Predicting adverse drug effects: A heterogeneous graph convolution network with a multi-layer perceptron approach.

We apply a heterogeneous graph convolution network (GCN) combined with a multi-layer perceptron (MLP) denoted by GCNMLP to explore the potential side effects of drugs. Here the SIDER, OFFSIDERS, and FAERS are used as the datasets. We integrate the drug information with similar characteristics from the datasets of known drugs and side effect networks. The heterogeneous graph networks explore the potential side effects of drugs by inferring the relationship between similar drugs and related side effects. This novel in silico method will shorten the time spent in uncovering the unseen side effects within routine drug prescriptions while highlighting the relevance of exploring drug mechanisms from well-documented drugs. In our experiments, we inquire about the drugs Vancomycin, Amlodipine, Cisplatin, and Glimepiride from a trained model, where the parameters are acquired from the dataset SIDER after training. Our results show that the performance of the GCNMLP on these three datasets is superior to the non-negative matrix factorization method (NMF) and some well-known machine learning methods with respect to various evaluation scales. Moreover, new side effects of drugs can be obtained using the GCNMLP.

High sugar-sweetened beverage intake frequency is associated with smoking, irregular meal intake and higher serum uric acid in Taiwanese adolescents.

Types of sugar-sweetened beverages (SSB) can differ greatly between countries, with greater consumption of sweetened tea in Asia. This study aimed to understand changes in SSB consumption by adolescents in Taiwan over 18 years and their association with demographic characteristics and clinical outcome. This study used survey data from the 1993-1996 and 2010-2011 Nutrition and Health Surveys in Taiwan. Participants were high school students aged 13 to 18 years. Data were weighted and analysed using SUDAAN 11.0 and SAS 9.4. Participants were asked about intake frequencies of SSB and were grouped into four different SSB intake groups based on the combination of high or low frequency (including moderate frequency) of intake of sweetened tea and soda/sports/energy drinks. Results indicated over 99 % of teens reported having at least one SSB in the past week. Smoking status was significantly associated with SSB intake types with high tea intake (high tea and low soda (HL) group, OR 7·56, P < 0·001; high tea and high soda (HH) group, OR 9·96, P < 0·001). After adjustment for potential confounders, adolescents in the low tea and high soda (LH) group (ß = 0·05, P = 0·034) had significantly higher mean serum uric acid values. In conclusion, sugary tea remains the SSB of choice for Taiwanese adolescents. Those with a frequent intake of soda/sports/energy drinks had a higher chance of being hyperuricaemic.

Lower Extremity Stiffness Predicts Ground Reaction Force Loading Rate in Heel Strike Runners.

PURPOSE: High vertical ground reaction force (vGRF) loading rates are thought to contribute to lower extremity injuries in runners. Given that elevated lower extremity stiffness has been reported to be associated with increased GRFs, the purpose of the current study was to determine if overall lower extremity stiffness, individual joint angular excursions and/or torsional stiffness are predictive of the average vGRF loading rate during running. METHODS: Forty heel strike runners (20 men and 20 women) ran overground at a speed of 3.4 m·s. Average vGRF loading rate, lower extremity stiffness, and hip, knee, and ankle joint excursions and torsional stiffness from initial contact to the first peak of the vGRF were quantified. Stepwise multiple linear regression was performed to determine the best predictor(s) of average vGRF loading rate. RESULTS: Lower extremity stiffness was found to the best predictor of average vGRF loading rate (R = 0.68, P < 0.001). The second variable that entered the stepwise regression model of average vGRF loading rate was knee joint excursion (ΔR = 0.03, P = 0.023). CONCLUSIONS: Increased lower extremity stiffness immediately after initial contact may expose heel strike runners to higher vGRF loading rates.

Pre-existing Symptoms and Healthcare Utilization Prior to Diagnosis of Neuroendocrine Tumors: A SEER-Medicare Database Study.

The incidence and prevalence of neuroendocrine tumors (NETs) are continually increasing. While it is known that NET symptoms often predate diagnosis, their prevalence and impact on resource utilization and costs are largely unknown. We identified 9,319 elderly patients diagnosed with NETs between 1/2003 and 12/2011 from the Surveillance, Epidemiology and End Results (SEER)-Medicare. We examined the patients' conditions potentially associated with NET, resource utilization and costs during the year before diagnosis. We found that NET patients were more likely to have diagnoses of hypertension (63.8% vs. 53.3%), abdominal pain (22.2% vs. 7.6%), heart failure (11.7% vs. 8.0%), diarrhea (5.8% vs. 1.8%), peripheral edema (5.4% vs. 3.8%) and irritable bowel syndrome (1.2% vs. 0.5%) compared to the non-cancer control group. They also had much higher resource utilization including number of outpatient visits (mean: 22.1 vs. 17.2), percentage with ER visits (20.9% vs. 11.6%), and hospitalizations (28.4% vs. 17.0%). Similarly, NET patients incurred significantly higher total (mean: $14602 vs. $9464), outpatient (mean: $5987 vs. $4253), and inpatient costs (mean: $8615 vs. $5211). This first population-based study on the pre-diagnosis symptoms and healthcare utilization found that NET patients were more likely to have certain conditions and incur higher resource utilizations and costs.

Combination of arginine, glutamine, and omega-3 fatty acid supplements for perioperative enteral nutrition in surgical patients with gastric adenocarcinoma or gastrointestinal stromal tumor (GIST): A prospective, randomized, double-blind study.

Background: Perioperative enteral nutrition (EN) enriched with immune-modulating substrates is preferable for patients undergoing major abdominal cancer surgery. In this study, perioperative EN enriched with immune-modulating nutrients such as arginine, glutamine, and omega-3 fatty acids was evaluated for its anti-inflammatory efficacy in patients with gastric adenocarcinoma or gastrointestinal stromal tumor (GIST) receiving curative surgery. Materials and Methods: This prospective, randomized, double-blind study recruited 34 patients with gastric adenocarcinoma or gastric GIST undergoing elective curative surgery. These patients were randomly assigned to the study group, receiving immune-modulating nutrient-enriched EN, or the control group, receiving standard EN from 3 days before surgery (preoperative day 3) to up to postoperative day 14 or discharge. Laboratory and inflammatory parameters were assessed on preoperative day 3 and postoperative day 14 or at discharge. Adverse events (AEs) and clinical outcomes were documented daily and compared between groups. Results: No significant differences were observed between the two groups in selected laboratory and inflammatory parameters, or in their net change, before and after treatment. AEs and clinical outcomes, including infectious complications, overall complications, time to first bowel action, and length of hospital stay after surgery, were comparable between treatment groups (all P > 0.05). Conclusion: Immune-modulating nutrient-enriched EN had no prominent immunomodulation effect compared with that of standard EN.

Clinical, pathological, and demographic factors associated with development of recurrences after surgical resection in elderly patients with neuroendocrine tumors.

BACKGROUND: Incidence of locoregional neuroendocrine tumors (NETs) is rising. However, after curative resection, the patterns and risk factors associated with recurrence remain unknown. Consensus guidelines recommend surveillance every 6-12 months for up to 10 years after surgery for resected, well-differentiated NETs irrespective of patient demographics, site, grade or stage of tumor with few exceptions. PATIENTS AND METHODS: From the Surveillance, Epidemiology, and End Results (SEER)-Medicare database, we identified localized and regional stage NET patients who underwent surgical resection between January 2002 and December 2011. Development of recurrence was identified by capturing at least two claims indicative of metastatic disease until 31 December 2013. RESULTS: Of the 2366 identified patients (median age 73 years), 369 (16%) developed metastatic disease within 5 years and only an additional 1% developed metastases between years 5 and 10 with the majority dying due to unrelated causes. The 5-year risk of developing metastases (hazard ratio, HR) varied significantly (log-rank P < 0.001) by grade: 9.9% versus 25.9% (2.2) versus 48.1% (4.4) for grades 1, 2, and ≥ 3, respectively; stage: 10.3% versus 31.1% (2.8) for localized versus regional; primary tumor size: 7.6% versus 15% (1.3) versus 26.6% (1.5) for <1, 1-2, and > 2 cm, respectively; and site: ranging from 11.3% for colon to 23.9% for pancreas. CONCLUSIONS: Contrary to current guidelines, our study suggests that surveillance recommendations should be tailored according to patient and tumor characteristics. Surveillance past 5 years may be avoided in elderly patients with competing morbidities or low risk of recurrence. Pancreatic, lung, higher grade, and regional NETs have a higher risk of recurrence and may be considered for future adjuvant trials.

Hippocampal Atrophy Is Associated with Altered Hippocampus-Posterior Cingulate Cortex Connectivity in Mesial Temporal Lobe Epilepsy with Hippocampal Sclerosis.

BACKGROUND AND PURPOSE: Unilateral mesial temporal lobe epilepsy and hippocampal sclerosis have structural and functional abnormalities in the mesial temporal regions. To gain insight into the pathophysiology of the epileptic network in mesial temporal lobe epilepsy with hippocampal sclerosis, we aimed to clarify the relationships between hippocampal atrophy and the altered connection between the hippocampus and the posterior cingulate cortex in patients with mesial temporal lobe epilepsy with hippocampal sclerosis. MATERIALS AND METHODS: Fifteen patients with left mesial temporal lobe epilepsy with hippocampal sclerosis and 15 healthy controls were included in the study. Multicontrast MR imaging, including high-resolution T1WI, diffusion spectrum imaging, and resting-state fMRI, was performed to measure the hippocampal volume, structural connectivity of the inferior cingulum bundle, and intrinsic functional connectivity between the hippocampus and the posterior cingulate cortex, respectively. RESULTS: Compared with controls, patients had decreased left hippocampal volume (volume ratio of the hippocampus and controls, 0.366% ± 0.029%; patients, 0.277% ± 0.063%, corrected P = .002), structural connectivity of the bilateral inferior cingulum bundle (generalized fractional anisotropy, left: controls, 0.234 ± 0.020; patients, 0.193 ± 0.022, corrected P = .0001, right: controls, 0.226 ± 0.022; patients, 0.208 ± 0.017, corrected P = .047), and intrinsic functional connectivity between the left hippocampus and the left posterior cingulate cortex (averaged z-value: controls, 0.314 ± 0.152; patients, 0.166 ± 0.062). The left hippocampal volume correlated with structural connectivity positively (standardized ß = 0.864, P = .001), but it had little correlation with intrinsic functional connectivity (standardized ß = -0.329, P = .113). On the contralesional side, the hippocampal volume did not show any significant correlation with structural connectivity or intrinsic functional connectivity (F2,12 = 0.284, P = .757, R2 = 0.045). CONCLUSIONS: In left mesial temporal lobe epilepsy with hippocampal sclerosis, the left inferior cingulum bundle undergoes degeneration in tandem with the left hippocampal volume, whereas intrinsic functional connectivity seems to react by compensating the loss of connectivity. Such insight might be helpful in understanding the development of the epileptic network in left mesial temporal lobe epilepsy with hippocampal sclerosis.

Hypertension impairs hippocampus-related adult neurogenesis, CA1 neuron dendritic arborization and long-term memory.

Hypertension is associated with neurodegenerative diseases and cognitive impairment. Several studies using spontaneous hypertensive rats to study the effect of hypertension on memory performance and adult hippocampal neurogenesis have reached inconsistent conclusions. The contradictory findings may be related to the genetic variability of spontaneous hypertensive rats due to the conventional breeding practices. The objective of this study is to examine the effect of hypertension on hippocampal structure and function in isogenic mice. Hypertension was induced by the '2 kidneys, 1 clip' method (2K1C) which constricted one of the two renal arteries. The blood pressures of 2K1C mice were higher than the sham group on post-operation day 7 and remained high up to day 28. Mice with 2K1C-induced hypertension had impaired long-term, but not short-term, memory. Dendritic complexity of CA1 neurons and hippocampal neurogenesis were reduced by 2K1C-induced hypertension on post-operation day 28. Furthermore, 2K1C decreased the levels of hippocampal brain-derived neurotrophic factor, while blood vessel density and activation status of astrocytes and microglia were not affected. In conclusion, hypertension impairs hippocampus-associated long-term memory, dendritic arborization and neurogenesis, which may be caused by down-regulation of brain-derived neurotrophic factor signaling pathways.

Has racial difference in cause-specific death improved in older patients with late-stage breast cancer?

BACKGROUND: Research on temporal mortality trends for stage IV breast cancer is limited, especially among older patients by race. We evaluated factors associated with overall, breast cancer-specific and other-cause mortalities using contemporary population data. PATIENTS AND METHODS: Using the Surveillance, Epidemiology, and End Results-Medicare linked data, we identified older women (≥ 66 years) with stage IV breast cancer diagnosed in 2002-2009. Overall mortality was estimated by the Kaplan-Meier method, compared by log-rank tests, and modeled by Cox models. Competing risk analysis was used to evaluate breast cancer-specific and other-cause mortalities. RESULTS: The median overall survival time for non-Hispanic blacks improved from 8.6 months in 2002-2003 to 9.9 months in 2007-2009, whereas that for non-Hispanic whites improved from 12.1 to 14.8 months. In the multivariate model, the risk of breast cancer-specific death for patients diagnosed in 2007-2009 was significantly lower (P = 0.02), whereas the risk of other-cause mortality changed little (P = 0.88) compared with those risks for patients diagnosed in 2002-2003. Non-Hispanic blacks had the higher risk of both mortality types compared with non-Hispanic whites; a diagnosis time-race interaction term was not statistically significant for either cause of death. CONCLUSION: Breast cancer-specific mortality among older women modestly improved from 2002 to 2009 across all races, but not other-cause mortality. Racial disparity in mortality persisted, but did not widen in this period. Efforts should be devoted to improving other-cause mortality for all women, with special attention toward decreasing breast cancer mortality for non-Hispanic black women.

Innovation of a syringe needle auto-detaching device for clinicians.

BACKGROUND: Needle-stick injuries accounts for a great proportion of all medical accidents in developing and undeveloped countries. The main cause of needle-stick accident injuries is the medical personnel's ``recovering'' the needle action after injection. OBJECTIVE: This study applies an electronic technique to the needling instrument for the purpose of automatically detaching the needle. The proposed method can effectively avoid needle-stick accident injury when ``recovering'' the needle. METHODS: The syringe needle auto-detaching device includes an abutment on which there is a turntable mechanism composed of a pedestal, a turn-table and a driving unit. A photo interrupter on the pedestal detects the rotational angle of the turntable and controls the stepping motor through a control circuit. An optical sensor is located on the upper end of the sensing mechanism. When the syringe is inserted into the syringe plughole the exposed portion of the needle will be detected by the optical sensor. After the syringe is placed into the plughole, its needle will be detected by the sensor. At this time the needle will be detached from the syringe and automatically fall down into the needle collection box. RESULTS: The syringe needle auto-detaching device was fatigue tested for an extensive period of time (A group: 1000 times/day for 3 ml, B group: 1000 times/day for 5 ml, C group: 1000 times/day for 3 ml and 5 ml staggered, D group: 1000 times/day for 3 ml and 5 ml randomized). The needle and syringe detachment rates were 100% in all test groups. CONCLUSIONS: The syringe needle auto-detaching device developed in this study, in that the clinician performs only one step to dispose a needle. Six syringe needle sets can be managed sequence second by second. The proposed device without all of the risk factors of the traditional syringe needle detachment device.

Immunologic assessment and KMT2D mutation detection in Kabuki syndrome.

Kabuki or Niikawa-Kuroki syndrome (KS) is a rare disorder with multiple malformations and recurrent infections, especially otitis media. This study aimed to investigate the genetic defects in Kabuki syndrome and determine if immune status is related to recurrent otitis media. Fourteen patients from 12 unrelated families were enrolled in the 9-year study period (2005-2013). All had Kabuki faces, cleft palate, developmental delay, mental retardation, and the short fifth finger. Recurrent otitis media (12/14) and hearing impairment (8/14) were also more common features. Immunologic analysis revealed lower memory CD19+ cells (11/13), lower memory CD4+ cells (8/13), undetectable anti-HBs antibodies (7/13), and antibody deficiency (7/13), including lower IgA (4), IgG (2), and IgG2 (1). Naïve emigrant lymphocytes, lymphocyte proliferation function, complement activity, and superoxide production in polymorphonuclear cells were all normal. All the patients had KMT2D mutations and 10 novel mutations of R1252X, R1757X,Y1998C, P2550R fs2604X, Q4013X, G5379X, E5425K, R5432X, R5432W, and R5500W. Resembling the phenotype of common variable immunodeficiency, KS patients with antibody deficiency, decreased memory cells, and poor vaccine response increased susceptibility to recurrent otitis media. Large-scale prospective studies are warranted to determine if regular immunoglobulin supplementation decreases the frequency of otitis media and severity of hearing impairment.

Cost-effectiveness of alternative strategies for integrating MRI into breast cancer screening for women at high risk.

BACKGROUND: Magnetic resonance imaging (MRI) is recommended for women at high risk for breast cancer. We evaluated the cost-effectiveness of alternative screening strategies involving MRI. METHODS: Using a microsimulation model, we generated life histories under different risk profiles, and assessed the impact of screening on quality-adjusted life-years, and lifetime costs, both discounted at 3%. We compared 12 screening strategies combining annual or biennial MRI with mammography and clinical breast examination (CBE) in intervals of 0.5, 1, or 2 years vs without, and reported incremental cost-effectiveness ratios (ICERs). RESULTS: Based on an ICER threshold of $100,000/QALY, the most cost-effective strategy for women at 25% lifetime risk was to stagger MRI and mammography plus CBE every year from age 30 to 74, yielding ICER $58,400 (compared to biennial MRI alone). At 50% lifetime risk and with 70% reduction in MRI cost, the recommended strategy was to stagger MRI and mammography plus CBE every 6 months (ICER=$84,400). At 75% lifetime risk, the recommended strategy is biennial MRI combined with mammography plus CBE every 6 months (ICER=$62,800). CONCLUSIONS: The high costs of MRI and its lower specificity are limiting factors for annual screening schedule of MRI, except for women at sufficiently high risk.

Impaired neural drive in patients with low back pain.

BACKGROUND: Control of trunk movement relies on the integration between central neuronal circuits and peripheral skeletomuscular activities and it can be altered by pain. There is increasing evidence that there are deficits within the central nervous system controlling the trunk muscles in people with low back pain (LBP). However, it is unclear how LBP impacts upon neural drive to back muscles at different levels of voluntary contraction. Therefore, the purpose of this study was to investigate if neural drive is impaired in these patients. METHODS: Seventeen patients with LBP and 11 healthy controls were recruited. Bilateral electromyographic (EMG) recordings were obtained from the erector spinae (ES) muscles at two vertebral levels (T12 and L4). Participants performed a series of brief isometric back extensions (50-100% maximum voluntary contraction - MVC), during which transcranial magnetic stimulation was delivered. The size of the evoked (superimposed) twitch was measured using dynamometry. RESULTS: The size of the superimposed twitch decreased linearly with increasing contraction strength in the controls; however, this linear relationship was not observed in the patients. Additionally, patients had larger superimposed twitches and longer time-to-peak amplitudes during MVCs than those observed in controls. Furthermore, patients had lower MVC and root-mean-square EMG activity of ES muscles during MVCs. CONCLUSIONS: A decline of central neural drive to the back muscles at high level of voluntary contraction was observed in patients with LBP. These results suggest that it might be pertinent to include neuromuscular facilitation programmes and therapeutic exercise utilizing high voluntary contractions for patients with LBP.

Hepatocellular carcinoma with colonic metastasis.

Hepatocellular carcinoma with colonic metastasis is rare. It mainly occurs by direct invasion and presents with bloody stools. We describe a patient with haematogenous metastasis to the rectum who presented with tenesmus. To our knowledge, such an association has not been reported previously. Colonic metastasis should be considered when patients with hepatocellular carcinoma present with bloody stools or tenesmus.

Low-cost computer mouse for the elderly or disabled in Taiwan.

BACKGROUND: A mouse is an important communication interface between a human and a computer, but it is still difficult to use for the elderly or disabled. OBJECTIVE: To develop a low-cost computer mouse auxiliary tool. METHODS: The principal structure of the low-cost mouse auxiliary tool is the IR (infrared ray) array module and the Wii icon sensor module, which combine with reflective tape and the SQL Server database. RESULTS: This has several benefits including cheap hardware cost, fluent control, prompt response, adaptive adjustment and portability. Also, it carries the game module with the function of training and evaluation; to the trainee, it is really helpful to upgrade the sensitivity of consciousness/sense and the centralization of attention. The intervention phase/maintenance phase, with regard to clicking accuracy and use of time, p value (p< 0.05) reach the level of significance. CONCLUSIONS: The development of the low cost adaptive computer mouse auxiliary tool was completed during the study and was also verified as having the characteristics of low cost, easy operation and the adaptability. To patients with physical disabilities, if they have independent control action parts of their limbs, the mouse auxiliary tool is suitable for them to use, i.e. the user only needs to paste the reflective tape by the independent control action parts of the body to operate the mouse auxiliary tool.