Use of simple clinical and laboratory predictors to differentiate influenza from dengue and other febrile illnesses in the emergency room.

BACKGROUND: Clinical differentiation of influenza from dengue and other febrile illnesses (OFI) is difficult, and available rapid diagnostic tests have limited sensitivity. METHODS: We conducted a retrospective study to compare clinical and laboratory findings between (i) influenza and dengue and (ii) influenza and OFI. RESULTS: Of 849 enrolled patients, the mean time between illness onset and hospital presentation was 1.7, 3.7, and 3 days for influenza, dengue, and OFI, respectively. Among pediatric patients (≤18 years) (445 influenza, 24 dengue, and 130 OFI), we identified absence of rashes, no leukopenia, and no marked thrombocytopenia (platelet counts <100 × 10(9) cells/L) as predictors to distinguish influenza from dengue, whereas rhinorrhea, malaise, sore throat, and mild thrombocytopenia (platelet counts 100-149 × 10(9)/L) were predictors that differentiated influenza from OFI. Among adults (>18 years) (81 influenza, 124 dengue, and 45 OFI), no leukopenia and no marked thrombocytopenia distinguished influenza from dengue, while rhinorrhea and malaise differentiated influenza from OFI. A diagnostic algorithm developed to distinguish influenza from dengue using rash, leukopenia, and marked thrombocytopenia showed >90% sensitivity to identify influenza in pediatric patients. CONCLUSIONS: This study identified simple clinical and laboratory parameters that can assist clinicians to distinguish influenza from dengue and OFI. These findings may help clinicians diagnose influenza and facilitate appropriate management of affected patients, particularly in resource-poor settings.

Natural Berberine-derived Azolyl Ethanols as New Structural Antibacterial Agents against Drug-Resistant Escherichia coli.

Natural berberine-derived azolyl ethanols as new structural antibacterial agents were designed and synthesized for fighting with dreadful bacterial resistance. Partial target molecules exhibited potent activity against the tested strains, particularly, nitroimidazole derivative 4d and benzothiazole-2-thoil compound 18b, with low cytotoxicity both exerted strong antibacterial activities against multidrug-resistant Escherichia coli at low concentrations as 0.007 and 0.006 mM, respectively. Meanwhile, the active compounds 4d and 18b possessed the ability to rapidly kill bacteria and observably eradicate the E. coli biofilm by reducing exopolysaccharide content to prevent bacterial adhesion, which was conducive to alleviating the development of E. coli resistance. Preliminary mechanistic explorations suggested that the excellent antibacterial potential of molecules 4d and 18b might be attributed to their ability to disintegrate membrane, accelerate ROS accumulation, reduce bacterial metabolism, and intercalate into DNA groove. These results provided powerful information for the further exploitation of natural berberine derivatives against bacterial pathogens.

Graph Neural Networks for Charged Particle Tracking on FPGAs.

The determination of charged particle trajectories in collisions at the CERN Large Hadron Collider (LHC) is an important but challenging problem, especially in the high interaction density conditions expected during the future high-luminosity phase of the LHC (HL-LHC). Graph neural networks (GNNs) are a type of geometric deep learning algorithm that has successfully been applied to this task by embedding tracker data as a graph-nodes represent hits, while edges represent possible track segments-and classifying the edges as true or fake track segments. However, their study in hardware- or software-based trigger applications has been limited due to their large computational cost. In this paper, we introduce an automated translation workflow, integrated into a broader tool called hls4ml, for converting GNNs into firmware for field-programmable gate arrays (FPGAs). We use this translation tool to implement GNNs for charged particle tracking, trained using the TrackML challenge dataset, on FPGAs with designs targeting different graph sizes, task complexites, and latency/throughput requirements. This work could enable the inclusion of charged particle tracking GNNs at the trigger level for HL-LHC experiments.

Analysis of transcriptome difference between rapid-growing and slow-growing in Penaeus vannamei.

Penaeus vannamei is the principle cultured shrimp species in China. However, with the increase of culture density, the growth difference between individuals is also expanding. Here, we make use of RNA-seq to study the growth mechanisms of P. vannamei. After 120 days, we examined the transcriptomes of rapid-growing individuals (RG) and slow-growing individuals (SG). A total of 2116 and 176 differentially expressed genes (DEGs) were found in SG and RG, respectively. Moreover, the main DEGs are opsin, heat shock protein (HSP), actin, myosin, superoxide dismutase (SOD), cuticle protein, and chitinase. GO analysis further revealed that the DEGs were enriched in biological processes significantly, such as "sensory perception," "sensory perception of light stimulus," "response to stimulus," and "response to stress." Additionally, KEGG enrichment analysis showed that the DEGs were mainly enriched in "pentose and glucuronate interconversions," "amino sugar and nucleotide sugar metabolism," "glycophospholipid biosynthesis," and "glutathione metabolism." Interestingly, the upstream genes in the ecdysone signaling pathway, including molting inhibition hormone (MIH) and crustacean hyperglycemic hormone (CHH), did not differ significantly between RG and SG, which suggests that the cause for the inconsistent growth performance is due to the stress levels rather than the ecdysone signal pathway. In summary, this work provides data that will be useful for future studies on shrimp growth and development.

Massive Pulmonary Embolism Concomitant With Cardiac Tamponade as Initial Presentation of Lung Adenocarcinoma: A Diagnostic and Therapeutic Dilemma.

Pulmonary embolism and cardiac tamponade are potentially fatal acute conditions that rarely present concomitantly in the emergency department (ED). Both require early diagnosis and urgent intervention, and are usually observed as separate easily identifiable diseases. However, in a patient exhibiting a concomitant presentation of pulmonary embolism with cardiac tamponade, diagnosis and therapeutic intervention are extremely challenging. A 48-year-old woman presented with cardiac tamponade as an initial symptom of an underlying lung adenocarcinoma and masked massive pulmonary embolism (MPE), which led to the development of sudden cardiac arrest after successful pericardiocentesis. She presented with a high index of suspicion for a diagnosis of MPE using echocardiography after successful pericardiocentesis, and this diagnosis was confirmed using computed tomography. Extracorporeal membrane oxygenation and adjusted-dose unfractionated intravenous heparin administration were performed; unfortunately, they were unsuccessful. This report would help ED physicians because this case demonstrates that lung cancer can initially present as pulmonary embolism with cardiac tamponade and pulmonary embolism can be misdiagnosed in the presence of concomitant cardiac tamponade. Bedside echocardiography may fail to diagnose life-threatening MPE with coexisting cardiac tamponade. MPE can also lead to the development of sudden cardiac arrest after successful pericardiocentesis. Thrombolytic and anticoagulant use in MPE with coexisting hemorrhagic cardiac tamponade is a controversial issue. The risk-benefit ratio of both therapies needs to be considered on a case-by-case basis for improved clinical outcomes.

Analysis of miRNAs Targeted Storage Regulatory Genes during Soybean Seed Development Based on Transcriptome Sequencing.

Soybeans are an important cash crop and are widely used as a source of vegetable protein and edible oil. MicroRNAs (miRNA) are endogenous small RNA that play an important regulatory role in the evolutionarily conserved system of gene expression. In this study, we selected four lines with extreme phenotypes, as well as high or low protein and oil content, from the chromosome segment substitution line (CSSL) constructed from suinong (SN14) and ZYD00006, and planted and sampled at three stages of grain development for small RNA sequencing and expression analysis. The sequencing results revealed the expression pattern of miRNA in the materials, and predicted miRNA-targeted regulatory genes, including 1967 pairs of corresponding relationships between known-miRNA and their target genes, as well as 597 pairs of corresponding relationships between novel-miRNA and their target genes. After screening and annotating genes that were targeted for regulation, five specific genes were identified to be differentially expressed during seed development and subsequently analyzed for their regulatory relationship with miRNAs. The expression pattern of the targeted gene was verified by Real-time Quantitative PCR (RT-qPCR). Our research provides more information about the miRNA regulatory network in soybeans and further identifies useful genes that regulate storage during soy grain development, providing a theoretical basis for the regulation of soybean quality traits.

[Comparative studies on the characteristics of the Fourier-transform infrared spectra between sturgeon and shark chondroitin sulfates].

The characteristics of the Fourier-transform infrared spectra of sturgeon and shark chondroitin sulfates (CHSs) were comparatively studied. The results show that sturgeon CHS exhibits special vibrations at the wavenumbers of 1 376, 1 344, 1 310, 1 157, 883 and 856 cm(-1). Further analysis shows that shark CHS contains 6-sulfated-CHS, while sturgeon CHS contains 4, 6-disulfated CHS, indicating that sturgeon CHS could have higher biological activities in decreasing the toxicity of medicine and in killing cancer cells. In general, the two kinds of CHSs have similar infrared spectra and groups of acylamino, carboxyl, sulfate, and saccharide ring. But the N-H variable-angle vibration of acylamino group of sturgeon CHS occurs at the higher wavenumber, and the vibration intensity of carboxyl group at 1 415 cm(-1) is also stronger than that of shark CHS. Chemical analysis shows that sturgeon CHS has a higher content of glucuronic acid, suggesting that it probably could be a better kind of medical materials for the bone mineralization.

Lead Poisoning Can Be Easily Misdiagnosed as Acute Porphyria and Nonspecific Abdominal Pain.

Lead poisoning (LP) is less commonly encountered in emergency departments (ED). However, lead exposure still occurs, and new sources of poisoning have emerged. LP often goes unrecognized due to a low index of suspicion and nonspecific symptoms. We present a case of a 48-year-old man who had recurring abdominal pain with anemia that was misdiagnosed. His condition was initially diagnosed as nonspecific abdominal pain and acute porphyria. Acute porphyria-like symptoms with a positive urine porphyrin test result led to the misdiagnosis; testing for heme precursors in urine is the key to the differential diagnosis between LP and acute porphyria. The final definitive diagnosis of lead toxicity was confirmed based on high blood lead levels after detailed medical history taking. The lead poisoning was caused by traditional Chinese herbal pills. The abdominal pain disappeared after a course of chelating treatment. The triad for the diagnosis of lead poisoning should be a history of medicine intake, anemia with basophilic stippling, and recurrent abdominal pain.

Increased Mortality in Seasonal H3N2 Patients Compared with those with Pandemic 2009 H1N1 in Taiwan, 2009-2010.

We conducted a retrospective study to compare clinical and laboratory findings between 1) severe influenza A and mild influenza A and 2) pandemic 2009 H1N1 (pdm09 A/H1) and seasonal H3N2 (A/H3) from 2009 to 2010. A total of 526 (mean age, 13.6 years; 447 pdm09 A/H1, 79 seasonal A/H3) patients were included, 41 (7.8%) with severe influenza (mean age, 28.1 years; 26 pdm09 A/H1, 15 seasonal A/H3). Influenza-associated complications were pneumonia (75.6%), meningoencephalitis (14.6%), acute kidney injury (14.6%), and acute respiratory distress syndrome (12.2%). Patients with seasonal A/H3 were significantly less likely to experience sore throat (P < 0.001), malaise (P < 0.001), and muscle pain (P < 0.001); they were significantly more likely to have hypertension (P < 0.001), diabetes mellitus (P = 0.001), and chronic obstructive pulmonary disease (P < 0.001), delayed hospital presentation (P = 0.001), delayed oseltamivir treatment (P < 0.001), and higher in-hospital mortality (P = 0.02) than patients with pdm09 A/H1. Further comparison between severe pdm09 A/H1 and severe seasonal A/H3 revealed that severe seasonal A/H3 patients (median age, 71 years) were significantly older than patients with severe pdm09 A/H1 (median age, 7 years) (P < 0.001). Comparison between severe influenza and mild influenza, regardless of influenza A subtypes, by multivariate analysis, found that tachypnea (odds ratio [OR] = 44.3, 95% confidence interval [CI] = 15.7-124.6) and delayed oseltamivir therapy ≧ 48 hours after illness onset (OR = 3.7, 95% CI = 1.3-10.5) were independent risk factors for severe influenza. The findings of this study will improve the understanding of the clinical differences between pdm09 A/H1 and seasonal A/H3, and of influenza-associated complications and predictors for severe outcomes that can help to direct clinicians toward the most effective management of influenza patients to reduce the preventable mortality and morbidity.

Development of a Simple Clinical Risk Score for Early Prediction of Severe Dengue in Adult Patients.

We aimed to develop and validate a risk score to aid in the early identification of laboratory-confirmed dengue patients at high risk of severe dengue (SD) (i.e. severe plasma leakage with shock or respiratory distress, or severe bleeding or organ impairment). We retrospectively analyzed data of 1184 non-SD patients at hospital presentation and 69 SD patients before SD onset. We fit a logistic regression model using 85% of the population and converted the model coefficients to a numeric risk score. Subsequently, we validated the score using the remaining 15% of patients. Using the derivation cohort, two scoring algorithms for predicting SD were developed: models 1 (dengue illness ≤4 days) and 2 (dengue illness >4 days). In model 1, we identified four variables: age ≥65 years, minor gastrointestinal bleeding, leukocytosis, and platelet count ≥100×10(9) cells/L. Model 1 (ranging from -2 to +6 points) showed good discrimination between SD and non-SD, with an area under the receiver operating characteristic curve (AUC) of 0.848 (95% confidence interval [CI], 0.771-0.924). The optimal cutoff value for model 1 was 1 point, with a sensitivity and specificity for predicting SD of 70.3% and 90.6%, respectively. In model 2 (ranging from 0 to +3 points), significant predictors were age ≥65 years and leukocytosis. Model 2 showed an AUC of 0.859 (95% CI, 0.756-0.963), with an optimal cutoff value of 1 point (sensitivity, 80.3%; specificity, 85.8%). The median interval from hospital presentation to SD was 1 day. This finding underscores the importance of close monitoring, timely resuscitation of shock including intravenous fluid adjustment and early correction of dengue-related complications to prevent the progressive dengue severity. In the validation data, AUCs of 0.904 (95% CI, 0.825-0.983) and 0.917 (95% CI, 0.833-1.0) in models 1 and 2, respectively, were achieved. The observed SD rates (in both cohorts) were <3% for patients with a score <1 point, but >50% for those with a score of ≥2 points, irrespective of the day of illness onset, suggesting that our simple risk score can be easily implemented in resource-limited countries for early prediction of dengue patients at risk of SD provided that they have rapid dengue confirmed tests. For patients with other acute febrile illnesses or bacterial infections usually have SD risk score of >1. Thus, these scoring algorithms cannot totally replace good clinical judgement of the physician, and most importantly, early differentiating dengue from other febrile illnesses is critical for appropriate monitoring and management.

Utility of C-Reactive Protein Levels for Early Prediction of Dengue Severity in Adults.

Dengue has broad clinical presentation with unpredictable clinical evolution and outcome. We aimed to evaluate the utility of C-reactive protein (CRP) levels for distinguishing between mild and severe cases in the early phase of the dengue illness. We retrospectively evaluated adults with dengue from 2006 to 2014, according to 1997 and 2009 World Health Organization (WHO) criteria for severity. Of 191 included patients, 32.9% had nonshock dengue hemorrhagic fever (DHF), 3.1% dengue shock syndrome (DSS), and 7.9% severe dengue. The risk of DHF/DSS and severe dengue is significantly related to the increasing levels of CRP. Of 191 patients, 97 had CRP levels measured during the febrile (days 1-3); 85 during the critical (days 4-6); and 9 during the convalescent (days 7-10) illness phases. During the febrile phase, there was significant higher CRP level for DSS versus DF/nonshock DHF and severe dengue versus nonsevere dengue, with CRP cutoff level 30.1 mg/L (area under the receiver operating characteristic curve (AUC), 0.938; 100% sensitivity, 76.3% specificity) and 24.2 mg/L (AUC, 0.717; 70% sensitivity, 71.3% specificity), respectively. Our study highlights the utility of the CRP levels in early prediction of DSS and severe dengue in adult patients.

Clinical features of and risk factors for rhabdomyolysis among adult patients with dengue virus infection.

Among 1,076 dengue patients, 9 patients with rhabdomyolysis and 1,067 patients without rhabdomyolysis (controls) were retrospectively analyzed. Of nine patients with rhabdomyolysis, the most commonly reported symptom other than fever was myalgia; dengue hemorrhagic fever (DHF) was found in seven cases, and acute kidney injury was found in six cases. Furthermore, one (11.1%) patient died. The median duration from hospital admission to rhabdomyolysis diagnosis was 3 days. Patients with rhabdomyolysis had higher age, proportion of men, prevalence of hypertension, frequency of myalgia, and incidences of DHF, pleural effusion, and acute kidney injury than controls. Multivariate analysis showed that hypertension (odds ratio [OR] = 14.270), myalgia (OR = 20.377), and acute kidney injury (OR = 65.547) were independent risk factors for rhabdomyolysis. Comparison of cytokine/chemokine concentrations in 101 DHF patients, including those with (N = 4) and without (N = 97) rhabdomyolysis, showed that interleukin-6 and tumor necrosis factor-α levels were significantly increased in the former.

Clinical manifestations, laboratory findings and complications of pediatric scrub typhus in eastern Taiwan.

BACKGROUND: Scrub typhus is a clinically important endemic disease in Taiwan. The aims of this study were to analyze the clinical manifestations, laboratory data and complications of pediatric scrub typhus in eastern Taiwan. PATIENTS AND METHODS: We searched medical records for all patients with scrub typhus who were hospitalized between 1992 and 2002 at the Taitung branch of Mackay Memorial Hospital, Taiwan. Records of children under the age of 18 with a confirmed diagnosis were selected for retrospective review. RESULTS: During the study period, 145 patients fulfilled the diagnostic criteria for scrub typhus, of whom 106 (73%) were adults and 39 (27%) were children. The mean age of the children was 7.6+/-4.6 years. The most common clinical manifestations of pediatric scrub typhus were fever (n=39; 100%), cough (n=28; 72%), anorexia (72%), eschar (69%), chill (67%) and lymphadenopathy (64%). The most common complications were hepatic dysfunction (77%) and pneumonitis (54%). Three children (8%) required intensive care, but the overall survival rate was 97%. One child died with multi-organ failure within 8 hours after admission. CONCLUSION: Scrub typhus should be considered in children with fever and hepatic dysfunction, particularly in those with a history of environmental exposure in an endemic area for scrub typhus. The presence of an eschar offers an important diagnostic clue, but not for all cases. Children with scrub typhus may develop serious complications and may even die if appropriate treatment is not given. Doxycycline is an effective antibiotic for pediatric scrub typhus in Taiwan.

New phenylpropenoids, bis(1-phenylethyl)phenols, bisquinolinone alkaloid, and anti-inflammatory constituents from Zanthoxylum integrifoliolum.

Five new compounds, including two new phenylpropenoids, (R,E)-1-[4-(3-hydroxyprop-1-enyl)phenoxy]-3-methylbutane-2,3-diol (1) and 4-hydroxy-3-(3-methyl-2-butenyl)cinnamyl alcohol (2), two new bis(1-phenylethyl)phenols, 2,6-bis(1-phenylethyl)phenol (3) and 2,4-bis(1-phenylethyl)phenol (4), and a new bisquinolinone alkaloid, 18-demethylparaensidimerin C (5), together with 17 known compounds have been isolated from the stem wood of Zanthoxylum integrifoliolum. The structures of these new compounds were determined through spectral analyses including extensive 2D nuclear magnetic resonance data. Among the isolates, N-methylflindersine (7), (-)-simulanol (10), and evofolin-C (16) exhibited potent inhibition against N-formylmethionylleucylphenylalanine-induced superoxide production with IC(50) values less than 12 microM.

A new cytotoxic amide from the stem wood of Hibiscus tiliaceus.

A new coumarin, hibiscusin, and a new amide, hibiscusamide, together with eleven known compounds including vanillic acid, P-hydroxybenzoic acid, syringic acid, P-hydroxybenzaldehyde, scopoletin, N- trans-feruloyltyramine, N-cis-feruloyltyramine, a mixture of beta-sitosterol and stigmasterol, a mixture of beta-sitostenone and stigmasta-4,22-dien-3-one were isolated from the stem wood of Hibiscus tiliaceus. The structures of these new compounds were determined through spectral analyses. Among the isolates, three compounds exhibited cytotoxicity (IC (50) values < 4 microg/mL) against P-388 and/or HT-29 cell lines in vitro.