Gene-set integrative analysis of multi-omics data using tensor-based association test.

MOTIVATION: Facilitated by technological advances and the decrease in costs, it is feasible to gather subject data from several omics platforms. Each platform assesses different molecular events, and the challenge lies in efficiently analyzing these data to discover novel disease genes or mechanisms. A common strategy is to regress the outcomes on all omics variables in a gene set. However, this approach suffers from problems associated with high-dimensional inference. RESULTS: We introduce a tensor-based framework for variable-wise inference in multi-omics analysis. By accounting for the matrix structure of an individual's multi-omics data, the proposed tensor methods incorporate the relationship among omics effects, reduce the number of parameters, and boost the modeling efficiency. We derive the variable-specific tensor test and enhance computational efficiency of tensor modeling. Using simulations and data applications on the Cancer Cell Line Encyclopedia (CCLE), we demonstrate our method performs favorably over baseline methods and will be useful for gaining biological insights in multi-omics analysis. AVAILABILITY AND IMPLEMENTATION: R function and instruction are available from the authors' website: https://www4.stat.ncsu.edu/~jytzeng/Software/TR.omics/TRinstruction.pdf. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Trophic Dynamics and Feeding Ecology of Skipjack Tuna (Katsuwonus pelamis) off Eastern and Western Taiwan.

The skipjack tuna (Katsuwonus pelamis) is a mesopredator fish species with seasonal abundance in waters off Taiwan. Regional ecological and life-history information has been historically lacking for this species. In recent years, stable isotope analysis (SIA) of carbon and nitrogen has been used to assess predator feeding ecology and broader ecosystem trophic dynamics. This study evaluated comparative skipjack feeding ecology in distinct regions off Taiwan, combining traditional stomach content analysis with SIA of individuals off western (n = 43; 2020) and eastern (n = 347; 2012-2014 and n = 167; 2020) Taiwan. The stomach content analysis showed the most important prey to be ponyfish (Photopectoralis bindus) in western Taiwan and epipelagic squids (Myopsina spp.) and carangids (Decapterus macrosoma;) in eastern Taiwan from 2012 to 2014 and epipelagic carangids (Decapterus spp.) and flying fishes (Cheilopogon spp.) in eastern Taiwan in 2020, suggesting that the skipjack tuna is a generalist predator across regions. In contrast, time-integrated diet estimates from Bayesian mixing models indicated the importance of cephalopods and crustaceans as prey, potentially demonstrating more mesopelagic feeding in less productive waters during skipjack migrations outside the study regions. Skipjack off western Taiwan had a slightly higher estimated trophic position than in the waters off eastern Taiwan, potentially driven by the varying nutrient-driven pelagic food web structures. Skipjack SI values increased with body size off eastern Taiwan but not in western waters, suggesting that opportunistic predation can still result in different predator-prey size dynamics between regions.

Robust Aggregation for Federated Learning by Minimum γ-Divergence Estimation.

Federated learning is a framework for multiple devices or institutions, called local clients, to collaboratively train a global model without sharing their data. For federated learning with a central server, an aggregation algorithm integrates model information sent from local clients to update the parameters for a global model. Sample mean is the simplest and most commonly used aggregation method. However, it is not robust for data with outliers or under the Byzantine problem, where Byzantine clients send malicious messages to interfere with the learning process. Some robust aggregation methods were introduced in literature including marginal median, geometric median and trimmed-mean. In this article, we propose an alternative robust aggregation method, named γ-mean, which is the minimum divergence estimation based on a robust density power divergence. This γ-mean aggregation mitigates the influence of Byzantine clients by assigning fewer weights. This weighting scheme is data-driven and controlled by the γ value. Robustness from the viewpoint of the influence function is discussed and some numerical results are presented.

Risk of chronic kidney disease in patients with kidney stones-a nationwide cohort study.

BACKGROUND: Chronic kidney disease (CKD) and kidney stones are common in Taiwan; in particular, CKD has a high prevalence but low self-awareness rate. CKD-related risk factors such as diabetes, hypertension, and nephrotoxic drugs are well-known and uncontested; however, kidney stones are relatively less studied and easily overlooked as a risk factor. The objective of this study was to investigate whether kidney stones are a risk factor for CKD. METHODS: We conducted a nationwide population-based matched cohort study to assess the risk of incident CKD in people with kidney stones. Data on incident stones formers in the year 2001-excluding those with a history of CKD-were obtained from Taiwan's National Health Insurance database. Stone formers were matched (1:4) to control subjects according to sex, age, and index date. The total observation period of the study was 10 years, and the primary end-point was the occurrence of CKD. Student's t-test and Chi-squared test were used to compare continuous and categorical data, respectively. Logistic regression was used to calculate the odds ratio of kidney stone patients with incident CKD relative to the control group. Cox proportional hazard regression model was used to obtain the hazard ratio for development of incident CKD among patients with kidney stones. RESULTS: The incidence of CKD in the kidney stone cohort was 11.2%, which was significantly higher than that of the control group (P < .001). Survival analysis showed that the stones cohort was 1.82 times more likely to experience CKD than the controls. Age, sex, hypertension, diabetes mellitus, and hyperlipidemia increased the risk of CKD incidence (1.04, 1.27, 1.55, 3.31, and 1.25 times, respectively). CONCLUSION: Kidney stones are a definite risk factor for CKD; therefore, patients with stones are suggested to undergo regular renal function monitoring and receive appropriate treatment to avoid CKD.

A direct connection promotes time efficiency for transfer of ST-elevation myocardial infarction patients.

INTRODUCTION: Reducing the delay in time to primary percutaneous coronary intervention (PCI) for acute coronary syndrome patients in the non-urban emergency department (ED) is of critical importance. Conventionally, physicians in a non-PCI-capable, non-urban local emergency department (LED) require approval from a tertiary university hospital emergency department (TUH-ED) prior to transferring eligible STEMI patients for PCI procedures. To reduce the ED delay time, this study developed a direct connection between the LED and the cardiac catheterisation laboratory in the TUH (TUH cath lab). METHODS: ST-elevation myocardial infarction (STEMI) patients' medical records for 2014 to 2017, from a non-PCI regional hospital located in one of the rural counties in central Taiwan and a TUH-ED in a metropolitan area in the centre of Taiwan, were retrospectively collected and classified into two categories: the LED referral (group A) and the TUH-non-referral (group B). This study compared the ED delay time between TUH non-referral patients in the TUH and LED referral patients in the LED, to determine whether a direct connection reduces current LED delay time. RESULTS: A total of 214 patients (group A, n=62; group B, n=152) who underwent PCI procedures at the TUH were enrolled in the study. ED delay times in the LED were significantly less than the TUH-ED (45.0 v 66.0 min, p<0.01.) Conclusion: The direct connection between the LED and the TUH cath lab effectively shortened the ED delay time in the LED, allowing for earlier primary PCI procedures for the transferred STEMI patients.

A robust removing unwanted variation-testing procedure via γ -divergence.

Identification of differentially expressed genes (DE genes) is commonly conducted in modern biomedical research. However, unwanted variation inevitably arises during the data collection process, which can make the detection results heavily biased. Various methods have been suggested for removing the unwanted variation while keeping the biological variation to ensure a reliable analysis result. Removing unwanted variation (RUV) has recently been proposed for this purpose, which works by virtue of negative control genes. On the other hand, outliers frequently appear in modern high-throughput genetic data, which can heavily affect the performances of RUV and its downstream analysis. In this work, we propose a robust RUV-testing procedure (a robust RUV procedure to remove unwanted variance, followed by a robust testing procedure to identify DE genes) via γ -divergence. The advantages of our method are twofold: (a) it does not involve any modeling for the outlier distribution, which makes it applicable to various situations; (b) it is easy to implement in the sense that its robustness is controlled by a single tuning parameter γ of γ -divergence, and a data-driven criterion is developed to select γ . When applied to real data sets, our method can successfully remove unwanted variation, and was able to identify more DE genes than conventional methods.

Sufficient dimension reduction via random-partitions for the large-p-small-n problem.

Sufficient dimension reduction (SDR) continues to be an active field of research. When estimating the central subspace (CS), inverse regression based SDR methods involve solving a generalized eigenvalue problem, which can be problematic under the large-p-small-n situation. In recent years, new techniques have emerged in numerical linear algebra, called randomized algorithms or random sketching, for high-dimensional and large scale problems. To overcome the large-p-small-n SDR problem, we combine the idea of statistical inference with random sketching to propose a new SDR method, called integrated random-partition SDR (iRP-SDR). Our method consists of the following three steps: (i) Randomly partition the covariates into subsets to construct an envelope subspace with low dimension. (ii) Obtain a sketch of the CS by applying a conventional SDR method within the constructed envelope subspace. (iii) Repeat the above two steps many times and integrate these multiple sketches to form the final estimate of the CS. After describing the details of these steps, the asymptotic properties of iRP-SDR are established. Unlike existing methods, iRP-SDR does not involve the determination of the structural dimension until the last stage, which makes it more adaptive to a high-dimensional setting. The advantageous performance of iRP-SDR is demonstrated via simulation studies and a practical example analyzing EEG data.

Endoscopic transorbital approach to anterolateral skull base through inferior orbital fissure: a cadaveric study.

BACKGROUND: Endoscopic transorbital approach (eTOA) has been announced as an alternative minimally invasive surgery to skull base. Owing to the inferior orbital fissure (IOF) connecting the orbit with surrounding pterygopalatine fossa (PPF), infratemporal fossa (ITF), and temporal fossa, the idea of eTOA to anterolateral skull base through IOF is postulated. The aim of this study is to access its practical feasibility. METHODS: Anatomical dissections were performed in five human cadaveric heads (10 sides) using 0-degree and 30-degree endoscopes. A stepwise description of eTOA to anterolateral skull base through IOF was documented. The anterosuperior corner of the maxillary sinus in the horizontal plane of the upper edge of zygomatic arch was defined as reference point (RP). The distances between the RP to the foramen rotundum (FR), foramen ovale (FO), and Gasserian ganglion (GG) were measured. The exposed area of anterolateral skull base in the coronal plane of the posterior wall of the maxillary sinus was quantified. RESULTS: The surgical procedure consisted of six steps: (1) lateral canthotomy with cantholysis and preseptal lower eyelid approach with periorbita dissection; (2) drilling of the ocular surface of greater sphenoid wing and lateral orbital rim osteotomy; (3) entry into the maxillary sinus and exposure of PPF and ITF; (4) mobilization of infraorbital nerve with drilling of the infratemporal surface of the greater sphenoid wing and pterygoid process; (5) exposure of middle cranial fossa, Meckel's cave, and lateral wall of cavernous sinus; and (6) reconstruction of orbital floor and lateral orbital rim. The distances measured were as follows: RP-FR = 45.0 ± 1.9 mm, RP-FO = 55.7 ± 0.5 mm, and RP-GG = 61.0 ± 1.6 mm. In comparison with the horizontal portion of greater sphenoid wing, the superior and inferior axes of the exposed area were 22.3 ± 2.1 mm and 20.5 ± 1.8 mm, respectively. With reference to the FR, the medial and lateral axes of the exposed area were 11.6 ± 1.1 mm and 15.8 ± 1.6 mm, respectively. CONCLUSIONS: The eTOA through IOF can be used as a minimally invasive surgery to access whole anterolateral skull base. It provides a possible resolution to target lesion involving multiple compartments of anterolateral skull base.

Endoscopic transorbital transtentorial approach to middle incisural space: preclinical cadaveric study.

BACKGROUND: Endoscopic transorbital approach is a novel development of minimally invasive skull base surgery. Recently, anatomical studies have started to discuss the expanded utilization of endoscopic transorbital route for intracranial intradural lesions. The goal of this cadaveric study is to assess the feasibility of endoscopic transorbital transtentorial approach for exposure of middle incisural space. METHODS: Anatomical dissections were performed in four human cadaveric heads (8 sides) using 0- and 30-degree endoscopes. A stepwise description of endoscopic transorbital transtentorial approach to middle incisural space and related anatomy was provided. RESULTS: Orbital manipulation following superior eyelid crease incision with lateral canthotomy and cantholysis established space for bone drilling. Extradural stage consisted of extensive drilling of orbital roof of frontal bone, lessor, and greater wings of sphenoid bone. Intradural stage was composed of dissection of sphenoidal compartment of Sylvian fissure, lateral mobilization of mesial temporal lobe, and penetration of tentorium. A cross-shaped incision of tentorium provided direct visualization of crural cistern with anterolateral aspect of cerebral peduncle and upper pons. Interpeduncular cistern, prepontine cistern, and anterior portions of ambient and cerebellopontine cisterns were exposed by 30-degree endoscope. CONCLUSION: The endoscopic transorbital transtentorial approach can be used as a minimally invasive surgery for exposure of middle incisural space. Extensive drilling of sphenoid wing and lateral mobilization of mesial temporal lobe are the main determinants of successful dissection. Further studies are needed to confirm the clinical feasibility of this novel approach.

Stable isotope analysis reveals ontogenetic feeding shifts in Pacific blue marlin (Makaira nigricans) off eastern Taiwan.

To gain a better understanding of the trophic ecology of Pacific blue marlin Makaira nigricans off eastern Taiwan, nitrogen and carbon stable isotopes (δ15 N and δ13 C) and Bayesian mixing models were used to explore trophic dynamics and potential ontogenetic feeding shifts across M. nigricans of different size classes. Makaira nigricans samples from east of Taiwan (n = 213) and Palau (n = 37), as well as their prey (n = 70), were collected during 2012 and 2013. Results indicated increases in δ15 N with size, with values of larger size classes (> 200 cm eye-to-fork length; LEF ) significantly higher than those < 200 cm LEF . Values of δ13 C were negatively correlated with size. Makaira nigricans > 200 cm LEF had the highest estimated trophic position (4.44) and also exhibited ontogenetic changes in trophic position. Large M. nigricans fed more on dolphinfish Coryphaena hippurus and hairtail Trichiurus lepturus, while smaller M. nigricans consumed smaller forage fish (e.g., moonfish Mene maculata) and cephalopods. These changes may relate to greater swimming speeds and vertical habitat use in larger M. nigricans, allowing capture and consumption of larger prey items at higher trophic positions. The high trophic level of M. nigricans east of Taiwan confirms its important role as an apex predator in marine food webs and how ecological role changes with size.

Robust mislabel logistic regression without modeling mislabel probabilities.

Logistic regression is among the most widely used statistical methods for linear discriminant analysis. In many applications, we only observe possibly mislabeled responses. Fitting a conventional logistic regression can then lead to biased estimation. One common resolution is to fit a mislabel logistic regression model, which takes into consideration of mislabeled responses. Another common method is to adopt a robust M-estimation by down-weighting suspected instances. In this work, we propose a new robust mislabel logistic regression based on γ-divergence. Our proposal possesses two advantageous features: (1) It does not need to model the mislabel probabilities. (2) The minimum γ-divergence estimation leads to a weighted estimating equation without the need to include any bias correction term, that is, it is automatically bias-corrected. These features make the proposed γ-logistic regression more robust in model fitting and more intuitive for model interpretation through a simple weighting scheme. Our method is also easy to implement, and two types of algorithms are included. Simulation studies and the Pima data application are presented to demonstrate the performance of γ-logistic regression.

Using proton pump inhibitors correlates with an increased risk of chronic kidney disease: a nationwide database-derived case-controlled study.

Background: Those taking proton pump inhibitors (PPIs) might have a higher risk of acute kidney injury. The long-term safety, especially the PPI-associated chronic kidney disease (CKD) is the subsequent concern. Objective: This study explores the potential relationship between using PPIs and CKD in Taiwan. Methods: Using a database collated by the Taiwan National Health Insurance programme, we conducted a population-based case-controlled study to identify 16 704 cases of patients aged 20 years or older with newly diagnosed CKD between 2000 and 2013. 16 704 controls were randomly selected and were matched by sex, age and comorbidities. 'Use' of PPIs was defined as when subjects had received at least a prescription for PPIs before the index date. 'Non-use' was defined as subjects who had never received a prescription for PPIs before the index date. The odds ratio (OR) for CKD associated with the use of PPIs was estimated by a logistic regression model. Results: The OR for CKD was 1.41 for subjects using PPIs [95% confidence interval (CI) 1.34, 1.48] compared with subjects who had never used PPIs. Almost all major types of PPIs present a weak association with increased odds of CKD in cumulative duration and dosage regression analysis. The OR in relation to cumulative duration (per month) of PPIs use was 1.02 (95% CI 1.01, 1.02) and the OR in relation to cumulative dosage (per microgram) of PPIs use was 1.23 (95% CI 1.18, 1.28). Conclusions: Using PPIs presented 1.4-fold higher odds of CKD in Taiwan health insurance claims data analysis.

Activated Integrated Stress Response Induced by Salubrinal Promotes Cisplatin Resistance in Human Gastric Cancer Cells via Enhanced xCT Expression and Glutathione Biosynthesis.

The integrated stress response (ISR) pathway is essential for adaption of various stresses and is related to mitochondrion-to-nucleus communication. Mitochondrial dysfunction-induced reactive oxygen species (ROS) was demonstrated to activate general control nonderepressible 2 (GCN2)⁻eukaryotic translation initiation factor 2α (eIF2α)⁻activating transcription factor-4 (ATF4) pathway-mediated cisplatin resistance of human gastric cancer cells. However, whether or how ISR activation per se could enhance chemoresistance remains unclear. In this study, we used eIF2α phosphatase inhibitor salubrinal to activate the ISR pathway and found that salubrinal reduced susceptibility to cisplatin. Moreover, salubrinal up-regulated ATF4-modulated gene expression, and knockdown of ATF4 attenuated salubrinal-induced drug resistance, suggesting that ATF4-modulated genes contribute to the process. The ATF4-modulated genes, xCT (a cystine/glutamate anti-transporter), tribbles-related protein 3 (TRB3), heme oxygenase 1 (HO-1), and phosphoenolpyruvate carboxykinase 2 (PCK2), were associated with a poorer prognosis for gastric cancer patients. By silencing individual genes, we found that xCT, but not TRB3, HO-1, or PCK2, is responsible for salubrinal-induced cisplatin resistance. In addition, salubrinal increased intracellular glutathione (GSH) and decreased cisplatin-induced lipid peroxidation. Salubrinal-induced cisplatin resistance was attenuated by inhibition of xCT and GSH biosynthesis. In conclusion, our results suggest that ISR activation by salubrinal up-regulates ATF4-modulated gene expression, increases GSH synthesis, and decreases cisplatin-induced oxidative damage, which contribute to cisplatin resistance in gastric cancer cells.

Sufficient dimension reduction with additional information.

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Assessment of Educational Needs and Quality of Life of Chronic Hepatitis Patients.

BACKGROUND: Patient education is crucial in improving the health-related quality of life (HRQOL) of patients. At the same, understanding the concerns and needs of patients is essential in providing appropriate education. This study assessed the educational needs and HRQOL experienced by chronic hepatitis patients. METHODS: We developed structured questionnaires with satisfactory validity and reliability to assess the educational needs of patients. HROQL was measured using a generic Short Form 36 (SF-36) and a liver disease-specific Chronic Liver Disease Questionnaire (CLDQ). Descriptive statistic measures and Pearson's correlation analysis were applied for data analysis. RESULTS: A total of 135 subjects were recruited from two regional teaching hospitals in Taiwan. "Disease characteristics and management" exhibited the highest mean score (3.17) among all the subscales of educational needs. In comparison with those without antiviral therapy, chronic hepatitis patients undergoing antiviral treatment scored significantly higher on all subscales of educational needs, especially on "side effects of antiviral treatment" (p < 0.010). The median range of the physical component summary score was 45.94, the mental component summary score was 49.37, and the mean CLDQ was 5.70. Several domains of educational needs were significantly inversely correlated with the CLDQ and SF-36 subscales. CONCLUSIONS: Education is highly required by chronic hepatitis patients, especially those receiving antiviral therapy and patients with poor HRQOL. These findings can serve as a useful reference for nursing personnel who perform needs assessment to develop individual nursing instruction and thereby improve the quality of care for chronic hepatitis patients.

Chest compression fraction in ambulance while transporting patients with out-of-hospital cardiac arrest to the hospital in rural Taiwan.

INTRODUCTION: Maintaining the standard two-handed chest compression is difficult in high-speed ambulances in rural areas. METHODS: A retrospective, video-based, observational study was conducted from June to September 2013 in Nantou, a rural county of central Taiwan, to evaluate the chest compression fraction in an ambulance carriage during the travel from the scene to the hospital. The chest compression fraction was calculated as the chest compression time period divided by the ambulance travelling time period; the one-handed and two-handed chest compression fractions were also calculated. RESULTS: During the 4-month study period, a total of 102 videos that were recorded in an ambulance carriage were reviewed, including 97 cases of manual chest compressions. When there was only one emergency medical technician (EMT) in the carriage, the combined chest compression fraction was 50.6±20.7%; when there were two EMTs, the fraction was 58.3±16.0% and the fraction was 58.3±21.0% in a three-EMT scenario (p=0.221). Moreover, in the carriage, EMTs usually performed one-handed chest compressions. CONCLUSIONS: The chest compression fraction was low for patients with out-of-hospital cardiac arrest in a moving ambulance, irrespective of the number of providers. Reasons for this observation, as well as the effectiveness of the one-handed chest compression require further evaluation.

Non-traumatic out-of-hospital cardiac arrest in rural Taiwan: A retrospective study.

OBJECTIVE: Out-of-hospital cardiac arrest (OHCA) studies are usually conducted at metropolitan medical centres. Because rural studies are rare, our study aimed to assess non-traumatic OHCA prevalence and resuscitation outcomes in rural Taiwan. DESIGN: A retrospective observational study. SETTING: All seven designated community hospital emergency departments (ED) in Nantou County, Taiwan. PARTICIPANTS: All OHCA patients from May 2011 to March 2013. MAIN OUTCOME MEASURES: Any return of spontaneous circulation (ROSC) and survival for ED discharge. RESULTS: In the 23-month period, 850 OHCA cases were reported; 741 (87.2%) were non-traumatic. The overall ROSC achievement rate was 19.7%, with 16.4% case survival for ED discharge. Logistic regression identified that arrest in public (OR: 2.62, 95% CI: 1.19-5.78), witness when collapsed (OR: 2.14, 95% CI: 1.28-3.60), and cardiopulmonary resuscitation (CPR) by bystander (OR: 2.09, 95% CI: 1.02-4.26) might increase the likelihood of any ROSC; arrest in public (OR: 2.68, 95% CI: 1.10-6.50), witnessed collapse (OR: 2.26, 95% CI: 1.24-4.09) and CPR by bystander (OR: 2.79, 95% CI: 1.28-6.05) might also increase the likelihood of survival. For non-traumatic OHCA patients conveyed to EDs via emergency medical service system (EMS), a shorter response time (OR: 1.09, 95% CI: 1.01-1.18) and travelling time (OR: 1.04, 95% CI: 1.00-1.09) might also increase the chance of survival. CONCLUSION: Compared to previous data from metropolitan areas, ROSC achievement rate was lower in rural Taiwan. Witness presence, response and travelling times affect ROSC achievement in non-traumatic OHCA patients in rural Taiwan.

Development of risk scoring system for stratifying population for hepatocellular carcinoma screening.

UNLABELLED: The age and risk level that warrants hepatocellular carcinoma (HCC) screening remains to be defined. To develop risk scores for stratifying average-risk population for mass HCC screening, we conducted a pooled analysis using data from three cohorts involving 12,377 Taiwanese adults 20-80 years of age. During 191,240.3 person-years of follow-up, 387 HCCs occurred. We derived risk scores from Cox's model in two thirds of participants and used another one third for model validation. Besides assessing discrimination and calibration, we performed decision curve analysis to translate findings into public health policy. A risk score according to age, sex, alanine aminotransferase, previous chronic liver disease, family history of HCC, and cumulative smoking had good discriminatory accuracy in both model derivation and validation sets (c-statistics for 3-, 5-, and 10-year risk prediction: 0.76-0.83). It also performed well across cohorts and diverse subgroups. Decision curve analyses revealed that use of the score in selecting persons for screening improved benefit at threshold probabilities of >2% 10-year risk, compared with current guidelines and a strategy of screening all hepatitis B carriers. Using 10-year risk 2% as a threshold for initiating screening, the screening age ranged from 20 to ≥60 years, depending on the tertile of risk scores and status of hepatitis B/C virus infection. Combining risk-score tertile levels and hepatitis virus status to stratify participants was more sensitive than current guidelines for HCC detection within 10 years (89.4% vs. 76.8%), especially for young-onset HCCs <50 years (79.4% vs. 40.6%), under slightly lower specificity (67.8% vs. 71.8%). CONCLUSION: A simple HCC prediction algorithm was developed using accessible variables combined with hepatitis virus status, which allows selection of asymptomatic persons for priority of HCC screening.

Nabumetone use and risk of acute pancreatitis in a case-control study.

BACKGROUND: It remains unknown whether nabumetone increases or decreases acute pancreatitis risk. To investigate this, we conducted a population-based case-control study using the database from the Taiwan National Health Insurance Program. METHODS: We analysed 5384 cases aged 20-84 years who had their first attack of acute pancreatitis during 1998-2011 and 21,536 controls without acute pancreatitis, and matched them according to sex, age and year in which acute pancreatitis was diagnosed. Never use of nabumetone was defined as subjects who had never received a nabumetone prescription; active use as subjects receiving a minimum of one prescription for nabumetone within 7 days before acute pancreatitis diagnosis and non-active use of nabumetone as subjects who did not receive a prescription for nabumetone within 7 days before but received at least one prescription for nabumetone ≥8 days before. The odds ratio and 95% confidence interval (CI) were estimated to investigate the risk of acute pancreatitis associated with nabumetone use, using the multivariable unconditional logistic regression model. RESULTS: The adjusted odds ratio of acute pancreatitis was 3.69 (95%CI 1.69, 8.05) for subjects with active use of nabumetone compared with those with never use. The odds ratios decreased to 1.0 (95%CI 0.88, 1.12) for subjects with non-active use. CONCLUSIONS: Active use of nabumetone may increase the risk of acute pancreatitis.

Detection of gene-gene interactions using multistage sparse and low-rank regression.

Finding an efficient and computationally feasible approach to deal with the curse of high-dimensionality is a daunting challenge faced by modern biological science. The problem becomes even more severe when the interactions are the research focus. To improve the performance of statistical analyses, we propose a sparse and low-rank (SLR) screening based on the combination of a low-rank interaction model and the Lasso screening. SLR models the interaction effects using a low-rank matrix to achieve parsimonious parametrization. The low-rank model increases the efficiency of statistical inference and, hence, SLR screening is able to more accurately detect gene-gene interactions than conventional methods. Incorporation of SLR screening into the Screen-and-Clean approach (Wasserman and Roeder, 2009; Wu et al., 2010) is also discussed, which suffers less penalty from Boferroni correction, and is able to assign p-values for the identified variables in high-dimensional model. We apply the proposed screening procedure to the Warfarin dosage study and the CoLaus study. The results suggest that the new procedure can identify main and interaction effects that would have been omitted by conventional screening methods.