Selecting additional tag SNPs for tolerating missing data in genotyping

BACKGROUND: Recent studies have shown that the patterns of linkage disequilibrium observed in human populations have a block-like structure, and a small subset of SNPs (called tag SNPs) is sufficient to distinguish each pair of haplotype patterns in the block. In reality, some tag SNPs may be missing, and we may fail to distinguish two distinct haplotypes due to the ambiguity caused by missing data. RESULTS: We show there exists a subset of SNPs (referred to as robust tag SNPs) which can still distinguish all distinct haplotypes even when some SNPs are missing. The problem of finding minimum robust tag SNPs is shown to be NP-hard. To find robust tag SNPs efficiently, we propose two greedy algorithms and one linear programming relaxation algorithm. The experimental results indicate that (1) the solutions found by these algorithms are quite close to the optimal solution; (2) the genotyping cost saved by using tag SNPs can be as high as 80%; and (3) genotyping additional tag SNPs for tolerating missing data is still cost-effective. CONCLUSION: Genotyping robust tag SNPs is more practical than just genotyping the minimum tag SNPs if we can not avoid the occurrence of missing data. Our theoretical analysis and experimental results show that the performance of our algorithms is not only efficient but the solution found is also close to the optimal solution

Exploring the underlying mechanisms of obesity and diabetes and the potential of Traditional Chinese Medicine: an overview of the literature

Obesity and diabetes are closely related metabolic disorders that have become major public health concerns worldwide. Over the past few decades, numerous studies have explored the underlying mechanisms of these disorders and identified various risk factors, including genetics, lifestyle, and dietary habits. Traditional Chinese Medicine (TCM) has been increasingly recognized for its potential to manage obesity and diabetes. Weight loss is difficult to sustain, and several diabetic therapies, such as sulfonylureas, thiazolidinediones, and insulin, might make it harder to lose weight. While lifestyle changes should be the primary approach for people interested in lowering weight, drugs are also worth investigating. Since some of the newer glucose-lowering medications that cause weight loss, such as glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and sodium-glucose cotransporter 2 inhibitors (SGLT2i), are additionally utilized or are under consideration for use as anti-obesity drugs, the frontier between glucose-lowering medication and weight loss drugs appears to be shifting. This review provides an overview of the literature on the underlying mechanisms of obesity and diabetes and the prospect of TCM in their management. We discuss the various TCM interventions, including acupuncture, herbal medicine, and dietary therapy, and their effects on metabolic health. We also highlight the potential of TCM in regulating gut microbiota, reducing inflammation, and improving insulin sensitivity. The findings suggest that TCM may provide a promising approach to preventing and managing obesity and diabetes. However, further well-designed studies are needed to confirm the efficacy and safety of TCM interventions and to elucidate their underlying mechanisms of action

The impact of perioperative red blood cell transfusion on the prognosis of colorectal cancer

BackgroundThere is no consensus on the effect of red blood cell transfusion on colorectal cancer (CRC). This study examined the impact of perioperative red blood cell transfusion on postoperative complications, recurrence, and mortality in patients with CRC.MethodsIn this retrospective cohort study, 219 CRC patients admitted to Chongqing Emergency Medical Center, and Chongqing University Central Hospital from 2008 to 2019 were divided into transfusion (n = 75) and non-transfusion (n = 144) groups. Univariate and multivariate Logistic regression analysis were used to analyze the effects of blood transfusion on the severity of postoperative complications in patients with CRC, and univariate and multivariate Cox regression was performed to analyze the effects of blood transfusion on postoperative death and recurrence.ResultsTwenty-two (29.33%) patients in the transfusion group were intermediate or advanced severity of postoperative complications, 31 (41.33%) patients died in the transfusion group, and 55 (73.33%) patients occurred recurrence of the CRC, with the median follow-up time being 24.57(14.50,36.37) months. Our result showed that perioperative red blood cell transfusion was associated with an increased risk of intermediate or advanced severity of postoperative complications in CRC patients [odds ratio (OR) = 3.368, 95% CI, 1.146–9.901]. And perioperative red blood cell transfusion increased the risk of postoperative death [hazard ratio (HR) = 2.747, 95% CI, 1.048–7.205] and recurrence in patients with CRC (HR = 2.168, 95% CI, 1.192–3.943).ConclusionOur finding demonstrated that perioperative red blood cell transfusion was associated with severity of complications, recurrence, and death in CRC patients. However, further studies are still needed to confirm the adverse effects of red blood cell transfusions in CRC patients

Temperature-Sensitive Nanocapsules for Controlled Drug Release Caused by Magnetically Triggered Structural Disruption

Self-assembled nanocapsules containing a hydrophilic core and a crosslinked yet thermosensitive shell have been successfully prepared using poly(ethylene-oxide)-poly(propylene-oxide)-poly(ethylene-oxide) block copolymers, 4-nitrophenyl chloroformate, gelatin, and 1-ethyl-3-(3- dimethylaminopropyl) carbodiimide. The core is further rendered magnetic by incorporating iron oxide nanoparticles via internal precipitation to enable externally controlled actuation under magnetic induction. The spherical nanocapsules exhibit a hydrophilic-to-hydrophobic transition at a characteristic but tunable temperature reaching 40ºC, triggering a size contraction and shrinkage of the core. The core content experiences very little leakage at 25ºC, has a half life about 5 h at 45ºC, but bursts out within a few minutes under magnetic heating due to iron oxide coarsening and core/shell disruption. Such burst-like response may be utilized for controlled drug release as illustrated here using a model drug Vitamin B12

An Integrated Bus and Taxi Routes for a Mobile Trip Planning System

With the popular usage of Google Maps and smart phones, more and more people are using smart phones to surf and inquire about travel information. As a result, every major city plans to push the existing online public transportation trip planning system beyond traditional computer users to mobile phone users. The trip planning system is based on the starting and ending points that a user inputs, and guides the user to take a bus or metro through an electronic map interface. The system usually provides different kind of alternative travel routes with the estimated time of arrival. However, people who use the public transport system may encounter some uncertainties, such as long waiting times, long routes, long walking distances, etc. In each big city, the taxi is a universal transport vehicle which is available at almost anytime, anywhere. Taxis can save passengers’ walking distance and travel time with a deficit of high cost. Therefore, we design a trip planning system to unify the Taipei public transportation system with taxis. The users can inquire of a travel route through the mobile phones. This system uses Google Maps as a base map. The users assign an upper limit of fare which they are willing to pay. The system will balance between travel time and travel cost to obtain a route which may combine usage of the bus and taxi. Because of the high density of bus stations in Taipei city, the route search may consume a lot of system resources. We propose an improvement method to eliminate some intermediate bus stations in route search processing

Reduction in antioxidant enzyme expression and sustained inflammation enhance tissue damage in the subacute phase of spinal cord contusive injury

<p>Abstract</p> <p>Background</p> <p>Traumatic spinal cord injury (SCI) forms a disadvantageous microenvironment for tissue repair at the lesion site. To consider an appropriate time window for giving a promising therapeutic treatment for subacute and chronic SCI, global changes of proteins in the injured center at the longer survival time points after SCI remains to be elucidated.</p> <p>Methods</p> <p>Through two-dimensional electrophoresis (2DE)-based proteome analysis and western blotting, we examined the differential expression of the soluble proteins isolated from the lesion center (LC) at day 1 (acute) and day 14 (subacute) after a severe contusive injury to the thoracic spinal cord at segment 10. In situ apoptotic analysis was used to examine cell apoptosis in injured spinal cord after adenoviral gene transfer of antioxidant enzymes. In addition, administration of chondroitinase ABC (chABC) was performed to analyze hindlimb locomotor recovery in rats with SCI using Basso, Beattie and Bresnahan (BBB) locomotor rating scale.</p> <p>Results</p> <p>Our results showed a decline in catalase (CAT) and Mn-superoxide dismutase (MnSOD) found at day 14 after SCI. Accordingly, gene transfer of SOD was introduced in the injured spinal cord and found to attenuate cell apoptosis. Galectin-3, β-actin, actin regulatory protein (CAPG), and F-actin-capping protein subunit β (CAPZB) at day 14 were increased when compared to that detected at day 1 after SCI or in sham-operated control. Indeed, the accumulation of β-actin⁺immune cells was observed in the LC at day 14 post SCI, while most of reactive astrocytes were surrounding the lesion center. In addition, chondroitin sulfate proteoglycans (CSPG)-related proteins with 40-kDa was detected in the LC at day 3-14 post SCI. Delayed treatment with chondroitinase ABC (chABC) at day 3 post SCI improved the hindlimb locomotion in SCI rats.</p> <p>Conclusions</p> <p>Our findings demonstrate that the differential expression in proteins related to signal transduction, oxidoreduction and stress contribute to extensive inflammation, causing time-dependent spread of tissue damage after severe SCI. The interventions by supplement of anti-oxidant enzymes right after SCI or delayed administration with chABC can facilitate spinal neural cell survival and tissue repair.</p

Reduction in antioxidant enzyme expression and sustained inflammation enhance tissue damage in the subacute phase of spinal cord contusive injury

<p>Abstract</p> <p>Background</p> <p>Traumatic spinal cord injury (SCI) forms a disadvantageous microenvironment for tissue repair at the lesion site. To consider an appropriate time window for giving a promising therapeutic treatment for subacute and chronic SCI, global changes of proteins in the injured center at the longer survival time points after SCI remains to be elucidated.</p> <p>Methods</p> <p>Through two-dimensional electrophoresis (2DE)-based proteome analysis and western blotting, we examined the differential expression of the soluble proteins isolated from the lesion center (LC) at day 1 (acute) and day 14 (subacute) after a severe contusive injury to the thoracic spinal cord at segment 10. In situ apoptotic analysis was used to examine cell apoptosis in injured spinal cord after adenoviral gene transfer of antioxidant enzymes. In addition, administration of chondroitinase ABC (chABC) was performed to analyze hindlimb locomotor recovery in rats with SCI using Basso, Beattie and Bresnahan (BBB) locomotor rating scale.</p> <p>Results</p> <p>Our results showed a decline in catalase (CAT) and Mn-superoxide dismutase (MnSOD) found at day 14 after SCI. Accordingly, gene transfer of SOD was introduced in the injured spinal cord and found to attenuate cell apoptosis. Galectin-3, β-actin, actin regulatory protein (CAPG), and F-actin-capping protein subunit β (CAPZB) at day 14 were increased when compared to that detected at day 1 after SCI or in sham-operated control. Indeed, the accumulation of β-actin⁺immune cells was observed in the LC at day 14 post SCI, while most of reactive astrocytes were surrounding the lesion center. In addition, chondroitin sulfate proteoglycans (CSPG)-related proteins with 40-kDa was detected in the LC at day 3-14 post SCI. Delayed treatment with chondroitinase ABC (chABC) at day 3 post SCI improved the hindlimb locomotion in SCI rats.</p> <p>Conclusions</p> <p>Our findings demonstrate that the differential expression in proteins related to signal transduction, oxidoreduction and stress contribute to extensive inflammation, causing time-dependent spread of tissue damage after severe SCI. The interventions by supplement of anti-oxidant enzymes right after SCI or delayed administration with chABC can facilitate spinal neural cell survival and tissue repair.</p

Prevention of Dental Damage and Improvement of Difficult Intubation Using a Paraglossal Technique With a Straight Miller Blade

Patients with diseased teeth, or those who are difficult to intubate, have a higher risk of dental injury during laryngoscopy. We report 3 cases of smooth endotracheal intubation using a paraglossal technique with a straight Miller blade in patients with poor dentition. Three patients with poor dentition were scheduled to undergo surgery under general anesthesia. All patients presented with extremely loose upper central incisors and had lost the other right upper teeth, while micrognathia and prominent, loose upper incisors were noted in 1 case. We elected to use a straight Miller blade using a paraglossal approach. A nasopharyngeal airway was inserted after induction of general anesthesia to facilitate mask ventilation and prevent air leakage from the mask. The Miller blade was then inserted from the right corner of the mouth, avoiding contact with the vulnerable incisors, and advanced along the groove between the tongue and tonsil. The endotracheal tube was subsequently smoothly inserted after obtaining a grade 1 Cormack and Lehane view without dental trauma in all 3 cases. Direct laryngoscopy using the paraglossal straight blade technique avoids dental damage in patients with mobile upper incisors and no right maxillary molars. It is a practical alternative method that differs from the traditional Macintosh laryngoscope in patients with a high risk of dental injury during the procedure. This technique, which provides an improved view of the larynx, might also be helpful with patients in whom intubation is difficult