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Abstract Background Network meta-analysis is developed to compare all available treatments; therefore it enriches evidence for clinical decision-making, offering insights into treatment effectiveness and safety when faced with multiple options. However, the complexity and numerous treatment comparisons in network meta-analysis can challenge healthcare providers and patients. The purpose of this study aimed to introduce a graphic design to present complex rankings of multiple interventions comprehensively. Methods Our team members developed a “beading plot” to summary probability of achieving the best treatment (P-best) and global metrics including surface under the cumulative ranking curve (SUCRA) and P-score. Implemented via the “rankinma” R package, this tool summarizes rankings across diverse outcomes in network meta-analyses, and the package received an official release on the Comprehensive R Archive Network (CRAN). It includes the `PlotBead()` function for generating beading plots, which represent treatment rankings among various outcomes. Results Beading plot has been designed based on number line plot, which effectively displays collective metrics for each treatment across various outcomes. Order on the -axis is derived from ranking metrics like P-best, SUCRA, and P-score. Continuous lines represent outcomes, and color-coded beads signify treatments. Conclusion The beading plot is a valuable graphic that intuitively displays treatment rankings across diverse outcomes, enhancing reader-friendliness and aiding decision-making in complex network evidence scenarios. While empowering clinicians and patients to identify optimal treatments, it should be used cautiously, alongside an assessment of the overall evidence certainty.

Isoniazid is an early bactericidal anti-tuberculosis (TB) agent and isoniazid mono-resistance TB is the most prevalent drug-resistant TB worldwide. Concerns exist regarding whether resistance to isoniazid would lead to delayed culture conversion and worst outcomes. From January 2008 to November 2017, adult culture-positive pulmonary TB patients receiving isoniazid, rifampicin, pyrazinamide, and ethambutol were identified through Taiwan Center for Disease Control database and were followed until the end of 2017. Primary outcomes included time to sputum culture conversion (SCC) within two months. Secondary outcomes included death and unfavourable outcomes at the end of 2nd month. A total of 37,193 drug-susceptible and 2,832 isoniazid monoresistant pulmonary TB patients were identified. Compared with no resistance, isoniazid monoresistance was not associated with a delayed SCC (HR: 0.99, 95% CI: 0.94─1.05, p = 0.8145), a higher risk of 2-month mortality (HR: 1.19, 95% CI: 0.92─1.53, p = 0.1884), and unfavourable outcomes at 2nd month (OR: 1.05, 95% CI: 0.97─1.14, p = 0.2427). Isoniazid monoresistance was associated with delayed SCC (HR: 0.90, 95% CI: 0.83─0.98, p = 0.0099) and a higher risk of unfavourable outcomes (OR:1.18, 95% CI: 1.05─1.32, p = 0.0053) in patients aged between 20 and 65, and delayed SCC in patients without underlying comorbidities (HR: 0.90, 95% CI: 0.81─0.98, p = 0.0237). Isoniazid mono-resistant TB had a comparable outcome with drug-susceptible TB at the end of the intensive phase. Healthy, and non-elderly patients were more likely to had culture persistence, raising concerns about disease transmission in these subgroups and warranting early molecular testing for isoniazid resistance.

Abstract Objective To compare the fluid resuscitation effect of sodium acetate Ringer’s solution and sodium bicarbonate Ringer’s solution on patients with traumatic haemorrhagic shock. Method We conducted a prospective cohort study in our emergency department on a total of 71 patients with traumatic haemorrhagic shock admitted between 1 December 2020 and 28 February 2022. Based on the time of admission, patients were randomly divided into a sodium bicarbonate Ringer’s solution group and sodium acetate Ringer’s solution group, and a limited rehydration resuscitation strategy was adopted in both groups. General data were collected separately, and the patients’ vital signs (body temperature, respiration, blood pressure and mean arterial pressure (MAP)), blood gas indices (pH, calculated bicarbonate (cHCO3 −), partial pressure of oxygen (PaO2), partial pressure of carbon dioxide (pCO2) and clearance of lactate (CLac)), shock indices, peripheral platelet counts, prothrombin times and plasma fibrinogen levels were measured and compared before and 1 h after resuscitation. Results The post-resuscitation heart rate of the sodium bicarbonate Ringer’s solution group was significantly lower than that of the sodium acetate Ringer’s solution group (p

Introduction: Few real-world studies have investigated drug-drug interactions (DDIs) involving non-vitamin-K antagonist oral anticoagulants (NOACs) in patients with nonvalvular atrial fibrillation (NVAF). The interactions encompass drugs inducing or inhibiting cytochrome P450 3A4 and permeability glycoprotein. These agents potentially modulate the breakdown and elimination of NOACs. This study investigated the impact of DDIs on thromboembolism in this clinical scenario. Method: Patients who had NVAF and were treated with NOACs were selected as the study cohort from the National Health Insurance Research Database of Taiwan. Cases were defined as patients hospitalised for a thromboembolic event and who underwent a relevant imaging study within 7 days before hospitalisa-tion or during hospitalisation. Each case was matched with up to 4 controls by using the incidence density sampling method. The concurrent use of a cytochrome P450 3A4/permeability glycoprotein inducer or inhibitor or both with NOACs was identified. The effects of these interactions on the risk of thromboembolic events were examined with univariate and multivariate conditional logistic regressions. Results: The study cohort comprised 60,726 eligible patients. Among them, 1288 patients with a thromboembolic event and 5144 matched control patients were selected for analysis. The concurrent use of a cytochrome P450 3A4/permeability glycoprotein inducer resulted in a higher risk of thromboembolic events (adjusted odds ratio [AOR] 1.23, 95% confidence interval [CI] 1.004–1.51). Conclusion: For patients with NVAF receiving NOACs, the concurrent use of cytochrome P450 3A4/ permeability glycoprotein inducers increases the risk of thromboembolic events.

Abstract Background Radiotherapy (RT) is an effective and available local treatment for patients with refractory or relapsed (R/R) aggressive B-cell lymphomas. However, the value of hypofractionated RT in this setting has not been confirmed. Methods We retrospectively analyzed patients with R/R aggressive B-cell lymphoma who received hypofractionated RT between January 2020 and August 2022 at a single institution. The objective response rate (ORR), overall survival (OS), progression-free survival (PFS) and acute side effects were analyzed. Results A total of 30 patients were included. The median dose for residual disease was 36 Gy, at a dose per fraction of 2.3–5 Gy. After RT, the ORR and complete response (CR) rates were 90% and 80%, respectively. With a median follow-up of 10 months (range, 2–27 months), 10 patients (33.3%) experienced disease progression and three died. The 1-year OS and PFS rates for all patients were 81.8% and 66.3%, respectively. The majority (8/10) of post-RT progressions involved out-of-field relapses. Patients with relapsed diseases, no response to systemic therapy, multiple lesions at the time of RT, and no response to RT were associated with out-of-field relapses. PFS was associated with response to RT (P = 0.001) and numbers of residual sites (P

Background: Fluoroquinolones, crucial components of treatment regimens for drug-resistant tuberculosis (TB), are associated with QT interval prolongation and risks of fatal cardiac arrhythmias. However, few studies have explored dynamic changes in the QT interval in patients receiving QT-prolonging agents. Methods: This prospective cohort study recruited hospitalized patients with TB who received fluoroquinolones. The study investigated the variability of the QT interval by using serial electrocardiograms (ECGs) recorded four times daily. This study analyzed the accuracy of intermittent and single-lead ECG monitoring in detecting QT interval prolongation. Results: This study included 32 patients. The mean age was 68.6 ± 13.2 years. The results revealed mild-to-moderate and severe QT interval prolongation in 13 (41%) and 5 (16%) patients, respectively. The incremental yields in sensitivity of one to four daily ECG recordings were 61.0%, 26.1%, 5.6%, and 7.3% in detecting mild-to-moderate QT interval prolongation, and 66.7%, 20.0%, 6.7%, and 6.7% in detecting severe QT interval prolongation. The sensitivity levels of lead II and V5 ECGs in detecting mild-to-moderate and severe QT interval prolongation exceeded 80%, and their specificity levels exceeded 95%. Conclusion: This study revealed a high prevalence of QT interval prolongation in older patients with TB who receive fluoroquinolones, particularly those with multiple cardiovascular risk factors. Sparsely intermittent ECG monitoring, the prevailing strategy in active drug safety monitoring programs, is inadequate owing to multifactorial and circadian QT interval variability. Additional studies performing serial ECG monitoring are warranted to enhance the understanding of dynamic QT interval changes in patients receiving QT-prolonging anti-TB agents.

Background and aim: Acupuncture has been criticized as a theatrical placebo for the sham effect. Unfortunately, sham tests used in control groups in acupuncture studies have always ignored the underlying biophysical factors, including resonance involved in acupuncture points and meridians. Experimental procedure: In this study, the effects of sham acupuncture at Tsu San Li (St-36) were examined by analyzing noninvasive 30-sec. recordings of the radial arterial pulses for 3 groups of patients treated with different probes (blunt, sharp, and patch) on the superficial skin of the acupuncture point. The 3 groups were then treated with the sharp probe for 3 different periods (16, 30, and 50 s). Then we compared the harmonics of the radial arterial pulse after Fourier transformation before and after the treatment. Results: Our results indicated that different probes have effects similar to needle insertion at Tsu San Li. Meanwhile, the harmonic effect of the sharp probe strengthened as time increased. Conclusions: This study revealed that the meridian effect of sham testing from mechanical stimulation, even from simple touch, on an acupuncture point, should not be overlooked. Thus, even simple touch can be added to electrical or laser acupuncture.

Background: Iatrogenic blood loss is an important cause of neonatal anemia. In this study, a spreadsheet tool was developed to reduce blood collection, providing a new idea for the prevention of iatrogenic blood loss in newborns. Methods: Based on hematocrit, minimum test volume and dead volume, a new tool was to calculate the minimum blood collection volume and the number of containers required for the test portfolio. We collected data from October 2022 to October 2023 from Xiamen Maternal and Child Health Hospital for analysis and validation. Results: During this year, there were 16,434 patients and 13,696 plasma/serological samples in the neonatology department. Among them, there were 8 test combinations of greater than 1%, and 9490 samples in total. According to the hospital manual, the recommended amount of blood collection is 27,534 ml and 9490 containers. Through the analysis of this tool, total blood collection was 8864.77 ml, marked qnantity of upward containers (closest level to the calculated blood collection volume) was 10301 ml, and the amount of containers was 8835, which decreased by 67.8%, 62.58% and 6.9% respectively. Besides, if the hematocrit information cannot be obtained in advance and the high hematocrit is calculated as 0.8, the recommended amount of blood collection is 14334.3 ml, and the marked amount of the upward container markering is 17340 ml, decreasing by 47.9% and 37.02% respectively. Conclusion: We have developed an auxiliary tool that can manage neonatal blood specimen collection in a fine and personalized way and can be applied among different laboratory instruments by parameters modification.

T helper (Th) cells are central members of adaptive immunity and comprise the last line of defense against pathogen infection and malignant cell invasion by secreting specific cytokines. These cytokines then attract or induce the activation and differentiation of other immune cells, including antibody-producing B cells and cytotoxic CD8+ T cells. Therefore, the bidirectional communication between Th cells and tumor cells and their positioning within the tumor microenvironment (TME), especially the tumor immune microenvironment (TIME), sculpt the tumor immune landscape, which affects disease initiation and progression. The type, number, and condition of Th cells in the TME and TIME strongly affect tumor immunity, which is precisely regulated by key effectors, such as granzymes, perforins, cytokines, and chemokines. Moreover, microRNAs (miRNAs) have emerged as important regulators of Th cells. In this review, we discuss the role of miRNAs in regulating Th cell mediated adaptive immunity, focusing on the development, activation, fate decisions, and tumor immunity.

Background Research on the cardiovascular toxicity of angiogenesis inhibitors among patients with cancer in Taiwan is lacking. This observational study explored the risk of major adverse cardiovascular events (MACEs) associated with angiogenesis inhibitors in Taiwan. Methods and Results We conducted a nested case‐control study using the TCR (Taiwan Cancer Registry) linked with the Taiwan National Insurance Claim Database. We matched every case with 4 controls using risk‐set sampling by index date, age, sex, cancer type, and cancer diagnosis date. Conditional logistic regression was used to evaluate the risks of MACEs and different cardiovascular events using propensity score adjustment or matching. Sensitivity analyses were used to evaluate the risks matched by cancer stages or exposure within 1 year. Among a cohort of 284 292 after the exclusion of prevalent cases, the incidences of MACEs among the overall cohort and those exposed to angiogenesis inhibitors were 22.5 and 32.5 events per 1000 person‐years, respectively. We matched 17 817 cases with 70 740 controls, with a mean age of 74.9 years, and 56.8% of patients were men. After propensity score adjustment, angiogenesis inhibitors were associated with increased risks of MACEs (odds ratio, 4.56; 95% CI, 1.78–11.59). Significantly increased risks were noted for heart failure hospitalization, myocardial infarction, cerebrovascular accident, and venous thromboembolism, but not for new‐onset atrial fibrillation. Similar results were observed after matching by cancer stage or restriction of 1‐year exposure. Conclusions Angiogenesis inhibitors were associated with increased risks of MACEs among patients with various malignancies in Taiwan but were not associated with new‐onset atrial fibrillation.

Two sympatric Surirella species found at the same specific locality in the Wuling Mountains of China are documented with light and scanning electron microscope. Both species are new to science and named S. wufluminensis sp. nov. and S. suiningensis sp. nov. Surirella wufluminensis has large frustules that are either clockwise or counterclockwise twisted when viewed with the light microscope, and possesses distinctive fibulae, mound-like outgrowths on the valve surface throughout, raised longitudinal ridges on both sides of the raphe, and two helictoglossa-like processes at one apex internally. Surirella suiningensis has narrowly ovate valve outline, distinctive fibulae, troughs alternating with crests from pole to pole, and two helictoglossa-like processes at one apex internally. These two species do not produce costae on the valve surface in contrast to many species in Surirella. This study provides a further two examples of the wide range of morphological diversity in the genus Surirella.

ABSTRACT: Objectives: We conducted an updated network meta-analysis to elucidate the best regimen for latent tuberculosis infection (LTBI). Methods: We searched the PubMed, Embase, and Cochrane Library databases on 16 August 2021 to perform an updated network meta-analysis. Only randomised controlled trials on populations with LTBI that reported the efficacy for preventing incident tuberculosis or the completion rates of treatment regimens were included. The Cochrane Collaboration tool was used to assess the risk of bias. We tested for possible global inconsistency with a χ2 test and local inconsistency by calculating inconsistency factors for each comparison in closed loops. The probability of each regimen being at each possible rank was estimated. Comparison-adjusted funnel plots were obtained to assess publication bias, and sensitivity analysis was performed. The major outcomes were the efficacy for preventing incident tuberculosis and the completion rates of treatment regimens. Results: We identified 27 studies that matched our inclusion criteria; the risk of bias was mostly low. Rifampicin for four months (RFMP-4) was the most likely to be effective (probability: 56.3%) and the second most likely treatment to be completed (probability: 22.4%). By applying a multidimensional scaling approach for ranking based on a scatterplot with the surface under the cumulative ranking values for efficacy and completion rates, RFMP-4 was deemed the best choice for treating LTBI. Similar results were demonstrated after sensitivity analysis. Conclusion: This updated network meta-analysis revealed RFMP-4 to be the best choice for treating LTBI, per simultaneous consideration of efficacy and completion rates.

BackgroundCancer-related fatigue (CRF) is the most distressing side effect in cancer patients and affects the survival rate. However, most patients do not report their fatigue level. This study is aimed to develop an objective CRF assessment method based on heart rate variability (HRV).MethodsIn this study, patients with lung cancer who received chemotherapy or target therapy were enrolled. Patients wore wearable devices with photoplethysmography that regularly recorded HRV parameters for seven consecutive days and completed the Brief Fatigue Inventory (BFI) questionnaire. The collected parameters were divided into the active and sleep phase parameters to allow tracking of fatigue variation. Statistical analysis was used to identify correlations between fatigue scores and HRV parameters.FindingsIn this study, 60 patients with lung cancer were enrolled. The HRV parameters including the low-frequency/high-frequency (LF/HF) ratio and the LF/HF disorder ratio in the active phase and the sleep phase were extracted. A linear classifier with HRV-based cutoff points achieved correct classification rates of 73 and 88% for mild and moderate fatigue levels, respectively.ConclusionFatigue was effectively identified, and the data were effectively classified using a 24-h HRV device. This objective fatigue monitoring method may enable clinicians to effectively handle fatigue problems.

An effective early diagnosis is important for rheumatoid arthritis (RA) management. This study reveals a novel RA detection method using bacteriorhodopsin as a photoelectric transducer, a light-driven proton pump in purple membranes (PMs). It was devised by covalently conjugating a PM monolayer-coated electrode with a citrullinated-inter-alpha-trypsin inhibitor heavy chain 3 (ITIH3)542–556 peptide that recognizes the serum RA-associated autoantibodies. The direct serum coating decreased the photocurrents in the biosensor, with the reduction in the photocurrent caused by coating with an RA-patient serum that is significantly larger than that with a healthy-control serum (38.1% vs. 20.2%). The difference in the reduction in the photocurrent between those two serum groups widened after the serum-coated biosensor was further labeled with gold nanoparticle (AuNP)-conjugated anti-IgA (anti-IgA-AuNP) (53.6% vs. 30.6%). Both atomic force microscopic (AFM) and Raman analyses confirmed the sequential peptide, serum, and anti-IgA-AuNP coatings on the PM-coated substrates. The reductions in the photocurrent measured in both the serum and anti-IgA-AuNPs coating steps correlated well with the results using commercial enzyme-linked immunosorbent assay kits (Spearman rho = 0.805 and 0.787, respectively), with both a sensitivity and specificity close to 100% in both steps. It was shown that an RA diagnosis can be performed in either a single- or two-step mode using the developed biosensor.

Abstract As a model independent approach to search for the signals of new physics (NP) beyond the Standard Model (SM), the SM effective field theory (SMEFT) draws a lot of attention recently. The energy scale of a process is an important parameter in the study of an EFT such as the SMEFT. However, for the processes at a hadron collider with neutrinos in the final states, the energy scales are difficult to reconstruct. In this paper, we study the energy scale of anomalous γγ → W + W − scattering in the vector boson scattering (VBS) process pp → jjℓ + ℓ − ν ν ¯ $$ \overline{\nu} $$ at the large hadron collider (LHC) using artificial neural networks (ANNs). We find that the ANN is a powerful tool to reconstruct the energy scale of γγ → W + W − scattering. The factors affecting the effects of ANNs are also studied. In addition, we make an attempt to interpret the ANN and arrive at an approximate formula which has only five fitting parameters and works much better than the approximation derived from kinematic analysis. With the help of ANN approach, the unitarity bound is applied as a cut on the energy scale of γγ → W + W − scattering, which is found to has a significant suppressive effect on signal events. The sensitivity of the process pp → jjℓ + ℓ − ν ν ¯ $$ \overline{\nu} $$ to anomalous γγWW couplings and the expected constraints on the coefficients at current and possible future LHC are also studied.

BackgroundInterferon in combination with ribavirin has been the standard of care for chronic hepatitis C virus infection (HCV) for the past few decades. However, its effect on the risk of autoimmune diseases (ADs) among patients with HCV infection remains unclear. We assessed the potential association between interferon-based therapy (IBT) and AD risk in patients with HCV infection.MethodsThis retrospective cohort study identified patients diagnosed with HCV infection between January 1, 2006, and December 31, 2015, from Taiwan’s National Health Insurance Research Database. In total, 16,029 patients with HCV infection who received IBT and 141,214 patients with HCV infection who did not receive IBT were included. Both cohorts were followed up to assess the development of ADs. Hazard ratios (HRs) were calculated using the Cox proportional hazards regression model, which was adjusted for potential confounders.ResultsThe median follow-up period for IBT and non-IBT users was 4.53 and 3.34 years, respectively. No significant difference in the risk of overall ADs (adjusted HR [aHR]: 0.96, 95% confidence interval [CI]: 0.81–1.14) or systemic ADs (aHR: 0.88, 95% CI: 0.71–1.10) was noted during the study period. However, a slight increase in the risk of organ-specific ADs was noted among IBT users (incidence rate ratio: 1.33, 95% CI: 1.02–1.72). Furthermore, analysis of AD subgroups revealed a significant increase in the risks of Graves’ disease (aHR: 6.06, 95% CI: 1.27–28.8) and Hashimoto’s thyroiditis (aHR 1.49, 95% CI 1.01–2.21) among IBT users.ConclusionsIBT use increases the risk of autoimmune thyroid diseases (Hashimoto’s thyroiditis and Graves’ disease) in patients with HCV infection to a greater extent than non-IBT use.

Background: Global pandemic resulted from the coronavirus disease-19 (COVID-19) demands mental health concerns on the affected population. We examine the time-course shift of psychological burden among suspected and confirmed COVID-19 patients. Methods: Participants with suspected or confirmed COVID-19 were included in the cohort. Consecutive surveys were conducted upon hospital admission, discharge, and during outpatient follow-up by adapting the 5-item brief symptom rating scale (BSRS-5) assessing psychological symptoms including anxiety, depression, hostility, interpersonal sensitivity, and insomnia. The sixth measure to observe suicidal ideation was also included. Results: A total of 109 eligible patients participated in the study, in which 83.49% reported no distress upon hospital admission, while 2.75%, 3.66%, and 10.1% patients were assessed as being with severe, moderate and mild psychological distress, respectively. Overall, age, sex, and history of contact did not significantly differ between patients with and without psychological distress. Multivariate logistic regression revealed that patients admitted during April–May (OR: 7.66, 95% CI: 1.46–40.28) and presented with symptoms including sore throat (OR: 4.24, 95% CI: 1.17–15.29) and malaise (OR: 5.24, 95% CI: 1.21–22.77) showed significantly higher risk of psychological distress. Cough symptom interestingly showed lower risk of emotional distress (OR: 0.25, 95% CI: 0.08–0.81). Subsequent surveys upon hospital discharge and during outpatient follow-up revealed steadily declining distress among all cohort. Conclusion: At least 16.5% of our cohort reported psychological distress upon hospital admission, with distinct time-dependent decline. Access to mental health support, alongside with promoting positive activities for good mental health are pivotal for those directly affected.

Abstract Background Rheumatoid arthritis (RA) is an autoimmune disorder with systemic inflammation and may be induced by oxidative stress that affects an inflamed joint. Our objectives were to examine isotypes of autoantibodies against 4-hydroxy-2-nonenal (HNE) modifications in RA and associate them with increased levels of autoantibodies in RA patients. Methods Serum samples from 155 female patients [60 with RA, 35 with osteoarthritis (OA), and 60 healthy controls (HCs)] were obtained. Four novel differential HNE-modified peptide adducts, complement factor H (CFAH)1211–1230, haptoglobin (HPT)78–108, immunoglobulin (Ig) kappa chain C region (IGKC)2–19, and prothrombin (THRB)328–345, were re-analyzed using tandem mass spectrometric (MS/MS) spectra (ProteomeXchange: PXD004546) from RA patients vs. HCs. Further, we determined serum protein levels of CFAH, HPT, IGKC and THRB, HNE-protein adducts, and autoantibodies against unmodified and HNE-modified peptides. Significant correlations and odds ratios (ORs) were calculated. Results Levels of HPT in RA patients were greatly higher than the levels in HCs. Levels of HNE-protein adducts and autoantibodies in RA patients were significantly greater than those of HCs. IgM anti-HPT78−108 HNE, IgM anti-IGKC2−19, and IgM anti-IGKC2−19 HNE may be considered as diagnostic biomarkers for RA. Importantly, elevated levels of IgM anti-HPT78−108 HNE, IgM anti-IGKC2−19, and IgG anti-THRB328−345 were positively correlated with the disease activity score in 28 joints for C-reactive protein (DAS28-CRP). Further, the ORs of RA development through IgM anti-HPT78−108 HNE (OR 5.235, p

Abstract The risk of bisphosphonate-related osteonecrosis of the jaw (BRONJ) in primary Sjogren syndrome (pSS) has rarely been explored. To explore the association between BRONJ and pSS, we conducted a population-based propensity-score-matched cohort study using Taiwan’s National Health Insurance Research Database, including pSS patients receiving antiosteoporotic therapy and patients without pSS receiving antiosteoporotic therapy. A 1:4 matched-pair cohort based on propensity score was created. The stratified Cox proportional hazards model compared the risk of BRONJ in the pSS and non-pSS groups. In the study, 23,280 pSS patients and 28,712,152 controls were enrolled. After matching, 348 patients with pSS receiving antiosteoporotic drugs and 50,145 without pSS receiving antiosteoporotic drugs were included for analysis. The risk of developing BRONJ was 1.96 times higher in pSS patients compared with non-pSS patients after adjustment for age, sex, and comorbidities. No dose–response effect was observed in the bisphosphonate-treated pSS cohorts, documented as the cumulative defined daily doses of either

Abstract Objectives The data concerning the association between Tx and ADs remain unclear and are scarce. This study was undertaken to investigate whether people with Tx are more likely to develop ADs, compared to those without Tx. Methods Individuals who received Tx between 2002 and 2015 were identified and matched on age and sex with individuals without Tx. We performed multivariate and stratified analysis using the Kaplan–Meier method and Cox proportional hazards models in order to estimate the association between Tx and the risk of developing ADs. Results A total of 2550 thymectomized (Txd) patients and 24,664.941 non‐Txd comparison subjects were selected from NHIRD. Tx‐MG (myasthenia gravis) as compared with general population (nonTx‐nonMG), adjusted hazard ratio (aHR) were higher for incident Addison disease (aHR = 10.40, 95% CI 1.01–107), autoimmune hemolytic anemia (aHR = 21.54, 95% CI 2.06–14.8), Hashmoto thyroiditis (aHR = 5.52, 95% CI 1.34–34.7), ankylosing spondylitis (aHR = 2.73, 95% CI 1.09–6.84), rheumatoid arthritis (aHR = 5.25, 95% CI 1.79–15.47), primary Sjogren syndrome (pSS) (aHR = 3.77, 95% CI 1.30–11.0), and systemic lupus erythemtoasus (aHR = 10.40). Tx‐nonMG as compared with general population, aHR were higher for incident autoimmune hemolytic anemia (aHR = 25.50), Hashmoto thyroiditis (aHR = 6.75) and systemic lupus erythematosus (SLE) (aHR = 13.38). NonTx‐MG as compared with general population, aHR were higher for incident Hashmoto thyroiditis (aHR = 6.57), pSS (aHR = 4.50), SLE (aHR = 17.29), and systemic vasculitis (aHR = 25.86). Interpretation In conclusion, based on a retrospective cohort study throughout Taiwan, patients with Tx have a higher risk of new onset ADs than patients without Tx.

Objective. The aim of the study is to evaluate the therapeutic effect of hyperbaric oxygen in the treatment of grade III exposed dog bite wounds. Method. Fifty-two patients with grade III dog bite wounds who were seen in the emergency department of our hospital from 2017 to 2021 were selected for this research. The participants were randomly divided into an experimental group and a control group, with 26 patients in each group. The experimental group received hyperbaric oxygen therapy (HBOT), and the control group received routine treatment. The patients were followed up for three months after the treatment concluded. The wound healing rate, infection rate, and healing time were measured and compared. Results. The cure rate of the experimental group (96.2%) was higher than that of the control group (69.2%). The infection rate in the experimental group (3.8%) was lower than that of the control group (30.8%). The average cure time of the experimental group (9 ± 2.7) was lower than that of the control group (11 ± 3.4). The number of dressing changes in the experimental group (4 ± 3.0) was lower than that of the control group (7.5 ± 3.5), and there was a significant difference between the two groups (P

Introduction. Postoperative delirium can increase cognitive impairment and mortality in patients with Parkinson’s disease. The purpose of this study was to develop and internally validate a clinical prediction model of delirium after deep brain stimulation of the subthalamic nucleus in Parkinson’s disease under general anesthesia. Methods. We conducted a retrospective observational cohort study on the data of 240 patients with Parkinson’s disease who underwent deep brain stimulation of the subthalamic nucleus under general anesthesia. Demographic characteristics, clinical evaluation, imaging data, laboratory data, and surgical anesthesia information were collected. Multivariate logistic regression was used to develop the prediction model for postoperative delirium. Results. A total of 159 patients were included in the cohort, of which 38 (23.90%) had postoperative delirium. Smoking (OR 4.51, 95% CI 1.56–13.02, p

BackgroundPrevious study revealed proton pump inhibitors (PPIs) have an effect on gut microbiota. Alteration of the microbiome causes changes of the host immune system and then induces the development of autoimmune diseases (ADs). This study aimed to explore the possible association between PPIs use and ADs.MethodsThis study was conducted using data from the Taiwan National Health Insurance Research Database in the period between 2002 and 2015. We performed multivariate and stratified analysis through the Kaplan-Meier method and Cox proportional hazard models to estimate the association between proton pump inhibitor use and the risk of autoimmune diseases.ResultsOf the 297,099 patients treated with PPI identified, the overall mean (SD) age was 49.17 (15.63) years and 56.28% of the subjects was male. As compared with the non-PPI group, the adjusted hazard ratio (aHR) were higher for incident organ specific ADs such as Graves disease (aHR=3.28), Hashmoto thyroiditis (aHR=3.61), autoimmune hemolytic anemia (aHR=8.88), immune thrombocytopenic purpura (aHR=5.05) Henoch-Schonlein pupura (aHR=4.83) and Myasthenia gravis (aHR=8.73). Furthermore, the adjusted hazard ratio (aHR) were also higher for incident systemic ADs such as ankylosing spondylitis (aHR=3.67), rheumatoid arthritis (aHR=3.96), primary Sjogren syndrome (aHR=7.81), systemic lupus erythemtoasus (aHR=7.03). systemic vasculitis (aHR=5.10), psoriasis (aHR=2.57), systemic scleroderma (aHR=15.85) and inflammatory myopathy (aHR=37.40). Furthermore, we observed no dose-dependent effect between PPI use and the risk of ADs.ConclusionsOur retrospective population-based cohort study showed that the prescription of proton pump inhibitors is associated with a higher risk of ADs.

Abstract Human height can be described as a classical and inherited trait model. Genome-wide association studies (GWAS) have revealed susceptible loci and provided insights into the polygenic nature of human height. Familial short stature (FSS) represents a suitable trait for investigating short stature genetics because disease associations with short stature have been ruled out in this case. In addition, FSS is caused only by genetically inherited factors. In this study, we explored the correlations of FSS risk with the genetic loci associated with human height in previous GWAS, alone and cumulatively. We systematically evaluated 34 known human height single nucleotide polymorphisms (SNPs) in relation to FSS in the additive model (p

Elevated Renal cell carcinoma (RCC) risk has been associated with the use of several antihypertensive medications but has not yet been elucidated in the populations prescribed alpha-1 blockers that are commonly used in the treatment of hypertension and lower urinary tract symptoms associated with benign prostatic hyperplasia (LUTS-BPH). The aim of the present study was to investigate the association between alpha-1 blocker use and the risk of developing RCC using a nationwide population-based database in Taiwan. Patients who were treated with alpha-1 blockers for at least 28 days were identified through the Taiwan National Health Insurance Research Database from 2000 to 2010. The unexposed participants were matched with the exposed cases according to age, sex, and index year at a ratio of 3:1. Cox proportional hazards regression, stratified by sex and comorbidities and adjusted for age, was performed to estimate hazard ratios (HRs) for the risk of subsequent RCC. Among 2,232,092 subjects, patients who received alpha-1 blocker treatment had a higher risk of RCC than the unexposed group. Taking into account hypertension and BPH, the adjusted HR was significantly higher in male alpha-1 blocker users who had no BPH and either the presence (HR: 1.63, 95% confidence interval [CI] = 1.22-2.18) or absence (HR: 2.31, 95% CI = 1.40-3.81) of hypertension than in men not receiving these drugs. Taken together, male alpha-1 blocker users who had no comorbidity of BPH exhibited an increased risk for developing RCC independent of hypertension. Further study is warranted to elucidate the underlying mechanisms of this association.

Machine learning (ML) algorithms have been applied to predicting coronary artery disease (CAD). Our purpose was to utilize autoantibody isotypes against four different unmodified and malondialdehyde (MDA)-modified peptides among Taiwanese with CAD and healthy controls (HCs) for CAD prediction. In this study, levels of MDA, MDA-modified protein (MDA-protein) adducts, and autoantibody isotypes against unmodified peptides and MDA-modified peptides were measured with enzyme-linked immunosorbent assay (ELISA). To improve the performance of ML, we used decision tree (DT), random forest (RF), and support vector machine (SVM) coupled with five-fold cross validation and parameters optimization. Levels of plasma MDA and MDA-protein adducts were higher in CAD patients than in HCs. IgM anti-IGKC76–99 MDA and IgM anti-A1AT284–298 MDA decreased the most in patients with CAD compared to HCs. In the experimental results of CAD prediction, the decision tree classifier achieved an area under the curve (AUC) of 0.81; the random forest classifier achieved an AUC of 0.94; the support vector machine achieved an AUC of 0.65 for differentiating between CAD patients with stenosis rates of 70% and HCs. In this study, we demonstrated that autoantibody isotypes imported into machine learning algorithms can lead to accurate models for clinical use.

Using data from approximately 342,000 course-taking records collected from 4406 college students enrolled at Taipei Tech during the 2009-2012 academic years, we examine the impact of multidisciplinarity on students' academic performance. Our study contributes to the literature in three ways. First, by applying natural language processing (NLP), we analyze course descriptions of 375 subject areas from the Classification of Instructional Programs and measure the pairwise distances among them. Second, based on the course-taking records and the subject area distribution, we measure each student's degree of multidisciplinary learning using a proposed weighted entropy formula. Third, using the proposed multidisciplinary index, we find that the impact of multidisciplinary course-taking experience on individual students' academic performance varies across academic fields. In the college of engineering, the college of electrical engineering and computer science, and the college of mechanical and electrical engineering, a higher level of multidisciplinarity is associated with a higher average weighted GPA in core courses. However, a positive association does not exist for students in the college of management.

The administration of A/B exams usually involves the use of items. Issues arise when the pre-establishment of a question bank is necessary and the inconsistency in the knowledge points to be tested (in the two exams) reduces the exams ‘fairness’. These are critical for a large multi-teacher course wherein the teachers are changed such that the course and examination content are altered every few years. However, a fair test with randomly participating students should still be a guaranteed subject with no item pool. Through data-driven decision-making, this study collected data related to a term test for a compulsory general course for empirical assessments, pre-processed the data and used item response theory to statistically estimate the difficulty, discrimination and lower asymptotic for each item in the two exam papers. Binary goal programing was finally used to analyze and balance the fairness of A/B exams without an item pool. As a result, pairs of associated questions in the two exam papers were optimized in terms of their overall balance in three dimensions (as the goals) through the paired exchanges of items. These exam papers guarantee their consistency (in the tested knowledge points) and also ensure the fairness of the term test (a key psychological factor that motivates continued studies). Such an application is novel as the teacher(s) did not have a pre-set question bank and could formulate the fairest strategy for the A/B exam papers. The model can be employed to address similar teaching practice issues.

BackgroundThe evidence supporting the benefit of femoral nerve block (FNB) for positioning before spinal anesthesia (SA) in patients suffering from a femur fracture remains inconclusive. In the present study, the authors intended to determine the efficacy and safety of FNB versus an intravenous analgesic (IVA) for positioning before SA in patients with a femur fracture.MethodPubMed, EMBASE, Cochrane, and Scopus databases were searched up to January 2018. We included randomized controlled studies (RCTs) and observational studies that compared FNB versus IVA for the positioning of patients with femur fracture receiving SA. The primary outcome was pain scores during positioning within 30 min before SA. Secondary outcomes were the time for SA, additional analgesic requirements, anesthesiologist's satisfaction with the quality of positioning for SA, participant acceptance, and hemodynamic changes. A random-effects model was used to synthesize the data. We registered the study at PROSPERO with an ID of CRD42018091450.ResultsTen studies with 584 patients were eligible for inclusion. FNB achieved significantly lower pain scores than IVA during positioning within 30 min before SA (pooled standardized mean deviation (SMD): -1.27, 95% confidence interval (CI): -1.84 to -0.70, p < 0.05). A subgroup analysis showed that the analgesic effect was larger in patients in the sitting position for SA than a non-sitting position (sitting position vs non-sitting: pooled SMD: -1.75 (p < 0.05) vs -0.61 (not significant). A multivariate regression showed that the analgesic effect was also associated with age and the total equivalent amount as lidocaine after adjusting for gender (age: coefficient 0.048, p < 0.05; total equivalent amount as lidocaine: coefficient 0.005, p < 0.05). Patients receiving FNB also had a significantly shorter time for SA, greater anesthesiologist satisfaction, and higher patient acceptance than patients receiving IVA. The use of local anesthetics did not produce significant clinical hemodynamic change.ConclusionCompared to IVA, FNB was an effective and safe strategy for the positioning of femur fracture patients for a spinal block, particularly patients who received SA in the sitting position.

Treatment with direct-acting antivirals (DAAs) cures most patients infected with hepatitis C virus (HCV) in the real world. However, some patients, especially those with the underlying advanced liver disease, have a limited reduction of liver injury after achieving a sustained viral response (SVR). Bicyclol was widely used in clinics for the treatment of a variety of liver injuries but with an unknown mechanism for the treatment of hepatitis C. We investigated the anti-inflammatory effects and mechanisms of bicyclol in HCV-infected hepatocytes and further confirmed the putative results in a mouse hepatitis model induced by the coinjection of polyinosinic-polycytidylic acid [poly (I:C)] and D-galactosamine (D-GalN). The results showed that the activation of nuclear factor kappa B (NF-κB) and the subsequent increase of inflammatory factors were directly induced by HCV infection and were persistent after clearance of the virus in Huh7.5 cells. Bicyclol decreased the activation of NF-κB and the levels of inflammatory factors in HCV-infected hepatocytes by inhibiting the activation of the ROS-MAPK-NF-κB pathway, and the effect was synergistic with DAAs in HCV-infected hepatocytes. Bicyclol attenuated the ROS-MAPK-NF-κB axis via recovering mitochondrial function without a dependence on dihydronicotinamide adenine dinucleotide phosphate oxidase and superoxide dismutases. The anti-inflammatory effects and mechanism of bicyclol were verified in mouse hepatitis induced by the coinjection of poly(I:C)/D-GalN. Bicyclol directly ameliorates the chronic inflammation caused by HCV infection and might be used with DAAs or after DAA therapy for ultimately curing chronic hepatitis C.

Dementia is a common neurological disease that substantially affects public health. A previous study revealed that dementia occurs when the body's immune system attacks the cells of the brain, indicating that dementia may be similar to autoimmune rheumatic diseases (ARDs). In the current retrospective cohort study, we focused on middle-aged ARD patients (45 years or older) to investigate the association between ARDs in middle-aged people and dementia by using a nationwide population-based database in Taiwan.Our study analyzed the medical data of the Taiwanese population from 2001 to 2012, with a follow-up period extending until the end of 2011. We identified middle-aged patients with ARDs by using the Taiwan National Health Insurance Research Database. We selected a comparison cohort from the general population that was randomly frequency-matched by age (in 5-year increments), sex, and index year and further analyzed the dementia risk by using a Cox regression model that considers sex, age, and comorbidities.The study enrolled 34,660 middle-aged ARD patients (77% female, mean age = 59.8 years) and 138,640 controls. The risk of developing dementia was 1.18 times higher for middle-aged patients with ARDs compared with patients without ARDs after adjustment for age, sex, and comorbidities. Among the patients with ARDs, the subgroups with rheumatoid arthritis, systemic lupus erythematosus, and Sjögren syndrome (SS) were associated with a significantly higher dementia risk (adjusted hazard ratio [HR] 1.14, 95% confidence index [CI] 1.06-1.32; adjusted HR 1.07, 95% CI 0.86-1.34; adjusted HR 1.46, 95% CI 1.32-1.63, respectively). Furthermore, primary SS and secondary SS patients had the highest risks of dementia among all the ADR subgroups (adjusted HR 1.35, 95% CI 1.18-1.54; adjusted HR 1.67, 95% CI 1.43-1.95 respectively).This nationwide retrospective cohort study demonstrated that dementia risk is significantly higher in middle-aged patients with ARDs compared with the general population.

The objective of this study was to identify novel acetylation (Ac) modifications of the C1-inhibitor (C1-INH) and explain the association of the levels of autoantibodies against acetylated C1-INH peptides with the risk of developing systemic lupus erythematosus (SLE). Ac modifications of the C1-INH were identified and validated through in-gel digestion, nano-liquid chromatography-tandem mass spectrometry, immunoprecipitation, and Western blotting by using serum protein samples obtained from patients with SLE and age-matched healthy controls (HCs). In addition, the levels of serum C1-INH, Ac-protein adducts, and autoantibodies against unmodified and acetylated C1-INH peptides were measured. C1-INH levels in patients with SLE were significantly lower than those in HCs by 1.53-fold (p = 0.0008); however, Ac-protein adduct concentrations in patients with SLE were significantly higher than those in HCs by 1.35-fold (p = 0.0009). Moreover, immunoglobulin M (IgM) anti-C1-INH367−385 Ac and IgA anti-C1-INH367−385 Ac levels in patients with SLE were significantly lower than those in HCs. The low levels of IgM anti-C1-INH367−385 (odds ratio [OR] = 4.725, p < 0.001), IgM anti-C1-INH367−385 Ac (OR = 4.089, p = 0.001), and IgA anti-C1-INH367−385 Ac (OR = 5.566, p < 0.001) indicated increased risks for the development of SLE compared with HCs.

BACKGROUND:Some oral probiotics have been shown to prevent necrotizing enterocolitis (NEC) and decrease mortality effectively in preterm very low birth weight (PVLBW) infants. However, it is unclear whether a single probiotic or a mixture of probiotics is most effective for the prevention of NEC. OBJECTIVE:A meta-analysis was conducted by reviewing the most up to date literature to investigate whether multiple strains probiotics are more effective than a single strain in reducing NEC and death in PVLBW infants. DATA SOURCES:Relevant studies were identified by searches of the MEDLINE, EMBASE, and Cochrane CENTRAL databases, from 2001 to 2016. DATA EXTRACTION AND SYNTHESIS:The inclusion criteria were randomized controlled trials of any enteral probiotic supplementation that was initiated within the first 7 days and continued for at least 14 days in preterm infants (≤ 34 weeks' gestation) and/or those of a birth weight ≤1500 g. RESULTS:A total of 25 trials (n = 7345 infants) were eligible for inclusion in the meta-analysis using a fixed-effects model. Multiple strains probiotics were associated with a marked reduction in the incidence of NEC, with a pooled OR of 0.36 (95% CI, 0.24-0.53; P < .00001). Single strain probiotic using Lactobacillus species had a borderline effect in reducing NEC (OR of 0.60; 95% CI 0.36-1.0; P = .05), but not mortality. Multiple strains probiotics had a greater effectiveness in reducing mortality and were associated with a pooled OR of 0.58 (95% CI, 0.43-0.79; P = .0006). Trials using single strain of Bifidobacterium species and Saccharomyces boulardii did not reveal any beneficial effects in terms of reducing NEC or mortality. CONCLUSION:This updated report found that multiple strains probiotics appear to be the most feasible and effective strategy for the prevention of NEC and reduction of mortality in PVLBW neonates. Further clinical trials should focus on which probiotic combinations are most effective.

This paper gives a brief description of the over quick urbanization sinceChongqing, one of the biggest cities in China, has been a municipality directly under theCentral Government in 1997, excessive development and exceeding increase of high-risebuildings because of its special geographical position which finally leads to the worseningof the urban outdoor thermal environment. Then, this paper makes a bright balance to thefield measurement and simulated results of the wind speed field, temperature field of onemultifunctional high-rise building in Chongqing university located in the city center, andthe contrasted results validate the correctness of CFD in the outdoor thermal environmentalsimulation, expose the disadvantages of high-rise buildings on the aspects of blocking thewind field, decreasing wind speed which results in accumulation of the air-conditioningheat revolving around and periscian region where sunshine can not rip into. Finally, inorder to improve the urban outdoor thermal environment near the high-rise buildingsespecially for the angle of natural ventilation, this paper simulates the wind environment indifferent architectural compositions and architectural layouts by CFD, and the simulatedresults show that freestyle and tower buildings which can guarantee the wind speed andtake the air-conditioning heat away are much suitable and reasonable for the specialChongqing geography. These conclusions can also be used as a reference in othermountain cities, especially for the one with a great number of populations.

Type 2 diabetes (T2D) is a chronic, multifactorial, and metabolic disorder accounting for 90% diabetes cases worldwide. Among them, almost half of T2D have hypertension, which is responsible for cardiovascular disease, morbidity, and mortality in these patients. The Chinese herbal medicine (CHM) prescription patterns of hypertension individuals among T2D patients have yet to be characterized. This study, therefore, aimed to determine their prescription patterns and evaluate the CHM effect. A cohort of one million randomly sampled cases from the National Health Insurance Research Database (NHIRD) was used to investigate the overall survival rate of CHM users, and prescription patterns. After matching CHM and non-CHM users for age, gender and date of diagnosis of hypertension, 980 subjects for each group were selected. The CHM users were characterized with slightly longer duration time from diabetes to hypertension, and more cases for hyperlipidaemia. The cumulative survival probabilities were higher in CHM users than in non-CHM users. Among these top 12 herbs, Liu-Wei-Di-Huang-Wan, Jia-Wei-Xiao-Yao-San, Dan-Shen, and Ge-Gen were the most common herbs and inhibited in vitro smooth muscle cell contractility. Our study also provides a CHM comprehensive list that may be useful in future investigation of the safety and efficacy for individuals with hypertension among type 2 diabetes patients.

Patients demonstrate notable variations in disease progression following human immunodeficiency virus (HIV) infection. We aimed to identify ZNRD1 and RNF39 genetic variants linked to AIDS progression. We conducted a genetic association study in HIV-1-infected Han Chinese patients residing in Taiwan. The clinical characteristics of 143 HIV-1-infected patients were measured, and patients were split into 2 groups: AIDS progression and AIDS non-progression. Genotyping of ZNRD1 and RNF39 was performed in all participants. We found that patients in the AIDS progression group had higher HIV-1 viral loads and lower CD4 cell counts than did patients in the AIDS non-progression group. The frequency of the AA genotype of ZNRD1 (rs16896970) was lower in the AIDS progression group than in the AIDS non-progression group. Patients with AA genotypes had lower levels of HIV-1 viral loads and higher levels of CD4 cell counts than did patients with AG+GG genotypes. AIDS progression in patients with the AA group is significantly different from that in patients with the AG and GG groups by using Kaplan-Meier survival analysis. The hazard ratio for progression was lower in the AA group than in the AG and GG groups. We identified a SNP that contributes to AIDS progression in HIV-1-infected patients in this population. This SNP had a significant protective influence on AIDS progression, and polymorphisms of the ZNRD1 gene may play a role in the pathogenesis of HIV-1 infection.

Kawasaki disease (KD) is pediatric systemic vasculitis with the classic complication of coronary artery aneurysm (CAA). It is the leading cause of acquired cardiovascular diseases in children. Some severe cases present with multi-organ involvement or neurological dysfunction. To identify the role of the glutamate receptor, ionotropic, N-methyl-d-aspartate 3A (GRIN3A) in KD, we investigated genetic variations in GRIN3A in a Taiwanese cohort of 262 KD patients (76 with and 186 without CAA complications). We used univariate and multivariate regression analyses to identify the associations between clinical characteristics and GRIN3A genetic variations in KD. According to univariate regression analysis, CAA formation in KD was significantly associated with fever duration (p < 0.0001), first Intravenous immunoglobulin (IVIG) used (days after day one of fever) (p < 0.0001), and the GRIN3A (rs7849782) genetic variant (p < 0.001). KD patients with GG+GC genotype showed a lower rate of developing CAA (GG+GC genotype: odds ratio = 0.26; 95% CI = 0.14-0.46). Significant associations were identified between KD with CAA complication and the GRIN3A (rs7849782) genetic variant by using multivariate regression analysis. Specifically, significant correlations were observed between KD with CAA complications and the presence of GG+GC genotypes for the GRIN3A rs7849782 single-nucleotide polymorphism (full model: odds ratio = 0.25; 95% CI = 0.14-0.46). Our results suggest that a polymorphism of the GRIN3A gene may play a role in KD pathogenesis.

Despite the success of genome-wide association studies (GWASs) in detecting common variants (minor allele frequency ≥0.05) many suggested that rare variants also contribute to the genetic architecture of diseases. Recently, researchers demonstrated that rare variants can show a strong stratification which may not be corrected by using existing methods. In this paper, we focus on a case-parents study and consider methods for testing group-wise association between multiple rare (and common) variants in a gene region and a disease. All tests depend on the numbers of transmitted mutant alleles from parents to their diseased children across variants and hence they are robust to the effect of population stratification. We use extensive simulation studies to compare the performance of four competing tests: the largest single-variant transmission disequilibrium test (TDT), multivariable test, combined TDT, and a likelihood ratio test based on a random-effects model. We find that the likelihood ratio test is most powerful in a wide range of settings and there is no negative impact to its power performance when common variants are also included in the analysis. If deleterious and protective variants are simultaneously analyzed, the likelihood ratio test was generally insensitive to the effect directionality, unless the effects are extremely inconsistent in one direction.

BackgroundRelying 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 findingsStarting 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).ConclusionsApproximately 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.

In the title complex, [Pr(C9H4N2O4)(C2H3O2)(H2O)]n, the PrIII ion is coordinated by five O atoms and one N atom from four benzimidazole-5,6-dicarboxylate ligands, two O atoms from an acetate ligand and one water molecule, giving a tricapped trigonal-prismatic geometry. The benzimidazole-5,6-dicarboxylate and acetate ligands connect the PrIII ions, forming a layer in the ac plane; the layers are further linked by N—H...O and O—H...O hydrogen bonding and π–π stacking interactions between neighboring pyridine rings [the centroid–centroid distance is 3.467 (1) Å], assembling a three-dimensional supramolecular network. The acetate methyl group is disordered over two positions with site-occupancy factors of 0.75 and 0.25.

Hierarchical MnO2 microfibers were prepared by using cotton as the template and KMnO4 as the precursor via an ultrasonic assistance route. The results of scanning electron microscope characterization showed that the concentration of KMnO4 had a significant effect on the morphology of MnO2 microfiber. At low concentration of KMnO4, the microfiber was composed of MnO2 nanorods with single crystal structure. With increasing the concentration of KMnO4, the secondary nanostructure of MnO2 microfibers had a transformation from nanorod to nanoparticle. The results of N2 adsorption-desorption analysis indicated that MnO2 microfibers had BET surface area of about 25 m2/g. This synthesis provides a new way to control the secondary nanostructure of MnO2 microfiber by adjusting the concentration of precursor. Furthermore, the mechanism for the replication was proposed and discussed.