Electrochemical synthesis of sulfonated benzothiophenes using 2-alkynylthioanisoles and sodium sulfinates.

Electrochemical sulfonylation/cyclization of 2-alkynylthioanisoles with sodium sulfinates was developed under catalyst-, external oxidant- and metal-free conditions. The electrosynthesis provides sustainable and efficient access to 3-sulfonated benzothiophenes with good substrate scope and functional group tolerance. This cascade radical process has been triggered through a sulfonyl radical addition to alkynes using sodium sulfinates under electrochemical conditions.

Cross-sectional study of asymptomatic Neisseria gonorrhoeae and Chlamydia trachomatis infections in sexually transmitted disease related clinics in Shenzhen, China.

The aims of this study were to investigate the prevalence and proportion of laboratory-confirmed urethral Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) infections that were asymptomatic among individuals presenting to clinics in Shenzhen and the risk factors related to asymptomatic CT infection. In a cross-sectional study, eligible individuals were invited to participate in the questionnaire, and urine specimens were collected to identify CT and NG infections using a nucleic acid amplification test (NAAT). Considering the differences in the presentation of symptoms between men and women, this study was stratified by gender. Corresponding outcomes were analyzed by Chi-square test and multivariate logistic regression. A total of 2,871 participants were asymptomatic and included in our analyses: 1120 (39.0%) men and 1751 (61.0%) women. The prevalence of asymptomatic NG and CT infections was 0.9% and 6.2% in men, and 0.4% and 7.9% in women, respectively. The proportion of asymptomatic urethral CT among men with urethral CT was 28.3%; for women, it was 34.2%. For asymptomatic men with CT, 3 independent risk factors were identified: (1) men under the age of 30 (aOR, 1.83; 95% CI, 1.11-3.03); (2) being employed in the commercial service work (2.82; 1.36-5.84); and (3) being recruited through the urological department (2.12; 1.19-3.79). For asymptomatic women with urethral CT, age less than 30 years was a risk factor. In conclusion, a substantial prevalence of asymptomatic CT infections was found among men and women presenting to clinics in Shenzhen. The significant correlation between asymptomatic CT infection and these risk factors could help identify high-risk populations and guide screening.

Discontinuation of Tyrosine Kinase Inhibitors in Chronic Myeloid Leukemia With Losing Major Molecular Response as a Definition for Molecular Relapse: A Systematic Review and Meta-Analysis.

Background: A new goal in treatment of chronic myeloid leukemia (CML) in patients with stable deep molecular response (DMR) is maintaining durable treatment-free remission (TFR) after discontinuing tyrosine kinase inhibitor (TKI) treatment. Methods: We conducted a systematic review and meta-analysis focusing on the efficacy and safety of TKI discontinuation but also exploring the factors contributing to successful TFR. Results: The search yielded 10 trials including 1,601 patients. For patients who discontinued TKIs, the estimated weighted mean incidence of major molecular relapse was 16% (95%CI: 11-21), 34% (95%CI: 29-38), 39% (95%CI: 35-43) and 41% (95%CI: 36-47) at 3, 6, 12, and 24 months, respectively. Of these, 39, 82, and 95% of molecular losses occurred within the first 3, 6, and 12 months. In safety analysis, among patients without TFR, 98% (95% CI: 96-100) were sensitive to TKI retreatment. No new safety issues were identified except TKI withdrawal syndrome, which appeared during the early TFR phase, with a weighted mean incidence of 27% (95%CI: 19-35). Our subgroup analysis suggested better TFR associated with interferon therapy (P = 0.007), depth of molecular response (P = 0.018) and duration of DMR (P < 0.001). Conclusions: TFR as an extension of an approach to optimize management of CML is clinically feasible in approximately 59% of patients with sufficient TKI response. In the remaining 41% of patients with molecular relapse, discontinuing TKIs had no negative impact on clinical outcomes. Given the high heterogeneity among studies, the role of these predictors for successful TFR still requires further investigation.

First-line treatment strategies for newly diagnosed chronic myeloid leukemia: a network meta-analysis.

OBJECTIVES: With bosutinib proven to be available for frontline treatment, there are currently four frontline treatments as well as an additional strategy with high-dose imatinib for newly diagnosed chronic myeloid leukemia (CML). Due to the lack of direct comparison of high-dose imatinib, dasatinib, nilotinib, and bosutinib, we summarized the evidence to indirectly compare the efficacy among these treatment options. METHODS: In total, 14 randomized clinical trials including 5,630 patients were analyzed by direct and mixed-treatment comparisons. Outcomes assessed were the following: complete cytogenetic response at 12 months; major molecular response at 12, 24, and 36 months; deep molecular response at 12, 24, 36, and 60 months; early molecular response at 3 months; progression-free survival (PFS); overall survival (OS); and Grade 3 or 4 adverse events (AEs). RESULTS: The Bayesian network meta-analysis demonstrated that high-dose imatinib was less effective than all new-generation tyrosine kinase inhibitors and had a higher probability of Grade 3 or 4 AEs. For molecular response, 300 mg of nilotinib was likely to be the preferred frontline treatment, as demonstrated by higher response rates and faster, deeper, and longer molecular response. For PFS and OS, there were high likelihoods (79% and 74%, respectively) that 400 mg of nilotinib was the preferred option. For AEs, standard-dose imatinib has the highest probability (65%) of being the most favorable toxicity profile. CONCLUSION: Considering the efficacy and toxicity profile, it is not recommended to use high-dose imatinib for treatment. This analysis also showed that nilotinib has the highest probability to become the preferred frontline agents for treating CML.

Tunable synchronously-pumped fiber Raman laser in the visible and near-infrared exploiting MOPA-generated rectangular pump pulses.

We report a tunable synchronously pumped fiber Raman laser (SPFRL) in the near-infrared (NIR) and visible wavebands pumped by a pulsed, all-fiber PM 1060 nm master oscillator power amplifier (MOPA) and its frequency-doubled output, respectively. The seed was adaptively shaped to deliver rectangular output pulses, thereby enabling selective excitation of individual Raman Stokes lines. Using filtered synchronous feedback of the desired Raman Stokes line, the linewidth of the SPFRL was reduced by a factor of 4 and the extinction ratio of the desired Raman Stokes was improved by more than 3 dB relative to a simple single-pass conversion scheme. A continuous tuning range of 2.2 THz was obtained for each of the Raman Stokes orders in the visible (spanning from green to orange-first to fifth Stokes lines). A larger 5.0 THz tunable range was achieved in the NIR spectral region.

Selective excitation of multiple Raman Stokes wavelengths (green-yellow-red) using shaped multi-step pulses from an all-fiber PM MOPA.

We report a rapidly tunable, wavelength agile fiber laser system capable of the synchronous generation of sequences of pulses with different wavelengths in the visible region of the spectrum using stimulated Raman scattering of multi-step pump pulses in a 250 m length of fiber. The frequency doubled output of a single polarization all-fiber Yb-doped MOPA operating at 1060 nm was used as the pump source. By adjusting the pump power and the pulse profiles we achieved the sequential excitation of green (1st Stokes), yellow (4th Stokes) and red light (6th Stokes) using 3-step pulses, or the combination of any two using 2-step pulses. The wavelength switching time was <5 ns and was limited only by the pulse shaping drive electronics.

Polarisation maintaining 100W Yb-fiber MOPA producing microJ pulses tunable in duration from 1 to 21 ps.

This paper demonstrates a single polarisation, 1.06 microm Yb-doped fiber MOPA, delivering 21 ps pulses in a diffraction limited beam at repetition rates of up to 908 MHz and average output power of 100 W. The maximum pulse energy was 1.7 microJ at a repetition rate of 56 MHz, with corresponding peak power of 85 kW. The 100 W power was limited by available diode pump power and scaling to higher power levels is discussed. We also report self-phase-modulation based pulse compression which produced pulse durations as short as 1.1 ps from an external grating compressor. Using 4.2 ps pulses at a repetition rate of 227 MHz enabled 26 W of visible laser power (50% SHG efficiency) to be demonstrated.

Excitation of individual Raman Stokes lines in the visible regime using rectangular-shaped nanosecond optical pulses at 530 nm.

We demonstrate the selective excitation of individual Raman Stokes lines of up to the ninth order by pumping with rectangular-shaped optical pulses at 530 nm from a frequency-doubled adaptively pulse shaped fiber master oscillator power amplifier. We achieve extinction ratios of up to 15 dB between selected and adjacent Raman orders in a 1-km-long fiber.

Picosecond fiber MOPA pumped supercontinuum source with 39 W output power.

We report a picosecond fiber MOPA pumped supercontinuum source with 39 W output, spanning at least 0.4-2.25 microm at a repetition rate of 114.8 MHz. The 2m long PCF had a large, 4.4 microm diameter core and a high-delta design which led to an 80% coupling efficiency, high damage threshold and rapid generation of visible continuum generation from the picosecond input pulses. The high and relatively uniform power density across the visible spectral region was approximately 31.7 mW/nm corresponding to peak power density of approximately 12.5 W/nm for the 21 ps input pulses. The peak power density was increased to 26.9 W/nm by reducing the repetition rate to 28 MHz. This represents an increase in both average and peak power compared to previously reported visible supercontinuum sources from either CW pumped or pulsed-systems.

High power pulsed fiber MOPA system incorporating electro-optic modulator based adaptive pulse shaping.

We demonstrate active pulse shaping using an Electro-Optic Modulator in order to compensate the pulse shaping effects caused by Gain Saturation in a high power Yb doped fiber amplifier chain and to generate various custom-defined output pulse shapes. Square, step and smooth pulse shapes are achieved, with mJ pulse energies. Use of a modulator to shape pulses rather than direct modulation of the diode drive current allows us to eliminate undesired transients due to laser start up dynamics. The required shaping is calculated based on a simple measurement of amplifier performance, and does not require detailed modeling of the amplifier dynamics.