the LM component under-explored for lifelong learning settings. This paper presents a method of learning to grow Artificial Hippocampi (ArtiHippo) in Vision Transformers (ViTs) for resilient lifelong learning. With a comprehensive ablation study, the final linear projection layer in the multi-head self-attention (MHSA) block is selected in realizing and growing ArtiHippo. ArtiHippo is represented by a mixture of experts (MoEs). Each expert component is an on-site variant of the linear projection layer, which is maintained via neural architecture search (NAS) with the search space defined by four basic growing operationsskip, reuse, adapt, and new in lifelong learning. The LM of a task consists of two parts: the dedicated expert components (as model parameters) at different layers of a ViT learned via NAS, and the mean class-tokens (as stored latent vectors for measuring task similarity) associated with the expert components. For a new task, a hierarchical task-similarity-oriented exploration-exploitation sampling based NAS is proposed to learn the expert components. The task similarity is measured based on the normalized cosine similarity between the mean class-token of the new task and those of old tasks. The proposed method is complementary to prompt-based lifelong learningwith ViTs. In experiments, the proposed method is tested on the challenging Visual Domain Decathlon (VDD) benchmark and the recently proposed 5-Dataset benchmark. It obtains consistently better performance than the prior art with sensible ArtiHippo learned continually.
The cell cycle of Caulobacter crescentus involves the polar morphogenesis and an asymmetric cell division driven by precise interactions and regulations of proteins, which makes Caulobacter an ideal model organism for investigating bacterial cell development and differentiation. The abundance of molecular data accumulated on Caulobacter motivates system biologists to analyze the complex regulatory network of cell cycle via quantitative modeling. In this paper, We propose a comprehensive model to accurately characterize the underlying mechanisms of cell cycle regulation based on the study of: a) chromosome replication and methylation; b) interactive pathways of five master regulatory proteins including DnaA, GcrA, CcrM, CtrA, and SciP, as well as novel consideration of their corresponding mRNAs; c) cell cycle-dependent proteolysis of CtrA through hierarchical protease complexes. The temporal dynamics of our simulation results are able to closely replicate an extensive set of experimental observations and capture the main phenotype of seven mutant strains of Caulobacter crescentus. Collectively, the proposed model can be used to predict phenotypes of other mutant cases, especially for nonviable strains which are hard to cultivate and observe. Moreover, the module of cyclic proteolysis is an efficient tool to study the metabolism of proteins with similar mechanisms.
subgroups according to the onset of DM as early (<45 years old), average (45-65 years old), and late (>65 years old).RESULTS: A total of 185 patients were evaluated. Data collection parameters are shown in Table 1. Early onset DM correlated with the early development of PD (rho[0.52, p<0.001). Also, early onset DM correlated with the formation of penile plaque (rho[-0.18, p[0.03) and larger plaque size (rho [-0.35, p[0.03). An increase in HbA1c level after the initial diagnosis of PD positively correlated with the formation of penile plaque (rho[0.24, p[0.03) and penile deformity (rho[ 0.24, p[0.049).CONCLUSIONS: Our study suggested that early onset DM and a further increase in HbA1c levels after the PD diagnosis significantly impact the severity of PD. Revealing the mechanisms behind these findings will help us develop better management strategies in diabetic PD patients.
Per the Children's Oncology Group (COG) protocols, partial nephrectomy (PN) for Wilms tumor (WT) is reserved for bilateral tumors or lesions in solitary kidneys. Furthermore, most WTs are large masses that would not be amenable to partial nephrectomy. Unlike COG, the Societe Internationale d'Oncologie Pediatrique (SIOP) offers neoadjuvant chemotherapy (NAC) prior to surgical resection, allowing for tumor shrinkage. The Nephrometry score (NS) is a tool that was developed to assess the complexity of renal cell carcinoma, and thus the feasibility of partial nephrectomy. It relies on morphological features of tumors seen on cross-sectional imaging. The NS was however developed for renal cell carcinoma. Only one study to date has assessed Wilms tumors using the NS, showing that most are highly complex lesions not amenable to (PN). The goal of our study is to assess if NAC decreases the complexity of Wilms tumor using the NS.METHODS: We retrospectively identified patients with WT at our institution who received NAC (according to COG protocols). Preand post-treatment tumor volumes and NS were calculated by a single radiologist. For bilateral or multifocal tumors, the score was calculated for the most complex mass. NS was broken down into low, intermediate and high complexity groups. Rates of PN were stratified by NS score and by pre-operative variables. Statistical differences were assessed using paired t-tests and chi square tests.RESULTS: 54 patients were identified. The median pre-and post-treatment tumor volumes were 499 and 90 cm3, respectively (p<0.0001). Before NAC, NS was considered low, intermediate and high in 3.7%, 13% and 83.3% of patients, respectively. After NAC, the NS score was low, intermediate and high in 11.1%, 25.9% and 63% of patients. Fourteen tumors (26%) had their complexity downgraded. Overall rates of PN were 35% (n[19). There were statistically significant higher rates of PN for tumors with a low NS (83%) vs intermediate (64.3%) and high (14.7%) scores (p<0.0001). Among pre-operative variables such as age, sex, race, ethnicity, syndromic Wilms and stage, only female sex was statistically associated with higher rates of downgrading after NAC (36% vs 9.5% of males, p[0.028).CONCLUSIONS: The majority of WT are complex masses. Our data shows that NAC can reduce tumor complexity in 26% of cases, with more than half the patients with low or intermediate complexity WT undergoing successful PN. Further studies are needed to identify which patients with unilateral non-syndromic WT could benefit from NAC with the goal of nephron-sparing surgery.
Background-Allograft coronary atherosclerosis (TxCAD) is the leading cause of death after the first year after transplantation. TxCAD is believed to be a form of chronic rejection of the cardiac allografts. This study was undertaken to determine whether TxCAD could develop in the absence of a cellular alloimmune response. Methods and Results-Inbred lean Zucker rats (Ͼ26 generations) served as donors and recipients of the cardiac grafts.Donor hearts were explanted at 60 or 90 days. Explanted hearts were processed for coronary artery histological analysis. Cytokine expression was determined by reverse transcription-polymerase chain reaction, and the presence of T cells within the explanted hearts was evaluated by immunohistochemistry. Forty-six transplantations were made, and TxCAD developed in all but one of the transplanted hearts. Overall, one third of the vessels examined were affected by TxCAD, and in roughly half of these vessels, the disease was severe. Native hearts were free of atherosclerosis. Interleukin-2 was absent from the transplanted hearts, and T cells were present in minimal amounts (Ͻ1 per low-power field). Conclusions-TxCAD developed in the absence of a cellular alloimmune response in these genetically similar donors and recipients. The observed TxCAD was significant and comparable to what is found in rat allografting models.
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