Response time decides how fast a gene can react against an external signal at the transcription level in a signalling cascade. The steady state protein levels of the responding genes decide the coupling between two consecutive members of a signalling cascade. A negative autoregulatory loop (NARL) present in a transcription factor network can speed up the response time of the regulated gene at the cost of reduced steady state protein level. We present here a multi NARL motif which can be tuned for both the steady state protein level as well as response time in the required direction. Remarkably, there exists an optimum Hill coefficient nop t ≅ 4 at which the response time of the NARL motif is at minimum. When the Hill coefficient is n less then nopt , then under strong binding conditions, one can raise the steady state protein level by increasing the gene copy number with almost no change in the response time of the multi NARL motif. Using detailed computational analysis, we show that the coupled multi NARL and positive auto regulatory loop (PARL) motifs can act as an oscillator as well as decision making component which are robust against extrinsic fluctuations in the control parameters. We further demonstrate that the period of oscillation of the coupled multi NARL-PARL dual feedback oscillator can also be fine-tuned by the gene copy number apart from the inducer concentration. We finally demonstrate robustness of bistable dual feedback decision making motifs with multi autoregulatory loop component.
Hyphema is a sequela of ocular trauma and can be associated with significant morbidity. Management of this condition is variable and can depend on individual institutional guidelines. We aimed to summarize current practices in hyphema management across ophthalmological institutions worldwide.
A cross-sectional online survey was conducted across North America, Asia, South America, Africa, Europe, and Australia from August 2020 to January 2021. The survey assessed the existing practices in the management of hyphema at each institution.
For layered hyphema, topical steroids were routinely administered by 34 (of 36 respondents, 94.4%) institutions, of which prednisolone was the preferred choice (n = 32, 88.9%). https://www.selleckchem.com/products/kartogenin.html Topical cycloplegics were used at 34 (94.4%) institutions. No institution reported routine use of antifibrinolytics. Head elevation was the most deployed procedure to promote hyphema reabsorption (n = 31, 86.3%), followed by partial bed rest (n = 21, 58.3%). The majority of institutions (n = 25, 69.4ing on hyphema management. Additionally, areas of consensus can be used as foundations for future standard of care investigations.Multilevel programming is widely applied to solve decentralized decision-making problems. In practice, indeterminacies are presented in these problems due to volatile factors or emergencies. As a type of indeterminacy, uncertainty is introduced in multilevel programming. For resolving multilevel programming problems with uncertain parameters, this paper constructs the uncertain expected value multilevel programming model and chance-constrained multilevel programming. Then, these models are converted to their equivalent forms. Moreover, the Stackelberg-Nash equilibrium solutions are obtained by using a genetic algorithm. Finally, these models are applied to the omni-channel vehicle routing problem, and a numerical experiment is given. The numerical experiment shows that the established models can optimize the distribution efficiency by coordinating the interests of decision-makers.
Multi-omics data integration facilitates collecting richer understanding and perceptions than separate omics data. Various promising integrative approaches have been utilized to analyze multi-omics data for biomedical applications, including disease prediction and disease subtypes, biomarker prediction, and others.
In this paper, we introduce a multi-omics data integration method that is constructed using the combination of gene similarity network (GSN) based on uniform manifold approximation and projection (UMAP) and convolutional neural networks (CNNs). The method utilizes UMAP to embed gene expression, DNA methylation, and copy number alteration (CNA) to a lower dimension creating two-dimensional RGB images. Gene expression is used as a reference to construct the GSN and then integrate other omics data with the gene expression for better prediction. We used CNNs to predict the Gleason score levels of prostate cancer patients and the tumor stage in breast cancer patients.
The model proposed near perfection with accuracy above 99% with all other performance measurements at the same level. The proposed model outperformed the state-of-art iSOM-GSN model that constructs the GSN map based on the self-organizing map.
The results show that UMAP as an embedding technique can better integrate multi-omics maps into the prediction model than SOM. The proposed model can also be applied to build a multi-omics prediction model for other types of cancer.
The results show that UMAP as an embedding technique can better integrate multi-omics maps into the prediction model than SOM. The proposed model can also be applied to build a multi-omics prediction model for other types of cancer.
Infections due to carbapenem-resistant
(CRE) are associated in patients with urinary catheters alarming rate of emergency status. The aim of this study is to investigate the molecular causes of carbapenem resistance among UPEC as well as antimicrobial resistance trends. Additionally, the potential of isolates to produce biofilms, in addition to their clonal and genetic diversity, was investigated.
. A cross-sectional study was accomplished on a collection of 76 non-duplicate UPEC isolates obtained from CAUTIs from May 2021 to September 2021. The modified carbapenem inactivation method (mCIM) and EDTA-modified carbapenem inactivation method (eCIM) test was performed for the detection of carbapenemase and metallo-beta-lactamase activity. Also, the presence of carbapenemase genes was determined using PCR assays. In 96-well microtiter plates, biofilm development was evaluated. ERIC-PCR was used to investigate the clonal and genetic variety of isolates.
A total of 76 confirmed UPEC isolates were obtained MDR and carbapenemase-producing isolates among the UPEC strain in this investigation is concerning. Moreover, the bla NDM was the most frequent cause of producing metallo-beta-lactamase and carbapenemase. Also, analysis revealed a partial genetic similarity among the studied isolates, indicating that the same UPEC clones may have spread to other hospital units.
The study aimed to investigate the clinical epidemiological data and the survival rate of maintenance hemodialysis patients with tunneled cuffed central venous catheters (TCCs) in a single hemodialysis center in China.
We retrospectively investigated the general clinical characteristics (including sex, age, primary causes, and catheter outcome) of 316 patients undergoing maintenance hemodialysis (MHD) via TCC for >3 months at Wannan Medical College Affiliated Yijishan Hospital, Wuhu, China, from July 2011 to June 2021. The long-term survival rate of the catheters was determined by Kaplan-Meier survival analyses.
A total of 316 patients (137 males, 179 females) were included, with a mean age of 65.0 ± 15.5 years. The right internal jugular vein was the most commonly used central vein, accounting for 89.1% of catheterizations. After censoring for noncatheter-related events leading to the removal of the catheter, the mean survival time of the TCCs was 26.2 ± 19.8 smonths and the median survival time was 58.0 (95% CI, 54.0-62.0) months. Seventy patients had catheter loss-of-function events, with an incidence of 22.2%. Moreover, 97.3% of TCCs survived 1 year and 43.3% survived 5 years, respectively. The sex and age of the patients were not related to the survival rate (
> 0.05). There were also no statistical differences between the primary diseases of patients and the survival rate of TCCs (
> 0.05).
In this study, we provide evidence of the mean TCC survival time beyond 2 years. We found that TCC is an effective alternative for MHD patients with poor vessel status or limited survival time or become a bridge waiting for arteriovenous fistula to mature, regardless of age, sex, and primary diseases.
In this study, we provide evidence of the mean TCC survival time beyond 2 years. We found that TCC is an effective alternative for MHD patients with poor vessel status or limited survival time or become a bridge waiting for arteriovenous fistula to mature, regardless of age, sex, and primary diseases.
There have been no fully validated tools for the rapid identification of surgical patients at risk of intraoperative hypothermia. The objective of this study was to validate the performance of a previously established prediction model in estimating the risk of intraoperative hypothermia in a prospective cohort.
In this observational study, consecutive adults scheduled for elective surgery under general anesthesia were enrolled prospectively at a tertiary hospital between September 4, 2020, and December 28, 2020. An intraoperative hypothermia risk score was calculated by a mobile application of the prediction model. A wireless axillary thermometer was used to continuously measure perioperative core temperature as the reference standard. The discrimination and calibration of the model were assessed, using the area under the receiver operating characteristic curve (AUC), Hosmer-Lemeshow goodness-of-fit test, and Brier score.
Among 227 participants, 99 (43.6%) developed intraoperative hypothermia, and 10 (4ture perioperative temperature management.
Older people and people with dementia experience a high prevalence of multiple health conditions. The terms 'comorbidity' and 'multimorbidity' are often used interchangeably to describe this, however there are key conceptual differences between these terms and their definitions. This has led to issues in the validity and comparability of research findings, potentially inappropriate intervention development and differences in quality of health care.
To review how the terms 'comorbidity' and 'multimorbidity' are defined within peer-reviewed dementia research and propose an operational framework.
A scoping review of definitions within dementia research was carried out. Searches took place across five databases Academic Search Premier, CINAHL Complete, MEDLINE, PsycARTICLES and PsycINFO. PRISMA-ScR guidelines were followed.
Content analysis revealed five key themes, showing significant overlap and inconsistencies from both within, and between, the comorbidity and multimorbidity definitions; 1. Number of cd. A syndemic framework could be a useful tool for researchers, clinicians and policy makers to consider a more holistic picture of a person with dementia's health and wellbeing.
Coronavirus disease 2019 (COVID-19) has caused a spike in newly diagnosed diabetes mellitus (NDDM). NDDM and COVID-19 infection are not well established as a cause-and-effect relationship; hence, the present review aims to define the underlying causes and consequences of COVID-19 infection in relation to the condition.
β-Cells are infiltrated by SARS-CoV-2, causing glycometabolic dysfunction and insulin dysregulation. The disease causes systemic inflammation and pro-inflammatory cytokines, as well as hormonal changes that lead to insulin resistance and hyperglycemia that are difficult to manage. As a result of NDDM, complications related to COVID-19 infection become more severe.
NDDM related to COVID-19 infection complicates hospitalization outcomes and adversely affects quality of life in patients. There are many possible causes and consequences associated with NDDM, but for establishing preventive measures and treatments for NDDM, more evidence regarding its epidemiology, physiopathology, etiology, and nutritional aspects is required.