Prioritizing disease candidate genes by a gene interconnectedness-based approach

<p>Abstract</p> <p>Background</p> <p>Genome-wide disease-gene finding approaches may sometimes provide us with a long list of candidate genes. Since using pure experimental approaches to verify all candidates could be expensive, a number of network-based methods have been developed to prioritize candidates. Such tools usually have a set of parameters pre-trained using available network data. This means that re-training network-based tools may be required when existing biological networks are updated or when networks from different sources are to be tried.</p> <p>Results</p> <p>We developed a parameter-free method, interconnectedness (ICN), to rank candidate genes by assessing the closeness of them to known disease genes in a network. ICN was tested using 1,993 known disease-gene associations and achieved a success rate of ~44% using a protein-protein interaction network under a test scenario of simulated linkage analysis. This performance is comparable with those of other well-known methods and ICN outperforms other methods when a candidate disease gene is not directly linked to known disease genes in a network. Interestingly, we show that a combined scoring strategy could enable ICN to achieve an even better performance (~50%) than other methods used alone.</p> <p>Conclusions</p> <p>ICN, a user-friendly method, can well complement other network-based methods in the context of prioritizing candidate disease genes.</p

Association Between Type I and II Diabetes With Gallbladder Stone Disease

Objective: To assess the association of type 1 diabetes (T1DM) and type 2 diabetes (T2DM) with the subsequent development of gallbladder stone disease (GSD).Setting: Cohort Study.Participants: We identified two study cohort groups to evaluate the association of T1DM and T2DM with the development of GSD. The first group comprised a T1DM cohort of 7015 patients aged ≤ 40 years and a non-diabetes cohort randomly matched with the study cohort (4:1). The second group comprised a T2DM cohort of 51,689 patients aged ≥20 years and a non-diabetes cohort randomly matched with the study cohort (1:1). All patients were studied from 1996 to the end of 2011 or withdrawal from the National Health Insurance program to determine the incidence of GSD.Results: Compared with patients without diabetes, those with T1DM had a decreased risk of GSD [adjusted hazard ratios (aHR) = 0.48, 95% confidence interval (CI) = 0.25–0.92]. Those with T2DM had an increased risk of GSD (aHR = 1.55, 95% CI = 1.41–1.69), after adjustment for age, sex, comorbidities, and number of parity. The relative risk of GSD in the T2DM cohort was higher than that in the non-diabetes cohort in each group of age, sex, and patients with or without comorbidity. However, the relative risk of GSD in the T1DM cohort was lower than that in the non-diabetes cohort only in the age group of 20–40 years.Conclusion: Our population-based cohort study reveals a strong association between T2DM and GSD. However, an inverse relationship exists between T1DM and GSD in patients aged 20–40 years

A novel method to identify cooperative functional modules: study of module coordination in the Saccharomyces cerevisiae cell cycle

<p>Abstract</p> <p>Background</p> <p>Identifying key components in biological processes and their associations is critical for deciphering cellular functions. Recently, numerous gene expression and molecular interaction experiments have been reported in <it>Saccharomyces cerevisiae</it>, and these have enabled systematic studies. Although a number of approaches have been used to predict gene functions and interactions, tools that analyze the essential coordination of functional components in cellular processes still need to be developed.</p> <p>Results</p> <p>In this work, we present a new approach to study the cooperation of functional modules (sets of functionally related genes) in a specific cellular process. A cooperative module pair is defined as two modules that significantly cooperate with certain functional genes in a cellular process. This method identifies cooperative module pairs that significantly influence a cellular process and the correlated genes and interactions that are essential to that process. Using the yeast cell cycle as an example, we identified 101 cooperative module associations among 82 modules, and importantly, we established a cell cycle-specific cooperative module network. Most of the identified module pairs cover cooperative pathways and components essential to the cell cycle. We found that 14, 36, 18, 15, and 20 cooperative module pairs significantly cooperate with genes regulated in early G1, late G1, S, G2, and M phase, respectively. Fifty-nine module pairs that correlate with Cdc28 and other essential regulators were also identified. These results are consistent with previous studies and demonstrate that our methodology is effective for studying cooperative mechanisms in the cell cycle.</p> <p>Conclusions</p> <p>In this work, we propose a new approach to identifying condition-related cooperative interactions, and importantly, we establish a cell cycle-specific cooperation module network. These results provide a global view of the cell cycle and the method can be used to discover the dynamic coordination properties of functional components in other cellular processes.</p

Moderate glucose control results in less negative nitrogen balances in medical intensive care unit patients: a randomized, controlled study

INTRODUCTION: Hyperglycemia and protein loss are common in critically ill patients. Insulin can be used to lower blood glucose and inhibit proteolysis. The impact of moderate insulin therapy on protein metabolism in critically ill patients has not been evaluated. We compared urinary nitrogen excretion, nitrogen balance, serum albumin concentrations, prealbumin concentrations, and clinical outcomes between patients receiving moderate insulin therapy (MIT) and conventional insulin therapy (CIT) in a medical ICU. METHODS: Patients were randomly divided into groups and treated with MIT (glucose target 120 to 140 mg/dl) or CIT (glucose target 180 to 200 mg/dl). Calories and protein intake were recorded each day. On days 3, 7 and 14, the 24-hour urinary nitrogen excretion, nitrogen balance, and serum albumin and prealbumin concentrations were measured. Clinical outcomes data were collected. RESULTS: A total of 112 medical ICU patients were included, with 55 patients randomized to the MIT group and 57 patients randomized to the CIT group. Patients treated with MIT showed a trend towards increased nitrogen balance (P = 0.070), significantly lower urinary nitrogen excretion (P = 0.027), and higher serum albumin (P = 0.047) and prealbumin (P = 0.001) concentrations than patients treated with CIT. The differences between the two groups were most significant on day 3, when all factors showed significant differences (P < 0.05). CONCLUSIONS: Moderate glucose control results in less negative nitrogen balances in medical ICU patients. Differences are more significant in the early stages compared with the late stages of critical illness. TRIAL REGISTRATION: ClinicalTrial.Gov NCT 0122714

The Relationship between Qi Deficiency, Cancer-related Fatigue and Quality of Life in Cancer Patients

AbstractBackgroundQi (氣 qì) refers to the vital energy of the body in Traditional Chinese medicines (TCM). Qi deficiency (氣虛 qì xū) is the most common symptom in cancer patients according to the concept of TCM. We hypothesized that cancer patients with Qi deficiency suffer from poor quality of life (QOL) and fatigue.MethodAmong the 256 registered cancer patients screened at our outpatient clinic, a total of 198 were enrolled. The inclusion criteria were (1) age between 18 and 70years, (2) cancer diagnosis confirmed by the professional physician, (3) being Chinese, and (4) Eastern Cooperative Oncology Group (ECOG) performance status rating (PSR)≤3. The major outcome is the difference in QOL score in cancer patients with and without Qi deficiency.ResultsThe initial results showed statistically significant differences in WHO-QOL scores in physical, psychological, and social domains between the groups with and without Qi deficiency as well as the groups with and without cancerrelated fatigue (CRF). All patients with CRF present were also diagnosed as Qi deficient. In addition, among the patients with no CRF, 39.9% (69/173) were diagnosed as suffering from Qi deficiency, which led to poor QOL.ConclusionsThe present study showed statistically significant difference in WHO-QOL scores in physical, psychological, and social domains between the groups with and without Qi deficiency as well as the groups with and without CRF. Cancer patients diagnosed with Qi deficiency or CRF have poor QOL. The concept of Qi deficiency in TCM might be applied to cancer health care

THE EFFECT OF INSULIN AND CARBOHYDRATE SUPPLEMENTATION ON GLYCOGEN REPLENISHMENT AMONG DIFFERENT HINDLIMB MUSCLES IN RATS FOLLOWING PROLONGED SWIMMING

In the present study we investigated the interactive effects of insulin and carbohydrate on glycogen replenishment in different rat hindlimb muscles. Forty male Sprague Dawley rats were assigned to 5 groups, including 1) sedentary control with carbohydrate supplement (2 g glucose · kg body wt-1), 2) sedentary rats with 16 hours recovery, carbohydrate and insulin (0.5 U · kg body wt-1), 3) swimming without recovery, 4) swimming with 16 hours recovery and carbohydrate supplement, and 5) swimming with 16 hours recovery, carbohydrate and insulin. The swimming protocol consisted of two 3 h swimming sections, which were separated by a 45 min rest. The insulin and carbohydrate were administered to the rats immediately after exercise. At the end of the experiment, the soleus (S), plantaris (P), quadriceps (Q) and gastrocnemius (G) were surgically excised to evaluate glycogen utilization and replenishment. We observed that glycogen utilization was significantly lower in G and Q than S and P during swimming (p <0.05), and S showed the greatest capacity of glycogen resynthesis after post-exercise recovery (p <0.05). In the sedentary state, the glycogen synthesis did not differ among hindlimb muscles during insulin and carbohydrate treatments. Interestingly, with insulin and carbohydrate, the glycogen resynthesis in S and P were significantly greater than in Q and G following post-exercise recovery (p <0.05). We therefore concluded that the soleus and plantaris are the primary working muscles during swimming, and the greatest glycogen replenishment capacity of the soleus during post-exercise recovery is likely due to its highest insulin sensitivity

Pulsed laser deposition of hexagonal GaN-on-Si(100) template for MOCVD applications

Growth of hexagonal GaN on Si(100) templates via pulsed laser deposition (PLD) was investigated for the further development of GaN-on-Si technology. The evolution of the GaN growth mechanism at various growth times was monitored by SEM and TEM, which indicated that the GaN growth mode changes gradually from island growth to layer growth as the growth time increases up to 2 hours. Moreover, the high-temperature operation (1000°C) of the PLD meant no significant GaN meltback occurred on the GaN template surface. The completed GaN templates were subjected to MOCVD treatment to regrow a GaN layer. The results of X-ray diffraction analysis and photoluminescence measurements show not only the reliability of the GaN template, but also the promise of the PLD technique for the development of GaN-on-Si technology

Mobile Edge Computing Platform Deployment in 4G LTE Networks: A Middlebox Approach

This paper has been presented at : USENIX Workshop on Hot Topics in Edge Computing (Hot Edge '18)Low-latency demands for cellular networks have at-tracted much attention. Mobile edge computing (MEC), which deploys a cloud computing platform at the edge closer to mobile users, has been introduced as an enabler of low-latency performance in 4G and 5G networks. In this paper, we propose an MEC platform deployment so-lution in 4G LTE networks using a middlebox approach. It is standard-compliant and transparent to existing cel-lular network components, so they need not be modified. The MEC middlebox sits on the S1 interface, which con-nects an LTE base station to its core network, and does traffic filtering, manipulation and forwarding. It enables the MEC service for mobile users by hosting application servers. Such middlebox approach can save deployment cost and be easy to install. It is different from other stud-ies that require modifications on base stations or/and core networks. We have confirmed its viability through a pro-totype based on the OpenAirInterface cellular platform.We thank our shepherd Weisong Shi for his help, and also thank the anonymous reviewers for their valuable comments on improving this paper. This work was partially supported by the Ministry of Science and Technology, Taiwan, under grant numbers 106-2622-8-009-017 and 106-2218-E-009-018, and by the H2020 collaborative Europe/Taiwan research project 5G-CORAL (grant number 761586)