Etiology and Clinical Characteristics of Influenza-Like Illness (ILI) in Outpatients in Beijing, June 2010 to May 2011

BACKGROUND: Since May 2009, exposure of the population of Beijing, China to pH1N1 has resulted in an increase in respiratory illnesses. Limited information is available on the etiology and clinical characteristics of the influenza-like illness (ILI) that ensued in adults following the pH1N1 pandemic. METHODS: Clinical and epidemiological data of ILI in adults was collected. A total of 279 throat swabs were tested for twelve respiratory viruses using multiplex RT-PCR. Clinical characteristics of influenza A in outpatients versus test-negative patients were compared using Pearson's χ2 and the Mann-Whitney U test. 190 swabs were tested for pH1N1 by virus isolation. Consultation rates for ILI were compared between 2009 and 2010. RESULTS: One or two virus were detected in 29% of the samples. Influenza A virus (FLU-A) accounted for 22.9% (64/279). Other viruses were present at a frequency less than 3.0%. Cough was significantly associated with Influenza A virus infection (χ2, p<0.001). The positive rate of FLU-A was consistent with changes in the ILI rate during the same period and there was a significant reduction in the incidence of ILI in 2010 when compared to 2009. During the 2010-2011 influenza season, the incidence peaked in January 2011 in Beijing and north China. CONCLUSIONS: Exposure to pH1N1 had no impact on typical influenza seasonal peaks, although FLU-A remained the predominant virus for 2010 in Beijing. Symptomatically, cough was associated with FLU-A infection. The positive rate of influenza virus was consistent with changes in the ILI rate during the same period and there was a significant reduction in the incidence of ILI in 2010 when compared to that of 2009

Can Programming Languages Boost Each Other via Instruction Tuning?

When human programmers have mastered a programming language, it would be easier when they learn a new programming language. In this report, we focus on exploring whether programming languages can boost each other during the instruction fine-tuning phase of code large language models. We conduct extensive experiments of 8 popular programming languages (Python, JavaScript, TypeScript, C, C++, Java, Go, HTML) on StarCoder. Results demonstrate that programming languages can significantly improve each other. For example, CodeM-Python 15B trained on Python is able to increase Java by an absolute 17.95% pass@1 on HumanEval-X. More surprisingly, we found that CodeM-HTML 7B trained on the HTML corpus can improve Java by an absolute 15.24% pass@1. Our training data is released at https://github.com/NL2Code/CodeM.Comment: Work in progres

Potential drug-drug interaction of olverembatinib (HQP1351) using physiologically based pharmacokinetic models

Olverembatinib (HQP1351) is a third-generation BCR-ABL tyrosine kinase inhibitor for the treatment of chronic myeloid leukemia (CML) (including T315I-mutant disease), exhibits drug-drug interaction (DDI) potential through cytochrome P450 (CYP) enzymes CYP3A4, CYP2C9, CYP2C19, CYP1A2, and CYP2B6. A physiologically-based pharmacokinetic (PBPK) model was constructed based on physicochemical and in vitro parameters, as well as clinical data to predict 1) potential DDIs between olverembatinib and CYP3A4 and CYP2C9 inhibitors or inducers 2), effects of olverembatinib on the exposure of CYP1A2, CYP2B6, CYP2C9, CYP2C19, and CYP3A4 substrates, and 3) pharmacokinetics in patients with liver function injury. The PBPK model successfully described observed plasma concentrations of olverembatinib from healthy subjects and patients with CML after a single administration, and predicted olverembatinib exposure increases when co-administered with itraconazole (strong CYP3A4 inhibitor) and decreases with rifampicin (strong CYP3A4 inducer), which were validated by observed data. The predicted results suggest that 1) strong, moderate, and mild CYP3A4 inhibitors (which have some overlap with CYP2C9 inhibitors) may increase olverembatinib exposure by approximately 2.39-, 1.80- to 2.39-, and 1.08-fold, respectively; strong, and moderate CYP3A4 inducers may decrease olverembatinib exposure by approximately 0.29-, and 0.35- to 0.56-fold, respectively 2); olverembatinib, as a “perpetrator,” would have no or limited impact on CYP1A2, CYP2B6, CYP2C9, CYP2C19, and CYP3A4 enzyme activity 3); systemic exposure of olverembatinib in liver function injury with Child-Pugh A, B, C may increase by 1.22-, 1.79-, and 2.13-fold, respectively. These simulations inform DDI risk for olverembatinib as either a “victim” or “perpetrator”

Comparative whole-genome analysis reveals artificial selection effects on Ustilago esculenta genome

Ustilago esculenta, infects Zizania latifolia, and induced host stem swollen to be a popular vegetable called Jiaobai in China. It is the long-standing artificial selection that maximizes the occurrence of favourable Jiaobai, and thus maintaining the plant-fungi interaction and modulating the fungus evolving from plant pathogen to entophyte. In this study, whole genome of U. esculenta was sequenced and transcriptomes of the fungi and its host were analysed. The 20.2Mb U. esculenta draft genome of 6,654 predicted genes including mating, primary metabolism, secreted proteins, shared a high similarity to related Smut fungi. But U. esculenta prefers RNA silencing not repeat-induced point in defence and has more introns per gene, indicating relatively slow evolution rate. The fungus also lacks some genes in amino acid biosynthesis pathway which were filled by up-regulated host genes and developed distinct amino acid response mechanism to balance the infection-resistance interaction. Besides, U. esculenta lost some surface sensors, important virulence factors and host range-related effectors to maintain the economic endophytic life. The elucidation of the U. esculenta genomic information as well as expression profiles can not only contribute to more comprehensive insights into the molecular mechanism underlying artificial selection but also into smut fungi-host interactions

Noncontact Conjunctiva: A Better Mitomycin C Application Site for Trabeculectomy

Abstract Introduction Bleb scarring is the most important complication of trabeculectomy. Changing the application position of mitomycin C (MMC) during trabeculectomy might affect the surgery outcome. Our aim is to compare the effectiveness and safety of intraocular pressure (IOP) lowering in two different application sites of mitomycin in trabeculectomy. Methods This retrospective trial compared the surgical outcomes of 177 eyes that underwent trabeculectomy with adjunctive mitomycin C. In 70 eyes, an MMC-soaked sponge was applied under the scleral flap without touching Tenon’s capsule. In 107 eyes, an MMC-soaked sponge was applied under the scleral flap covered by Tenon’s capsule. Outcome measures were the IOP, best-corrected visual acuity (BCVA), success rates, and incidence of complications. Results Within both groups, a highly significant IOP reduction was seen during follow-up. The effectiveness in reducing IOP and the change in best-corrected visual acuity (BCVA) were similar between the two groups. Thin-walled blebs and postoperative hypotony were seen more often when MMC-soaked sponges were applied under the scleral flap covered by Tenon’s capsule (P = 0.008 and P = 0.012, respectively). There was no significant difference in BCVA or other complications in either group. Conclusion Since the effectiveness of IOP reduction was similar between both groups and with a low incidence of thin-walled blebs and hypotony, the subscleral application without touching Tenon’s capsule seems to be the safer application site of MMC during trabeculectomy

Circular RNA hsa_circ_0067842 facilitates tumor metastasis and immune escape in breast cancer through HuR/CMTM6/PD-L1 axis

Abstract Background Circular RNAs (circRNAs) have been shown to play diverse biological functions in the progression of multiple diseases. However, the impacts of circRNAs on breast cancer (BC) progression remains unclear. Therefore, the objective of this paper is to investigate the role and mechanisms of a functional circRNA in BC metastasis and immune escape. Methods This study used a circRNA microarray and identified a novel circRNA hsa_circ_0067842. The validation and characteristics of hsa_circ_0067842 were investigated using qRT-PCR, sanger sequencing, RNase R treatment, actinomycin D treatment and fluorescence in situ hybridization (FISH). Gain- and loss-of-function assays were performed to evaluate the biological function of hsa_circ_0067842 in BC progression and immune escape. Mechanistically, the interaction between hsa_circ_0067842 and HuR was explored by RNA pull down, mass spectrometry (MS), subcellular component protein extraction and immunofluorescence (IF). The regulatory mechanisms of hsa_circ_0067842/HuR/CMTM6/PD-L1 axis were investigated by qRT-PCR, western blot, FISH, immunoprecipitation and rescue assays. Results The expression of hsa_circ_0067842 was upregulated in BC tissues and cells, which was found to be significantly associated with poor prognosis, regardless of other clinical covariates. Function assays showed that hsa_circ_0067842 promoted the migration and invasion capacities of BC cells. Moreover, co-culture experiment with peripheral blood mononuclear cells (PBMCs) showed that hsa_circ_0067842 played a role in the immune escape of BC cells. Mechanistically, our study showed that hsa_circ_0067842 interacted with HuR, affecting its nuclear translocation, thus enhancing the stability of CMTM6. CMTM6 not only enhances the migration and invasion ability of BC cells, but also affects the ubiquitination of PD-L1 and inhibits its degradation. Conclusion Collectively, our results demonstrated that hsa_circ_0067842 promoted BC progression through the HuR/CMTM6/PD-L1 axis, providing new insight and a potential target for BC prognosis and therapy

ILI rates in North China from June 2009 to May 2010 and June 2010 to May 2011.

<p>The weekly ILI rate increased rapidly in the 35^th week of 2009 in North China, with the highest weekly ILI rate of 12.1 cases per 100 consultations occurring in the 44^th week. However, the rate was relatively stable on the basis of the weekly ILI surveillance system of North China in 2010. The incidence rose slightly in January 2011 and the usual influenza seasonal peak appeared in the 5^th week of 2011. The percentage of patient visits for ILI peaked at 5.0% in the influenza 2010–2011 season. ^▴The ILI rate of North China derived from data obtained from the Chinese National Influenza Center (CNIC).</p

Monthly distribution of test-positive virus in the PKU People' hospital from June 2010 to May 2011.

<p><a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0028786#pone-0028786-g001" target="_blank">Figure 1A</a> shows the number of respiratory specimens testing positive for influenza, by influenza type and positive rates of respiratory virus. Panel B shows the smaller number of other viruses. The rate of positive cases of the virus gradually increased from August to October, slowly decreased in November, and then increased again in January 2011. The peak of the positive rate occurred in January 2011 and influenza was the predominant virus between August 2010 and March 2011. Particularly in August, September and October 2010, and March 2011, all infections were caused by FLU only( <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0028786#pone-0028786-g001" target="_blank">Figure 1B</a>). The number of positive cases of influenza virus increased rapidly in September and peaked in January 2011, following which it then decreased to normal levels in March 2011. Influenza A(H3) was the predominant viral etiological factor and was only observed from July to December 2010, and again, in January 2011, Influenza A(H3) were replaced by 2009 H1N1. 2009 H1N1 peaked in January 2011. Most influenza viruses were in fact influenza A, with influenza B virus only observed in April 2011. In June, multiple infections predominated. Each identified ILI was caused by a single virus except in June, July and November 2010 and January and February 2011: two FLU-A in August, eight FLU-A in September and in October each, eight FLU-A and one HRCV229E/NL63 in December, four FLU-A in March 2011, one FLU-A, two FLU-B and one ADV in April 2011, No virus was detected in May 2011. On the other hand, two of the three identified ILI samples in June were mixed infections, HRSV and HRV. Other double infections included: One HRCV/FLU-A in July, one FLU-A/HRV in November, two HRSV-A and FLU-A and one HRSV-A and HRV and FLU-A in January 2011, one HRSV-A and HRV and FLU-A in February 2011.</p

Clinical characteristics of ILI-patients in PKU People' Hospital between June 2010 and May 2011.

<p>Values are median (IQR) or n (%) of patients unless otherwise stated. Normally distributed data are reported as means with 95% CI and non-normally distributed data as medians with interquartile range.</p><p>The characteristics contain demography characteristics, medical history, presenting symptoms, and clinical findings.</p><p>*Positive cases for at least one respiratory virus except Influenza A viruses by RT-PCT.</p><p>**Telephone follow-up data mainly for RT-PCR-positive patients.</p>##<p>Includes all ILI cases regardless of virology RT-PCR test results.</p

The adult outpatient service capacity of the Infectious Diseases Department of PKUPH, 2009–2011.

<p>In 2010, the overall number of outpatients was less than that of 2009, particularly between May and December. From May 2009, when pH1N1 emerged in Beijing, the capacity of the outpatient service of the Infectious Diseases Department of PKU People's Hospital increased rapidly. The number of outpatients peaked in November 2009, following which. The volume declined to reach normal levels in the third month of 2010. The numbers of outpatients was relatively stable in 2010, with an increase during November and December and a further peak in January 2011.</p