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Background: The mortality rate of afebrile bacteremia has been reported to be as high as 45%. This investigation focused on the risk factors and predictive performance of scoring systems for the clinical outcomes of afebrile patients with monomicrobial gram-negative bacteria (GNB) in the emergency department (ED)., Methods: We conducted a retrospective analysis of afebrile adult ED patients with monomicrobial GNB bacteremia from January 2012 to December 2021. We dissected the demographics, clinical pictures, and laboratory investigations. We applied five scoring systems and three revised systems to predict the clinical outcomes., Results: There were 600 patients included (358 males and 242 females), with a mean age of 69.6 ± 15.4 years. The overall mortality rate was 50.17%, reaching 68.52% (74/108) in cirrhotic patients. Escherichia coli was the leading pathogen (42.83%). The non-survivors had higher scores of the original MEDS ( p < 0.001), NEWS ( p < 0.001), MEWS ( p < 0.001), qSOFA ( p < 0.001), and REMS ( p = 0.030). In univariate logistic regression analyses, several risk factors had a higher odds ratio (OR) for mortality, including liver cirrhosis (OR 2.541, p < 0.001), malignancy (OR 2.259, p < 0.001), septic shock (OR 2.077, p = 0.002), and male gender (OR 0.535, p < 0.001). The MEDS demonstrated that the best predictive power with the maximum area under the curve (AUC) was measured at 0.773 at the cut-off point of 11. The AUCs of the original NEWS, MEWS, qSOFA, and REMS were 0.663, 0.584, 0.572, and 0.553, respectively. We revised the original MEDS, NEWS, and qSOFA by adding red cell distribution width, albumin, and lactate scores and found a better predictive power of the AUC of 0.797, 0.719, and 0.694 on the revised MEDS ≥11, revised qSOFA ≥ 3, and revised NEWS ≥ 6, respectively., Conclusions: The original MEDS, revised MEDS, revised qSOFA, and revised NEWS were valuable tools for predicting the mortality risk in afebrile patients with monomicrobial GNB bacteremia. We suggested that clinicians should explore patients with the risk factors mentioned above for possible severe infection, even in the absence of fever and initiate hemodynamic support and early adequate antibiotic therapy in patients with higher scores of the original MEDS (≥11), revised MEDS (≥11), revised NEWS (≥6), and revised qSOFA (≥3).

The collection of known genetic etiologies of neurodevelopmental disorders continues to increase, including several syndromes associated with defects in zinc finger protein transcription factors (ZNFs) that vary in clinical severity from mild learning disabilities and developmental delay to refractory seizures and severe autism spectrum disorder. Here we describe a new neurodevelopmental disorder associated with variants in ZBTB47 (also known as ZNF651), which encodes zinc finger and BTB domain-containing protein 47. Exome sequencing (ES) was performed for five unrelated patients with neurodevelopmental disorders. All five patients are heterozygous for a de novo missense variant in ZBTB47, with p.(Glu680Gly) (c.2039A>G) detected in one patient and p.(Glu477Lys) (c.1429G>A) identified in the other four patients. Both variants impact conserved amino acid residues. Bioinformatic analysis of each variant is consistent with pathogenicity. We present five unrelated patients with de novo missense variants in ZBTB47 and a phenotype characterized by developmental delay with intellectual disability, seizures, hypotonia, gait abnormalities, and variable movement abnormalities. We propose that these variants in ZBTB47 are the basis of a new neurodevelopmental disorder., (© 2023 Wiley Periodicals LLC.)

Cryptococcal infection is usually diagnosed in immunocompromised individuals and those with meningeal involvement, accounting for most cryptococcosis. Cryptococcemia indicates a poor prognosis and prolongs the course of treatment. We use the scoring systems to predict the mortality risk of cryptococcal fungemia. This was a single hospital-based retrospective study on patients diagnosed with cryptococcal fungemia confirmed by at least one blood culture collected from the emergency department covering January 2012 and December 2020 from electronic medical records in the Taichung Veterans General Hospital. We enrolled 42 patients, including 28 (66.7%) males and 14 (33.3%) females with a mean age of 63.0 ± 19.7 years. The hospital stay ranged from 1 to 170 days (a mean stay of 44.4 days), and the overall mortality rate was 64.3% (27/42). In univariate analysis, the AUC of ROC for MEWS, RAPS, qSOFA, MEWS plus GCS, REMS, NEWS, and MEDS showed 0.833, 0.842, 0.848, 0.846, 0.846, 0.878, and 0.905. In the multivariate Cox regression analysis, all scoring systems, older age, lactate, MAP, and DBP, indicated significant differences between survivor and non-survivor groups. Our results show that all scoring systems could apply in predicting the outcome of patients with cryptococcal fungemia, and the MEDS displays the best performance. We recommend a further large-scale prospective study for patients with cryptococcal fungemia.

For medical data mining, the development of a class prediction model has been widely used to deal with various kinds of data classification problems. Classification models especially for high-dimensional gene expression datasets have attracted many researchers in order to identify marker genes for distinguishing any type of cancer cells from their corresponding normal cells. However, skewed class distributions often occur in the medical datasets in which at least one of the classes has a relatively small number of observations. A classifier induced by such an imbalanced dataset typically has a high accuracy for the majority class and poor prediction for the minority class. In this study, we focus on an SVM classifier with a Gaussian radial basis kernel for a binary classification problem. In order to take advantage of an SVM and to achieve the best generalization ability for improving the classification performance, we will address two important problems: the class imbalance and parameter selection during SVM parameter optimization. First of all, we proposed a novel adjustment method called b-SVM, for adjusting the cutoff threshold of the SVM. Second, we proposed a fast and simple approach, called the Min-max gamma selection, to optimize the model parameters of SVMs without carrying out an extensive k-fold cross validation. An extensive comparison with a standard SVM and well-known existing methods are carried out to evaluate the performance of our proposed algorithms using simulated and real datasets. The experimental results show that our proposed algorithms outperform the over-sampling techniques and existing SVM-based solutions. This study also shows that the proposed Min-max gamma selection is at least 10 times faster than the cross-validation selection based on the average running time on six real datasets.

Background: Emphysematous cystitis (EC) is a complicated urinary tract infection (UTI) characterized by gas formation within the bladder wall and lumen. Immunocompetent people are less likely to suffer from complicated UTIs, but EC usually occurs in women with poorly controlled diabetes mellitus (DM). Other risk factors of EC include recurrent UTI, neurogenic bladder disorder, blood supply disorders, and prolonged catheterization, but DM is still the most important of all aspects. Our study investigated clinical scores in predicting clinical outcomes of patients with EC. Our analysis is unique in predicting EC clinical outcomes by using scoring system performance., Materials and Methods: We retrospectively collected EC patient data from the electronic clinical database of Taichung Veterans General Hospital between January 2007 and December 2020. Urinary cultures and computerized tomography confirmed EC. In addition, we investigated the demographics, clinical characteristics, and laboratory data for analysis. Finally, we used a variety of clinical scoring systems as a predictor of clinical outcomes., Results: A total of 35 patients had confirmed EC, including 11 males (31.4%) and 24 females (68.6%), with a mean age of 69.1 ± 11.4 years. Their hospital stay averaged 19.9 ± 15.5 days. The in-hospital mortality rate was 22.9%. The Mortality in Emergency Department Sepsis (MEDS) score was 5.4 ± 4.7 for survivors and 11.8 ± 5.3 for non-survivors ( p = 0.005). For mortality risk prediction, the AUC of ROC was 0.819 for MEDS and 0.685 for Rapid Emergency Medicine Score (REMS). The hazard ratio of univariate and multivariate logistic regression analyses of REMS for EC patients was1.457 ( p = 0.011) and 1.374 ( p = 0.025), respectively., Conclusion: Physicians must pay attention to high-risk patients according to clinical clues and arrange imaging studies as soon as possible to confirm the diagnosis of EC. MEDS and REMS are helpful for clinical staff in predicting the clinical outcome of EC patients. If EC patients feature higher scores of MEDS (≥12) and REMS (≥10), they will have higher mortality.

Background: Emphysematous pyelonephritis (EPN) is a rare but severe necrotizing infection causing there to be gas in the pelvicalyceal system, renal parenchyma, and perirenal or pararenal space. Physicians should attend to EPN because of its life-threatening septic complications. The overall mortality rate has been reported to be as high as 20−40%. In addition, most patients had diabetes mellitus (DM) and obstructive uropathy. The most common isolated microorganism is Escherichia coli. This study aims to analyze the risk factors and performance of scoring systems in predicting the clinical outcomes of patients with EPN. Materials and Methods: We collected the data of patients with EPN in this single hospital-based retrospective study from the electronic medical records of Taichung Veterans General Hospital between January 2007 and December 2020. Radiological investigations of abdominal computed tomography (CT) confirmed the diagnosis of EPN. In addition, we analyzed demographics, clinical characteristics, and laboratory data. Finally, we used various scoring systems to predict clinical outcomes. Results: A total of fifty patients with EPN, whose diagnoses were confirmed through CT, were enrolled in the study. There were 18 males (36%) and 32 females (64%), with a mean age of 64.3 ± 11.3 years. The in-hospital mortality rate was 16%. A DM of 34 (68%) patients was the most common comorbidity. Fever was the most common symptom, found in 25 (50%) patients. The Mortality in Emergency Department Sepsis (MEDS) score was 4.64 ± 3.67 for survivors and 14.25 ± 5.34 for non-survivors (p < 0.001). The National Early Warning Score (NEWS) was 3.64 ± 2.33 for survivors and 7.13 ± 4.85 for non-survivors (p = 0.046). The Rapid Emergency Medicine Score (REMS) was 5.81 ± 1.97 for survivors and 9.13 ± 3.87 for non-survivors (p = 0.024). Regarding performance of mortality risk prediction, the AUC of ROC was 0.932 for MEDS, 0.747 for REMS, and 0.72 for NEWS. Conclusions: MEDS, REMS, and NEWS could be prognostic tools for the prediction of the clinical outcomes of patients with EPN. MEDS showed the best sound performance. In those with higher scores in MEDS (≥12), REMS (≥10), and NEWS (≥8), we recommended aggressive management and appropriate antimicrobial therapy as soon as possible to reduce mortality. Further large-scale studies are required to gain a deep understanding of this disease and to ensure patient safety.

Objective: Shewanella algae is a zoonotic marine bacterium that causes a variety of infections in immunocompromised patients or those who have been exposed to seawater. The development of trimethoprim/sulfamethoxazole (TMP/SMX) resistance in S. algae are found in human and environment isolates during the past ten years, and thus the treatment options are decreasing., Methodology: In the study, we conduct a comparative genomic study to identify the resistant mechanism of TMP/SMX-resistance in S. algae., Results: We found the resistance of TMP/SMX in S. algae is associated with the existence of sul1 and dfrA12 within the class 1 integron. The gene cassette dfra12-aadA2-qacEΔ1/sul1 within the class 1 integron is highly conserved. In addition, the class 1 integron and encapsulated sul1 are significantly enriched in Enterobacteriaceae in NCBI and UniProt databases., Conclusion: Our study suggests that the horizontal transfer of TMP/SMX resistance via class 1 integron is most frequently occurred within Enterobacteriaceae and has spread to a wide range of sources including soil, poultry, and marine water., Competing Interests: Declaration of competing interest None declared., (Copyright © 2021. Published by Elsevier B.V.)

Coronavirus disease 2019 (COVID-19) vaccines have proven to be safe, effective and life-saving. However, little information is available on the neurological complications of COVID-19 vaccine. Here, we report a case who developed acute encephalomyelitis 1 week after being vaccinated with AstraZeneca COVID-19 vaccine (AZ vaccine). Autoimmune/inflammatory syndrome induced by adjuvants (ASIA) was also suspected. After intravenous dexamethasone and subcutaneous fondaparinux therapy, he returned to normal life without neurological sequelae. Four months later, he received Moderna COVID-19 vaccine without any sequelae., (© 2022 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Background: Listeria monocytogenes (LM) is a facultative anaerobe, Gram-positive bacillus which is widely distributed in nature, and can be separated from soil, water, and rotten vegetables. Immunocompetent people are less likely to suffer from LM infection or may only show gastrointestinal symptoms. However, immunocompromised elderly people, pregnant women, and newborns may develop life-threatening invasive infections. The mortality rate of LM infection is as high as 25-30%. The aim of this study is to investigate clinical scores of patients with bacteremia of LM confirmed by one or more blood cultures. We analyzed their demographics and laboratory findings in relation to their clinical outcomes., Materials and Methods: This was a hospital-based retrospective study on patients with bacteremia of LM. Data were collected from the electronic clinical database of Taichung Veterans General Hospital between January 2012 and December 2020. Bacteremia of LM was confirmed by at least one blood culture. Demographics, clinical characteristics, and laboratory data were collected for analysis. A variety of clinical scoring systems were used to predict the clinical outcome., Results: A total of 39 patients had confirmed bacteremia of LM. Among them, 1 neonatal patient was excluded. The remaining 38 patients were studied. They included 16 males (42.1%) and 22 females (57.9%), with a mean age of 59.9 ± 19.6 years. Their hospital stay averaged 23.3 ± 20.9 days. The in-hospital mortality rate was 36.8%. Mortality in Emergency Department Sepsis (MEDS) Score was 6.6 ± 4.0 for survivors and 12.4 ± 4.4 for non-survivors (P < 0.001). The National Early Warning Score (NEWS) was 3.9 ± 2.8 for survivors and 7.8 ± 3.1 for non-survivors (P = 0.001). Regarding the prediction of mortality risk, the AUC of ROC was 0.829 for MEDS and 0.815 for NEWS., Conclusions: MEDS and NEWS were both good predictors of the clinical outcome in LM bacteremic patients. In those with higher scores of MEDS (≥10) and NEWS (≥8), we recommended an early goal-directed therapy and appropriate antibiotic treatment as early as possible to reduce mortality. Further large-scale studies are required to gain a deeper understanding of this disease and to ensure patient safety.

Background: Shewanella algae is a zoonotic pathogen that poses a serious health threat to immunocompromised hosts. Treatment of S. algae infections is challenging due to the pathogen's intrinsic resistance to a variety of β-lactam antibiotics. Therapeutic options have become further limited by the emergence of quinolone-resistant strains. Currently, there are few studies concerning the genetic and molecular mechanisms underlying acquired quinolones resistance in S. algae. qnrA was once proposed as the candidate gene related to quinolones resistance in S. algae. However, recent studies demonstrated qnrA are highly conservative and does not confer resistance to quinolones in S. algae., Methods: A total of 27 non-duplicated isolates of S. algae strains were examined. MICs of ciprofloxacin were determined using Vitek 2. Whole genome sequencing was performed using MiSeq platform. Comprehensive Antibiotic Resistance Database and ResFinder were used for annotation of quinolones resistance genes. Multiple sequence alignment by EMBOSS Clustal Omega were used to identified mutation in quinolone resistance-determining regions. To investigation of the alteration of protein structure induced by mutation, in silico molecular docking studies was conducted using Accryl Discovery studio visualizer., Results: All S. algae harbored the quinolone-resistance associated genes (qnrA, gyrA, gyrB, parC, and parE) regardless its resistance to ciprofloxacin. Comparison of these genomes identified a nonsynonymous mutation (S83V) in chromosome-encoded gyrase subunits (GyrA) in quinolone-resistant strain. We found this mutation disrupts the water-metal ion bridge, reduces the affinity of the quinolone-enzyme complex for the metal ions and therefore decrease the capability of quinolones to stabilize cleavage complexes., Conclusions: The study provides insight into the quinolone resistance mechanisms in S. algae, which would be helpful for the evolution of antibiotic resistance in this bacterium., (Copyright © 2020. Published by Elsevier B.V.)

In medical research, the development of mediation analysis with a survival outcome has facilitated investigation into causal mechanisms. However, studies have not discussed the death-truncation problem for mediators, the problem being that conventional mediation parameters cannot be well defined in the presence of a truncated mediator. In the present study, we systematically defined the completeness of causal effects to uncover the gap, in conventional causal definitions, between the survival and nonsurvival settings. We propose a novel approach to redefining natural direct and indirect effects, which are generalized forms of conventional causal effects for survival outcomes. Furthermore, we developed three statistical methods for the binary outcome of survival status and formulated a Cox model for survival time. We performed simulations to demonstrate that the proposed methods are unbiased and robust. We also applied the proposed method to explore the effect of hepatitis C virus infection on mortality, as mediated through hepatitis B viral load., (© 2021 John Wiley & Sons Ltd.)

During industrial-scale production of viruses for vaccine manufacturing, anti-viral response of host cells can dampen maximal viral antigen yield. In addition to interferon responses, many other cellular responses, such as the AMPK signaling pathway or senescence-like response may inhibit or slow down virus amplification in the cell culture system. In this study, we first performed a Gene Set Enrichment Analysis of the whole-genome mRNA transcriptome and found a senescence-like cellular response in BHK-21 cells when infected with bovine ephemeral fever virus (BEFV). To demonstrate that this senescence-like state may reduce virus growth, BHK-21 subclones showing varying degrees of a senescence-like state were infected with BEFV. The results showed that the BHK-21 subclones showing high senescence staining could inhibit BEFV replication while low senescence-staining subclones are permissive to virus replication. Using a different approach, a senescence-like state was induced in BHK-21 using a small molecule, camptothecin (CPT), and BEFV susceptibility were examined. The results showed that CPT-treated BHK-21 is more resistant to virus infection. Overall, these results indicate that a senescence-like response may be at play in BHK-21 upon virus infection. Furthermore, cell clone selection and modulating treatments using small molecules may be tools in countering anti-viral responses.

Protein kinase C (PKC) signaling is a highly conserved signaling module that plays a central role in a myriad of physiological processes, ranging from cell proliferation to cell death, via various signaling pathways, including MAPK signaling. Stress granules (SGs) are non-membranous cytoplasmic foci that aggregate in cells exposed to environmental stresses. Here, we explored the role of SGs in PKC/MAPK signaling activation in fission yeast. High-heat stress (HHS) induced Pmk1 MAPK activation and Pck2 translocation from the cell tips into poly(A)-binding protein (Pabp)-positive SGs. Pck2 dispersal from the cell tips required Pck2 kinase activity, and constitutively active Pck2 exhibited increased translocation to SGs. Importantly, Pmk1 deletion impaired Pck2 recruitment to SGs, indicating that MAPK activation stimulates Pck2 SG translocation. Consistently, HHS-induced SGs delayed Pck2 relocalization at the cell tips, thereby blocking subsequent Pmk1 reactivation after recovery from HHS. HHS partitioned Pck2 into the Pabp-positive SG-containing fraction, which resulted in reduced Pck2 abundance and kinase activity in the soluble fraction. Taken together, these results indicate that MAPK-dependent Pck2 SG recruitment serves as a feedback mechanism to intercept PKC/MAPK activation induced by HHS, which might underlie PKC-related diseases., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2021. Published by The Company of Biologists Ltd.)

Rapid identification of structural damage positions is essential to the post-disaster rehabilitation of structures and infrastructures. Large shear deformation, e.g., shear failure of bridge piers, shear-slip of slopes, and shear cracking of structural walls, is often the cause of structural instability. Distributed optical fibre sensing (DOFS) techniques have an advantage over point-based sensors in terms of spatial continuous structural condition monitoring. This paper presents the development of new measurement theory and algorithm to evaluate the structural shear deflection based on the large beam deflection and optical bend loss theories. The proposed technique adopted a photon-counting Optical Time Domain Reflectometer (ν-OTDR) with polymer optical fibres (POFs) which has a large deformation measurement range and high spatial resolution. In the experiment, shear deformation events can be successfully detected and evaluated from the proposed technique. When the normalised shear deformation is larger than 0.2, both the event locations and the magnitudes can be accurately determined. When normalised shear deformation is lesser than 0.2, the error in the magnitude evaluation increased, but the event location can be found with an absolute error <0.5 m. Multiple shear events can be treated as independent events when they are separated by more than 5 m. Various configurations of POFs attached to concrete beam specimens for rupture failure monitoring were also studied. The configuration that could maximise the POF curvature at the beam failure produced the largest ν-OTDR signals. In other configurations in which the POFs were only stretched at failure, the signals were less strong and were influenced by the POF-structure bonding strength.

Rationale: Renal actinomycosis is a rare clinical infection, subacute to chronic presentation caused by the Actinomyces bacteria. Actinomyces israelii is diagnosed in the overpowering majority of reported cases. Abdominopelvic manifestation forms 10% to 20% of all actinomycosis, and may be misdiagnosed as either a malignancy or chronic inflammation due to the lower correct preoperative diagnostic rate (<10%)., Patient Concerns: A 38-year-old man with alcoholic liver cirrhosis experienced right flank pain, abdominal pain, and fever for 3 days. Leukocytosis, acute kidney injury, and impaired liver function were found. A computed tomographic scan demonstrated multiple renal cystic lesions, along with fluid accumulation at the right subphrenic and retroperitoneal spaces., Diagnoses: Renal actinomycosis was confirmed via cultures of both the abscess and nephrectomy specimen which grew A israelii and the pathological findings of multiple renal abscesses of actinomycosis with the characteristics of sulfur granules., Interventions: A nephrectomy was performed for an inadequate percutaneous drainage of renal abscess., Outcomes: A full course of antibiotics with intravenous penicillin G (3 million units every 4 hours) was prescribed for 2 weeks, followed by oral penicillin V given at a dose of 2 grams per day for 6 months at our out-patient facility., Lessons: A precise diagnosis of primary renal actinomycosis depends on any histopathological findings and/or cultures of specimens. A high dose of intravenous penicillin G is the first choice, followed by oral penicillin V, with the duration of each being dependent upon the individual condition.

Objectives: The aim of this study was to determine the long-term incidence of cryptococcosis in kidney transplant recipients (KTRs) and to analyze its risk factors., Methods: This retrospective population-based cohort study analyzed data obtained from Taiwan's National Health Insurance Research Database for KTRs during 2000-2012 and matched cohorts. Both populations were followed until death, development of cryptococcosis, or December 2013., Results: A total of 4,933 KTRs and 49,930 matched patients were included. The cryptococcosis incidence rates for the KTR cohort and matched cohort were 10.59 and 0.4 per 10,000 person-years, respectively. The hazard ratio for cryptococcosis among KTRs was 26.65 (p<0.001); and 43.77 (p<0.001) for cryptococcosis affecting the central nervous system (CNS). The Kaplan-Meier method confirmed an elevated cumulative incidence of cryptococcosis among KTRs (1.00% vs. 0.04%). Predictors for cryptococcosis were advanced age (OR 1.39, 95% CI 1.02-1.89, P=0.038) and cancer (OR 2.63, 95% CI 1.22-5.67, P=0.013), but not the use of any particular class of immunosuppressants., Conclusions: KTRs are at dramatically higher risk of developing cryptococcosis, especially with CNS involvement, relative to a non-KTR matched cohort. Older KTRs and those with cancer are at even higher risk of developing cryptococcosis., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Rationale: Endograft infection following endovascular stent for aortic aneurysm is rare (0.6%-3%), but it results in high mortality rate of 25% to 88%., Patient Concerns: A 66-year-old hypertensive man underwent an endovascular stent graft for abdominal aortic aneurysm 18 months ago. Recurrent episodes of fever, chills, and abdominal fullness occurred 6 months ago before this admission. Laboratory data showed 20 mg/dL of C-reactive protein and abdominal computed tomography (CT) revealed an aortic endoleak at an urban hospital, so 4-day course of intravenous (IV) amoxicillin/clavulanic acid was given and he was discharged after fever subsided. He was admitted to our hospital due to fever, chills, and watery diarrhea for 1 day. Abdominal CT showed left psoas abscess associated with endograft infection. Blood culture grew Listeria monocytogenes., Diagnosis: Left psoas abscess associated with endograft infection caused by bacteremia of Listeria monocytogenes., Interventions: IV ampicillin with 8 days of synergistic gentamicin was prescribed and it created satisfactory response. Ampicillin was continued for 30 days and then shifted to IV co-trimoxazole for 12 days., Outcomes: He remained asymptomatic with a decline of CRP to 0.36 mg/dL and ESR to 39 mm/h. He was discharged on the 44th hospital day. Orally SMX/TMP was prescribed for 13.5 months., Lessons: Only few cases of aortic endograft infection caused by Listeria monocytogenes had been reported. In selected cases, particularly with smoldering presentations and high operative risk, endograft retention with a prolonged antimicrobial therapy seem plausible as an initial therapeutic option, complemented with percutaneous drainage or surgical debridement if necessary.

Background: Iliopsoas abscess (IPA) is a rare clinical entity and is difficult to diagnose due to its insidious onset and nonspecific symptoms. The association between IPA and cardiovascular disorders (CVD) has been rarely reported. Computed tomographic (CT) scan can provide a definitive diagnosis of IPA and associated foci of adjacent structures. IPA is a life-threatening condition, especially when associated with CVD., Materials and Methods: We conducted a hospital-based observational study of IPA associated with CVD. Data were collected from the electronic clinical database of Taichung Veterans General Hospital (1520-bed tertiary referral hospital in central Taiwan) between July 2007 and December 2017. The diagnosis of IPA associated with CVD was confirmed by classical findings on CT and transesophageal echocardiography with compatible clinical presentation and cultures from pus/tissue and blood., Results: Fifteen patients of IPA associated with CVD were studied. They included 12 males (80%) and 3 females (20%), with a mean age 63.2 ± 16.9 years (31-85 years). CVD included stent-graft/endograft infection of abdominal aortic aneurysm (AAA) (40%), primary mycotic AAA (33.3%), and infective endocarditis (26.7%). Staphylococcus aureus is the most common microorganism in pus/tissue cultures (n = 3, 37.5%) and in blood cultures (n = 6, 40%). The average length of hospital stay was 33.1 ± 20.5 days (range, 3-81 days; median, 33 days). Hospital stay lasted 42.6 ± 19.2 days in the survival group and 19.0 ± 14.1 days (P = 0.018) in the non-survival group. Incidence of patients staying in the intensive care unit (ICU) with intubation > 3 days was 33% in the survival group and 100% (P = 0.028) in the non-survival group. Intra-hospital mortality rate was 40%. Poor prognostic factors in the non-survival group were hypoalbuminemia, hyponatremia, involved disc/vertebral body and/or epidural abscess, and ICU stay with intubation > 3 days. Cumulative survival rate was 25% under conservative treatments and 66.3% under aggressive treatments (P = 0.038)., Conclusion: Due to high mortality rates, clinicians should keep a high suspicion index for IPA associated with CVD through clinical presentation, physical examination, and imaging study. Timely empiric antibiotics for common bacteria, drainage for IPA, endovascular repair, or vascular reconstruction by graft replacement or bypass with intensive care should be mandatory to shorten the hospital stay, reduce medical costs, and lower mortality rate.

For survival endpoints in subgroup selection, a score conversion model is often used to convert the set of biomarkers for each patient into a univariate score and using the median of the univariate scores to divide the patients into biomarker-positive and biomarker-negative subgroups. However, this may lead to bias in patient subgroup identification regarding the 2 issues: (1) treatment is equally effective for all patients and/or there is no subgroup difference; (2) the median value of the univariate scores as a cutoff may be inappropriate if the sizes of the 2 subgroups are differ substantially. We utilize a univariate composite score method to convert the set of patient's candidate biomarkers to a univariate response score. We propose applying the likelihood ratio test (LRT) to assess homogeneity of the sampled patients to address the first issue. In the context of identification of the subgroup of responders in adaptive design to demonstrate improvement of treatment efficacy (adaptive power), we suggest that subgroup selection is carried out if the LRT is significant. For the second issue, we utilize a likelihood-based change-point algorithm to find an optimal cutoff. Our simulation study shows that type I error generally is controlled, while the overall adaptive power to detect treatment effects sacrifices approximately 4.5% for the simulation designs considered by performing the LRT; furthermore, the change-point algorithm outperforms the median cutoff considerably when the subgroup sizes differ substantially., (Copyright © 2018 John Wiley & Sons, Ltd.)

Genome-wide association studies (GWAS) have been a powerful tool for exploring potential relationships between single-nucleotide polymorphisms (SNPs) and biological traits. For screening out important genetic variants, it is desired to perform an exhaustive scan over a whole genome. However, this is usually a challenging and daunting task in computation, due mainly to the large number of SNPs in GWAS. In this article, we propose a computationally effective algorithm for highly homozygous genomes. Pseudo standard error (PSE) is known to be a highly efficient and robust estimator for the standard deviation of a quantitative trait. We thus develop a statistical testing procedure for determining significant SNP main effects and SNP × SNP interactions associated with a quantitative trait based on PSE. A simulation study is first conducted to evaluate its empirical size and power. It is shown that the proposed PSE-based method can generally maintain the empirical size sufficiently close to the nominal significance level. However, the power investigation indicates that the PSE-based method might lack power in identifying significant effects for low-frequency variants if their true effect sizes are not large enough. A software is provided for implementing the proposed algorithm and its computational efficiency is evaluated through another simulation study. An exhaustive scan is usually done within a very reasonable runtime and a rice genome data set is analyzed by the software.

In search of high-performance field-effect transistors (FETs) made of atomic thin semiconductors, indium selenide (InSe) has held great promise because of its high intrinsic mobility and moderate electronic band gap (1.26 eV). Yet the performance of InSe FETs is decisively determined by the surface oxidation of InSe taking place spontaneously in ambient conditions, setting up a mobility ceiling and causing an uncontrollable current hysteresis. Encapsulation by hexagonal boron nitride (h-BN) has been currently used to cope with this deterioration. Here, we provide insights into the role of surface oxides played in device performance and introduce a dry-oxidation process that forms a dense capping layer on top, where InSe FETs exhibit a record-high two-probe mobility of 423 cm 2 /V·s at room temperature and 1006 cm 2 /V·s at liquid nitrogen temperature without the use of h-BN encapsulation or high-κ dielectric screening. Ultrahigh on/off current ratio of >10 8 and current density of 365 μA/μm can be readily achieved without elaborate engineering of drain/source contacts or gating technique. Thickness-dependent device properties are also studied, with optimized performance shown in FETs comprising of 13 nm thick InSe. The high performance of InSe FETs with ultrathin dry oxide is attributed to the effective unpinning of the Fermi level at the metal contacts, resulting in a low Schottky barrier height of 40 meV in an optimized channel thickness.

Prostatic abscess is a rare entity with an incidence of 0.5%-2.5% in all prostate diseases and usually occurs in the 5th and 6th decades of life with immunocompromised status. Prostatic abscess might be a process of evolution from acute prostatitis. Klebsiella pneumoniae is the leading microorganism in the diabetic patients of prostatic abscess in Taiwan. A 60-year-old diabetic man, with a one-week history of acute bacterial prostatitis was reported in this study, presenting to the emergency department with sudden altered mental status. The abdominal computed tomographic scan demonstrated lobulated prostatic abscess and multiple septic pulmonary emboli with lung abscesses. Analysis of cerebrospinal fluid showed white blood cells of 10771 counts/mm 3 with segmented neutrophils of 99%. Cultures of blood, cerebrospinal fluid and sputum yielded Klebsiella pneumoniae. We concluded that computed tomographic scan can make a definite diagnosis of prostatic abscess associated with complications and management with empiric antibiotics and adequate drainage is suggested., (Copyright © 2017 Hainan Medical University. Production and hosting by Elsevier B.V. All rights reserved.)

A key feature of precision medicine is that it takes individual variability at the genetic or molecular level into account in determining the best treatment for patients diagnosed with diseases detected by recently developed novel biotechnologies. The enrichment design is an efficient design that enrolls only the patients testing positive for specific molecular targets and randomly assigns them for the targeted treatment or the concurrent control. However there is no diagnostic device with perfect accuracy and precision for detecting molecular targets. In particular, the positive predictive value (PPV) can be quite low for rare diseases with low prevalence. Under the enrichment design, some patients testing positive for specific molecular targets may not have the molecular targets. The efficacy of the targeted therapy may be underestimated in the patients that actually do have the molecular targets. To address the loss of efficiency due to misclassification error, we apply the discrete mixture modeling for time-to-event data proposed by Eng and Hanlon [8] to develop an inferential procedure, based on the Cox proportional hazard model, for treatment effects of the targeted treatment effect for the true-positive patients with the molecular targets. Our proposed procedure incorporates both inaccuracy of diagnostic devices and uncertainty of estimated accuracy measures. We employed the expectation-maximization algorithm in conjunction with the bootstrap technique for estimation of the hazard ratio and its estimated variance. We report the results of simulation studies which empirically investigated the performance of the proposed method. Our proposed method is illustrated by a numerical example.

Background: Gene set analysis (GSA) aims to evaluate the association between the expression of biological pathways, or a priori defined gene sets, and a particular phenotype. Numerous GSA methods have been proposed to assess the enrichment of sets of genes. However, most methods are developed with respect to a specific alternative scenario, such as a differential mean pattern or a differential coexpression. Moreover, a very limited number of methods can handle either binary, categorical, or continuous phenotypes. In this paper, we develop two novel GSA tests, called SDRs, based on the sufficient dimension reduction technique, which aims to capture sufficient information about the relationship between genes and the phenotype. The advantages of our proposed methods are that they allow for categorical and continuous phenotypes, and they are also able to identify a variety of enriched gene sets., Results: Through simulation studies, we compared the type I error and power of SDRs with existing GSA methods for binary, triple, and continuous phenotypes. We found that SDR methods adequately control the type I error rate at the pre-specified nominal level, and they have a satisfactory power to detect gene sets with differential coexpression and to test non-linear associations between gene sets and a continuous phenotype. In addition, the SDR methods were compared with seven widely-used GSA methods using two real microarray datasets for illustration., Conclusions: We concluded that the SDR methods outperform the others because of their flexibility with regard to handling different kinds of phenotypes and their power to detect a wide range of alternative scenarios. Our real data analysis highlights the differences between GSA methods for detecting enriched gene sets.

Studies of Alzheimer's disease (AD) have predominantly focused on two major pathologies: amyloid-β (Aβ) and hyperphosphorylated tau. These misfolded proteins can accumulate asymptomatically in distinct regions over decades. However, significant Aβ accumulation can be seen in individuals who do not develop dementia, and tau pathology limited to the transentorhinal cortex, which can appear early in adulthood, is usually clinically silent. Thus, an interaction between these pathologies appears to be necessary to initiate and propel disease forward to widespread circuits. Recent multidisciplinary findings strongly suggest that the third factor required for disease progression is an aberrant microglial immune response. This response may initially be beneficial; however, a maladaptive microglial response eventually develops, fueling a feed-forward spread of tau and Aβ pathology., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

We apply the concept of spoof surface plasmon polaritons (SPPs) to the design of differential microstrip lines by introducing periodic subwavelength corrugations on their edges. The dispersion relation and field distribution of those lines are analyzed numerically. And then through designing practical coupling circuits, we found that compared with conventional differential microstrip lines, the electromagnetic field can be strongly confined inside the grooves of the corrugated microstrip lines, so the crosstalk between the differential pair and the adjacent microstrip lines is greatly reduced, and the conversion from the differential signal to the common mode signal can also be effectively suppressed. The propagation length of those lines is also very long in a wide band. Moreover, the experimental results in time domain demonstrate those lines perform very well in high-speed circuit. Therefore, those novel kinds of spoof SPPs based differential microstrip lines can be widely utilized in high-density microwave circuits and guarantee signal integrity in high-speed systems.

The approval of generic drugs requires the evidence of average bioequivalence (ABE) on both the area under the concentration-time curve and the peak concentration Cmax . The bioequivalence (BE) hypothesis can be decomposed into the non-inferiority (NI) and non-superiority (NS) hypothesis. Most of regulatory agencies employ the two one-sided tests (TOST) procedure to test ABE between two formulations. As it is based on the intersection-union principle, the TOST procedure is conservative in terms of the type I error rate. However, the type II error rate is the sum of the type II error rates with respect to each null hypothesis of NI and NS hypotheses. When the difference in population means between two treatments is not 0, no close-form solution for the sample size for the BE hypothesis is available. Current methods provide the sample sizes with either insufficient power or unnecessarily excessive power. We suggest an approximate method for sample size determination, which can also provide the type II rate for each of NI and NS hypotheses. In addition, the proposed method is flexible to allow extension from one pharmacokinetic (PK) response to determination of the sample size required for multiple PK responses. We report the results of a numerical study. An R code is provided to calculate the sample size for BE testing based on the proposed methods., (Copyright © 2014 John Wiley & Sons, Ltd.)

Background: Studies indicate that asymptomatic infections do indeed occur frequently for both seasonal and pandemic influenza, accounting for about one-third of influenza infections. Studies carried out during the 2009 pH1N1 pandemic have found significant antibody response against seasonal H1N1 and H3N2 vaccine strains in schoolchildren receiving only pandemic H1N1 monovalent vaccine, yet reported either no symptoms or only mild symptoms., Methods: Serum samples of 255 schoolchildren, who had not received vaccination and had pre-season HI Ab serotiters <40, were collected from urban, rural areas and an isolated island in Taiwan during the 2005-2006 influenza season. Their hemagglutination inhibition antibody (HI Ab) serotiters against the 2005 A/New Caledonia/20/99 (H1N1) vaccine strain at pre-season and post-season were measured to determine the symptoms with the highest correlation with infection, as defined by 4-fold rise in HI titer. We estimate the asymptomatic ratio, or the proportion of asymptomatic infections, for schoolchildren during the 2005-6 influenza season when this vaccine strain was found to be antigenically related to the circulating H1N1 strain., Results: Fever has the highest correlation with the 2005-06 seasonal influenza A(H1N1) infection, followed by headache, cough, vomiting, and sore throat. Asymptomatic ratio for the schoolchildren is found to range between 55.6% (95% CI: 44.7-66.4)-77.9% (68.8-87.0) using different sets of predictive symptoms. Moreover, the asymptomatic ratio was 66.9% (56.6-77.2) when using US-CDC criterion of fever + (cough/sore throat), and 73.0 (63.3-82.8) when under Taiwan CDC definition of Fever + (cough or sore throat or nose) + ( headache or pain or fatigue)., Conclusions: Asymptomatic ratio for children is found to be substantially higher than that of the general population in literature. In providing reasonable quantification of the asymptomatic infected children spreading pathogens to others in a seasonal epidemic or a pandemic, our estimates of symptomatic ratio of infected children has important clinical and public health implications.

Nontyphoidal Salmonella infections often present with self-limited gastroenteritis. Extraintestinal focal infections are uncommon but have high mortality and morbidity. Urinary tract infection caused by nontyphoidal Salmonella is usually associated with structural abnormalities of the urinary tract. Nephrocalcinosis and nephrolithiasis are the major risk factors. Although primary hyperparathyroidism has been reported to increase the risk of nephrocalcinosis and nephrolithiasis, little is known about the association between hyperparathyroidism and Salmonella urinary tract infection. We report the case of a 37-year old man who had a history of primary hyperparathyroidism and bilateral nephrocalcinosis and who developed urinary tract infection. Salmonella Group D was isolated from his urine specimen. Salmonella should be considered as a possible causality organism in patients with primary hyperparathyroidism and nephrocalcinosis who develop urinary tract infection. These patients need to be aware of the potential risks associated with salmonellosis.

Gene set analysis methods aim to determine whether an a priori defined set of genes shows statistically significant difference in expression on either categorical or continuous outcomes. Although many methods for gene set analysis have been proposed, a systematic analysis tool for identification of different types of gene set significance modules has not been developed previously. This work presents an R package, called MAVTgsa, which includes three different methods for integrated gene set enrichment analysis. (1) The one-sided OLS (ordinary least squares) test detects coordinated changes of genes in gene set in one direction, either up- or downregulation. (2) The two-sided MANOVA (multivariate analysis variance) detects changes both up- and downregulation for studying two or more experimental conditions. (3) A random forests-based procedure is to identify gene sets that can accurately predict samples from different experimental conditions or are associated with the continuous phenotypes. MAVTgsa computes the P values and FDR (false discovery rate) q-value for all gene sets in the study. Furthermore, MAVTgsa provides several visualization outputs to support and interpret the enrichment results. This package is available online.

Background: Percutaneous drainage (PCD) and surgical intervention are two primary treatment options for iliopsoas abscess (IPA). However, there is currently no consensus on when to use PCD or surgical intervention, especially in patients with gas-forming IPA. This study compared the characteristics of patients with gas-forming and non-gas forming IPA and their mortality rates under different treatment modalities. An algorithm for selecting appropriate treatment for IPA patients is proposed based on our findings., Methods: Eighty-eight IPA patients between July 2007 and February 2013 were enrolled in this retrospective study. Patients < 18 years of age or with an incomplete course of treatment were excluded. Demographic information, clinical characteristics, and outcomes of different treatment approaches were compared between gas-forming IPA and non-gas forming IPA patients., Results: Among the 88 enrolled patients, 27 (31%) had gas-forming IPA and 61 (69%) had non-gas forming IPA. The overall intra-hospital mortality rate was 25%. The gas-forming IPA group had a higher intra-hospital mortality rate (12/27, 44.0%) than the non-gas forming IPA group (10/61, 16.4%) (P < 0.001). Only 2 of the 13 patients in the gas-forming IPA group initially accepting PCD had a good outcome (success rate = 15.4%). Three of the 11 IPA patients with failed initial PCD expired, and 8 of the 11 patients with failed initial PCD accepted salvage operation, of whom 5 survived. Seven of the 8 gas-forming IPA patients accepting primary surgical intervention survived (success rate = 87.5%). Only 1 of the 6 gas-forming IPA patients who accepted antibiotics alone, without PCD or surgical intervention, survived (success rate = 16.7%). In the non-gas forming IPA group, 23 of 61 patients initially accepted PCD, which was successful in 17 patients (73.9%). The success rate of PCD was much higher in the non-gas forming group than in the gas-forming group (P <0.01)., Conclusions: Based on the high failure rate of PCD and the high success rate of surgical intervention in our samples, we recommend early surgical intervention with appropriate antibiotic treatment for the patients with gas-forming IPA. Either PCD or primary surgical intervention is a suitable treatment for patients with non-gas forming IPA.

Shift work or transmeridian travel can desynchronize the body's circadian rhythms from local light-dark cycles. The mammalian suprachiasmatic nucleus (SCN) generates and entrains daily rhythms in physiology and behavior. Paradoxically, we found that vasoactive intestinal polypeptide (VIP), a neuropeptide implicated in synchrony among SCN cells, can also desynchronize them. The degree and duration of desynchronization among SCN neurons depended on both the phase and the dose of VIP. A model of the SCN consisting of coupled stochastic cells predicted both the phase- and the dose-dependent response to VIP and that the transient phase desynchronization, or "phase tumbling", could arise from intrinsic, stochastic noise in small populations of key molecules (notably, Period mRNA near its daily minimum). The model also predicted that phase tumbling following brief VIP treatment would accelerate entrainment to shifted environmental cycles. We tested this using a prepulse of VIP during the day before a shift in either a light cycle in vivo or a temperature cycle in vitro. Although VIP during the day does not shift circadian rhythms, the VIP pretreatment approximately halved the time required for mice to reentrain to an 8-h shifted light schedule and for SCN cultures to reentrain to a 10-h shifted temperature cycle. We conclude that VIP below 100 nM synchronizes SCN cells and above 100 nM reduces synchrony in the SCN. We show that exploiting these mechanisms that transiently reduce cellular synchrony before a large shift in the schedule of daily environmental cues has the potential to reduce jet lag.

In DNA microarray studies, gene-set analysis (GSA) has become the focus of gene expression data analysis. GSA utilizes the gene expression profiles of functionally related gene sets in Gene Ontology (GO) categories or priori-defined biological classes to assess the significance of gene sets associated with clinical outcomes or phenotypes. Many statistical approaches have been proposed to determine whether such functionally related gene sets express differentially (enrichment and/or deletion) in variations of phenotypes. However, little attention has been given to the discriminatory power of gene sets and classification of patients. In this study, we propose a method of gene set analysis, in which gene sets are used to develop classifications of patients based on the Random Forest (RF) algorithm. The corresponding empirical p-value of an observed out-of-bag (OOB) error rate of the classifier is introduced to identify differentially expressed gene sets using an adequate resampling method. In addition, we discuss the impacts and correlations of genes within each gene set based on the measures of variable importance in the RF algorithm. Significant classifications are reported and visualized together with the underlying gene sets and their contribution to the phenotypes of interest. Numerical studies using both synthesized data and a series of publicly available gene expression data sets are conducted to evaluate the performance of the proposed methods. Compared with other hypothesis testing approaches, our proposed methods are reliable and successful in identifying enriched gene sets and in discovering the contributions of genes within a gene set. The classification results of identified gene sets can provide an valuable alternative to gene set testing to reveal the unknown, biologically relevant classes of samples or patients. In summary, our proposed method allows one to simultaneously assess the discriminatory ability of gene sets and the importance of genes for interpretation of data in complex biological systems. The classifications of biologically defined gene sets can reveal the underlying interactions of gene sets associated with the phenotypes, and provide an insightful complement to conventional gene set analyses., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Gene set testing problem has become the focus of microarray data analysis. A gene set is a group of genes that are defined by a priori biological knowledge. Several statistical methods have been proposed to determine whether functional gene sets express differentially (enrichment and/or deletion) in variations of phenotypes. However, little attention has been given to analyzing the dependence structure among gene sets. In this study, we have proposed a novel statistical method of gene set association analysis to identify significantly associated gene sets using the coefficient of intrinsic dependence. The simulation studies show that the proposed method outperforms the conventional methods to detect general forms of association in terms of control of type I error and power. The correlation of intrinsic dependence has been applied to a breast cancer microarray dataset to quantify the un-supervised relationship between two sets of genes in the tumor and non-tumor samples. It was observed that the existence of gene-set association differed across various clinical cohorts. In addition, a supervised learning was employed to illustrate how gene sets, in signaling transduction pathways or subnetworks regulated by a set of transcription factors, can be discovered using microarray data. In conclusion, the coefficient of intrinsic dependence provides a powerful tool for detecting general types of association. Hence, it can be useful to associate gene sets using microarray expression data. Through connecting relevant gene sets, our approach has the potential to reveal underlying associations by drawing a statistically relevant network in a given population, and it can also be used to complement the conventional gene set analysis.

Background: The status of immunocompromised patients is well recognized in end stage renal disease (ESRD). As described recently, this acquired immune dysfunction in the uremic milieu may be one of the main pathogenic factors for mortality in ESRD. The aim of this study was to determine the relationship between the immune response following a hepatitis B vaccination (HBV vaccination) and the survival of maintenance dialysis patients., Methods: A total of 156 patients (103 on hemodialysis and 53 on continuous ambulatory peritoneal dialysis) were recruited. After receiving a full dose of the HBV vaccination, all patients were followed up for to 5 years to evaluate the association of patient survival, cause of mortality, and immune response., Results: The response rate to the hepatitis B vaccination was 70.5%. There was no significant association between the immune response and the 5-year survival rate (p =0.600) or between the post-vaccination anti-HBs titers and the 5-year survival rate (p = 0.201). The logistic prediction model with the coefficient as non-response following HBV vaccination, diabetes mellitus, old age, and low albumin level could significantly predict infection-cause mortality (sensitivity = 0.842, specificity = 0.937)., Conclusion: There was no significant association between the immune response to HBV vaccination and the 5-year survival rate. However, non-response following HBV vaccination might be associated with infection-cause mortality in dialysis patients.

Franklin disease, or gamma heavy-chain disease, in patients with autoimmune disorders is a challenge for clinicians to diagnose due to its rarity, and recurrent infection is one of its characteristics. Within the spectrum of infections in Franklin disease patients, various fungi should always be considered. In this study, the authors describe a 57-year-old non-human immunodeficiency virus-infected systemic lupus erythematosus patient later diagnosed with Franklin disease and then developed Penicillium pneumonia. Because of the unexpected combination of Franklin disease and Penicillium infection in a non-human immunodeficiency virus-infected patient, the diagnosis of common hospital-acquired pneumonia was initially made. The laboratory examinations and cultures helped confirm the correct diagnosis of Franklin disease and Penicillium pneumonia. This is the first report of Penicillium sp. infection in a patient with Franklin disease, and it emphasizes the importance of proper preparation for biopsy, complete hematologic investigation, culture preparation and early antifungal coverage to improve the outcome.

The development of DNA microarray makes researchers screen thousands of genes simultaneously and it also helps determine high- and low-expression level genes in normal and disease tissues. Selecting relevant genes for cancer classification is an important issue. Most of the gene selection methods use univariate ranking criteria and arbitrarily choose a threshold to choose genes. However, the parameter setting may not be compatible to the selected classification algorithms. In this paper, we propose a new gene selection method (SVM-t) based on the use of t-statistics embedded in support vector machine. We compared the performance to two similar SVM-based methods: SVM recursive feature elimination (SVMRFE) and recursive support vector machine (RSVM). The three methods were compared based on extensive simulation experiments and analyses of two published microarray datasets. In the simulation experiments, we found that the proposed method is more robust in selecting informative genes than SVMRFE and RSVM and capable to attain good classification performance when the variations of informative and noninformative genes are different. In the analysis of two microarray datasets, the proposed method yields better performance in identifying fewer genes with good prediction accuracy, compared to SVMRFE and RSVM.

Objective: The focus of this study was to ascertain the factors associated with 2009 pandemic influenza H1N1 (pH1N1) infection during different phases of the epidemic., Methods: In central Taiwan, 306 persons from households with schoolchildren were followed sequentially and serum samples were taken at three sampling time-points starting in the fall of 2008, shortly after influenza vaccination. Participants who seroconverted between two consecutive blood samplings were considered as having serological evidence of infection. A generalized estimation equation (GEE) with a logistic link to account for household correlations was applied to identify factors associated with pH1N1 infections during the pre-epidemic (April-June) and epidemic (September-October) periods., Results: The results showed that receiving an inactivated seasonal influenza vaccine (ISIV) and having a hemagglutination inhibition assay (HI) titer of 40 or higher resulted in a significantly lower likelihood of pH1N1 infection during the pre-epidemic period only, for both children and adults (adjusted odds ratio (OR) 0.3, 95% confidence interval (CI) 0.12-0.9). Having a previous infection by pH1N1 with a baseline titer of 20 or higher resulted in a significantly lower likelihood of infection by pH1N1 during the epidemic period (adjusted OR 0.06, 95% CI 0.02-0.16)., Conclusions: Our results provide the first serological evidence to suggest a protection effect from receiving an ISIV against pH1N1 infection only when the HI titer reaches 40 or higher during the pre-epidemic period. This study gives an important insight into the control and intervention measures required for preventing infections during future influenza epidemics., (Copyright © 2011 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: Several lines of evidence implicate glutamatergic neurotransmission in the pathophysiology of obsessive compulsive disorder (OCD). Sarcosine is an endogenous antagonist of glycine transporter-1. By blocking glycine uptake, sarcosine may increase the availability of synaptic glycine and enhance N-methyl-d-aspartate (NMDA) subtype glutamatergic neurotransmission. In this 10-week open-label trial, we examined the potential benefit of sarcosine treatment in OCD patients., Method: Twenty-six outpatients with OCD and baseline Yale-Brown Obsessive Compulsive Scale (YBOCS) scores higher than 16 were enrolled. Drug-naive subjects (group 1, n = 8) and those who had discontinued serotonin reuptake inhibitors for at least 8 weeks at study entry (group 2, n = 6) received sarcosine monotherapy. The other subjects (group 3, n = 12) received sarcosine as adjunctive treatment. A flexible dosage schedule of sarcosine 500 to 2000 mg/d was applied. The primary outcome measures were Y-BOCS and Hamilton Anxiety Inventory, rated at weeks 0, 2, 4, 6, 8, and 10. Results were analyzed by repeated-measures analysis of variance., Results: Data of 25 subjects were eligible for analysis. The mean ± SD Y-BOCS scores decreased from 27.6 ± 5.8 to 22.7 ± 8.7, indicating a mean decrease of 19.8% ± 21.7% (P = 0.0035). Eight (32%) subjects were regarded as responders with greater than 35% reduction of Y-BOCS scores. Five of the responders achieved the good response early by week 4. Although not statistically significant, drug-naive (group 1) subjects had more profound and sustained improvement and more responders than the subjects who had received treatment before (groups 2 and 3). Sarcosine was tolerated well; only one subject withdrew owing to transient headache., Conclusion: Sarcosine treatment can achieve a fast therapeutic effect in some OCD patients, particularly those who are treatment naive. The study supports the glycine transporter-1 as a novel target for developing new OCD treatment. Large-series placebo-controlled, double-blind studies are recommended.

Background and Objectives: The available information about maintaining effective immunity after hepatitis B virus (HBV) vaccination in dialysis patients is limited. The aim of this study was to determine whether a difference exists in the persistence of immunity between hemodialysis (HD) and peritoneal dialysis (PD) patients. We compared the decay rate of hepatitis B surface antibody (anti-HBs) titers after HBV vaccination between HD and PD patients., Design, Setting, Participants, and Measures: A total of 103 HD and 53 PD patients who were completely vaccinated were enrolled. We examined their anti-HBs titers at the 1st month after vaccination then annually thereafter. Changes in the anti-HBs titers were assessed by comparing annual geometric mean titers (GMTs)., Results: The slopes of the anti-HBs titer decay rates plotted on a logarithmic scale for the HD and PD groups were -23.41 and -31.48, respectively. The decay rate of the PD group was significantly faster than that of the HD group (P=0.0053)., Conclusion: The decay rate of anti-HBs titers in the PD group was faster than that in the HD group. Hepatitis B vaccination could not offer long-term protection in HD or PD patients. Post-vaccination testing every 6-12 months is necessary and revaccination may be protective in dialysis patients, especially in hyper-endemic areas of hepatitis B infection., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Background: Relying on surveillance of clinical cases limits the ability to understand the full impact and severity of an epidemic, especially when subclinical cases are more likely to be present in the early stages. Little is known of the infection and transmissibility of the 2009 H1N1 pandemic influenza (pH1N1) virus outside of Mexico prior to clinical cases being reported, and of the knowledge pertaining to immunity and incidence of infection during April-June, which is essential for understanding the nature of viral transmissibility as well as for planning surveillance and intervention of future pandemics., Methodology/principal Findings: Starting in the fall of 2008, 306 persons from households with schoolchildren in central Taiwan were followed sequentially and serum samples were taken in three sampling periods for haemagglutination inhibition (HI) assay. Age-specific incidence rates were calculated based on seroconversion of antibodies to the pH1N1 virus with an HI titre of 1:40 or more during two periods: April-June and September-October in 2009. The earliest time period with HI titer greater than 40, as well as a four-fold increase of the neutralization titer, was during April 26-May 3. The incidence rates during the pre-epidemic phase (April-June) and the first wave (July-October) of the pandemic were 14.1% and 29.7%, respectively. The transmissibility of the pH1N1 virus during the early phase of the epidemic, as measured by the effective reproductive number R(0), was 1.16 (95% confidence interval (CI): 0.98-1.34)., Conclusions: Approximately one in every ten persons was infected with the 2009 pH1N1 virus during the pre-epidemic phase in April-June. The lack of age-pattern in seropositivity is unexpected, perhaps highlighting the importance of children as asymptomatic transmitters of influenza in households. Although without virological confirmation, our data raise the question of whether there was substantial pH1N1 transmission in Taiwan before June, when clinical cases were first detected by the surveillance network.

The serological response of the current 2009 H1N1 pandemic influenza monovalent vaccine in children exhibiting high baseline seropositive rate was evaluated though a community-based household study. Seroprotection rate of >90% and seroconversion rate of >50% were observed in children one month after receiving the pandemic vaccine. Among children with low baseline antibody titer, a significant lower seroconversion rate (55%) was observed in children who received seasonal trivalent inactivated vaccine (TIV) prior to pandemic vaccine, when compared with those receiving the pandemic vaccine only (86%). Persistence of antibody against the pandemic influenza virus was observed 6 months after vaccination in >80% of children presenting seroprotective antibody levels., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Actinomycosis is an uncommon, chronic, granulomatous disease caused by several species of the genus Actinomyces, a Gram-positive, filamentous bacterium that normally colonizes mucosal areas. Actinomycosis can be mistaken for malignant tumors, and in most cases the diagnosis is delayed or missed entirely until surgery. Actinomycosis in the abdomen or pelvis mostly results from prolonged use of an intrauterine device. We report the case of a 40-year-old female who presented with decreased urine production, poor appetite, marked loss of body weight and intermittent lower abdominal pain for 3 months. Abdominal computed tomography indicated a large infiltrative pelvic mass that was complicated by bilateral hydronephrosis, bladder compression and small bowel adhesions. Despite the elevated levels of cancer antigen 125, we suspected pelvic actinomycosis because of a 15-year history of an intrauterine device. The diagnosis was confirmed by histopathological examination of soft tissue obtained from a laparotomy biopsy. We successfully treated the patient with prolonged antibiotics instead of surgical eradication. Abdominal computed tomography obtained 1 year later showed almost complete resolution of the pelvic inflammatory mass., (Copyright © 2010 Taiwan Society of Microbiology. Published by Elsevier B.V. All rights reserved.)

Recent development of high-throughput technology has accelerated interest in the development of molecular biomarker classifiers for safety assessment, disease diagnostics and prognostics, and prediction of response for patient assignment. This article reviews and evaluates some important aspects and key issues in the development of biomarker classifiers. Development of a biomarker classifier for high-throughput data involves two components: (i) model building and (ii) performance assessment. This article focuses on feature selection in model building and cross validation for performance assessment. A 'frequency' approach to feature selection is presented and compared to the 'conventional' approach in terms of the predictive accuracy and stability of the selected feature set. The two approaches are compared based on four biomarker classifiers, each with a different feature selection method and well-known classification algorithm. In each of the four classifiers the feature predictor set selected by the frequency approach is more stable than the feature set selected by the conventional approach.

Objective: Abnormality of bone mineral metabolism is a common complication in chronic liver disease and/or chronic renal disease patients. We designed this study to evaluate the relationship between chronic hepatitis B infection and bone mineral metabolism in peritoneal dialysis patients., Patients and Methods: Serum calcium[adj], phosphorus, calcium and phosphorus product (Ca x P), along with intact parathyroid hormone (iPTH) levels were compared in peritoneal dialysis patients with and without chronic hepatitis B infection., Results: A total of 220 patients (142 female, 78 male) with a mean age of 56.30 +/- 14.28 (range 19 - 86) years old were recruited, 23 showed chronic hepatitis B infection and 197 showed none. No statistically significant difference in serum calcium[adj] levels (9.90 +/- 0.85 mg/dl vs. 10.08 +/- 0.80 mg/dl, p = 0.354), phosphorus levels (5.26 +/- 1.58 mg/dl vs. 5.21 +/- 1.35 mg/dl, p = 0.879) and calcium and phosphorus product (Ca x P) (52.23 +/- 17.54 mg(2)/dl(2) vs. 52.42 +/- 14.16 mg(2)/dl(2), p = 0.960) between groups with and without chronic hepatitis B infection was observed. Serum iPTH levels were significantly lower in chronic hepatitis B patients (median 143 pg/ml, range 3.42 - 889) than in the control group (median 235 pg/ml, range 3 - 2381) (p = 0.035). As analyzed by multi-variable linear regression, chronic hepatitis B was a predictor of lower serum iPTH levels (beta = -0.271; p = 0.030) after adjustments for age, gender, serum calcium and phosphorus levels and diabetes., Conclusion: No significant difference in serum calcium[adj]), phosphorus and calcium and phosphorus product (Ca x P) levels appeared between peritoneal dialysis patients with and without chronic hepatitis B infection. Serum iPTH levels proved to be definitely lower in chronic hepatitis B infection patients.

Motivation: Gene class testing (GCT) or gene set analysis (GSA) is a statistical approach to determine whether some functionally predefined sets of genes express differently under different experimental conditions. Shortcomings of the Fisher's exact test for the overrepresentation analysis are illustrated by an example. Most alternative GSA methods are developed for data collected from two experimental conditions, and most is based on a univariate gene-by-gene test statistic or assume independence among genes in the gene set. A multivariate analysis of variance (MANOVA) approach is proposed for studies with two or more experimental conditions., Results: When the number of genes in the gene set is greater than the number of samples, the sample covariance matrix is singular and ill-condition. The use of standard multivariate methods can result in biases in the analysis. The proposed MANOVA test uses a shrinkage covariance matrix estimator for the sample covariance matrix. The MANOVA test and six other GSA published methods, principal component analysis, SAM-GS, analysis of covariance, Global, GSEA and MaxMean, are evaluated using simulation. The MANOVA test appears to perform the best in terms of control of type I error and power under the models considered in the simulation. Several publicly available microarray datasets under two and three experimental conditions are analyzed for illustrations of GSA. Most methods, except for GSEA and MaxMean, generally are comparable in terms of power of identification of significant gene sets., Availability: A free R-code to perform MANOVA test is available at http://mail.cmu.edu.tw/~catsai/research.htm., Supplementary Information: Supplementary data are available at Bioinformatics online.

Background and Purpose: Influenza is an important cause of acute respiratory illness among military recruits, and pneumonia is the most frequent complication. This study was performed to categorize the clinical manifestations of influenza infections among military recruits., Methods: In this retrospective chart review, epidemiologic investigation of patients who met the definitions of acute respiratory illness, influenza-like illness, and pneumonia was conducted. Surveillance of influenza by viral culture and polymerase chain reaction was performed weekly from a random selection of 4 patients with influenza-like illness of less than 3 days duration., Results: 2074 and 2046 men recruited to the Substitute Service Training Center in Taiwan, from November 30 to December 31, 2006 (outbreak 1), and January 11 to February 12, 2007 (outbreak 2), respectively were enrolled. During outbreak 2, 1182 men (57.7%) were identified to have acute respiratory illness, including 607 (29.6%) with influenza-like illness and 19 (0.9%) with pneumonia. During outbreaks 1 and 2, sixty two nasal and throat swabs were obtained, 15 of which were influenza A and 6 were influenza B. All the influenza A isolates were A/Wisconsin/67(H3N2) viruses. Haemophilus influenzae was isolated from 9 of 19 patients with pneumonia (47.3%); 8 from sputum specimens and 1 from a blood specimen. H. influenzae was the primary identifiable bacterium., Conclusions: The 2 outbreaks consisted of concurrent infection of influenza A and B, with subsequent pneumonia. These results have implications for outbreak management and treatment of influenza among military recruits. Surveillance of influenza-like illness enables early detection of an outbreak and better understanding of the epidemiology of influenza in this setting.