Patients who complete neoadjuvant chemotherapy for breast cancer without a pathological complete response have a high risk of relapse. A randomized trial comparing capecitabine with no additional ...adjuvant therapy showed that capecitabine prolonged disease-free and overall survival.
Patients who have residual invasive breast cancer after the receipt of neoadjuvant chemotherapy have a high risk of relapse.
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The rate of complete response as assessed on pathological testing (hereafter, pathological complete response) ranges from 13 to 22% among patients with human epidermal growth factor receptor 2 (HER2)–negative primary breast cancer.
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Patients who do not have a pathological complete response after the receipt of neoadjuvant taxane and anthracycline chemotherapy have a 20 to 30% risk of relapse.
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Patients with HER2-negative cancer who receive neoadjuvant chemotherapy often receive postoperative radiation therapy, whereas endocrine therapy is administered to patients with hormone-receptor–positive disease . . .
Methanol, being electron rich and derivable from methane or CO2, is a potentially renewable one-carbon (C1) feedstock for microorganisms. Although the ribulose monophosphate (RuMP) cycle used by ...methylotrophs to assimilate methanol differs from the typical sugar metabolism by only three enzymes, turning a non-methylotrophic organism to a synthetic methylotroph that grows to a high cell density has been challenging. Here we reprogrammed E. coli using metabolic robustness criteria followed by laboratory evolution to establish a strain that can efficiently utilize methanol as the sole carbon source. This synthetic methylotroph alleviated a so far uncharacterized hurdle, DNA-protein crosslinking (DPC), by insertion sequence (IS)-mediated copy number variations (CNVs) and balanced the metabolic flux by mutations. Being capable of growing at a rate comparable with natural methylotrophs in a wide range of methanol concentrations, this synthetic methylotrophic strain illustrates genome editing and evolution for microbial tropism changes and expands the scope of biological C1 conversion.
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•E. coli was engineered to grow on methanol alone by rational design and evolution•A doubling time of 8.5 h and maximum OD of 2 were achieved•Formaldehyde-induced DNA-protein crosslinking was identified and solved•Copy number variation of a region spanning 70kb facilitates carbon source shifts
Chen et al. demonstrate genetic reprogramming of E. coli to efficiently grow with methanol as the sole carbon source.
Polystyrene (PS) dissolved in the mixture of tetrahydrofuran (THF) and
N,
N-dimethyl formamide (DMF) was electrospun to prepare fibers of sub-micron in diameters. Electropinning parameters such as ...polymer concentration, applied voltage and tip-to-collector distance were controlled. From these parameters it was determined that while the surface tension of polymer solution had linear correlation with the critical voltage, throughput was dependent on electric conductivity. The electrospun PS fibers produced contained irregular beads and electrospinning certainly was enhanced with increasing DMF content. The bead concentration was also controlled by DMF content. The aspect ratio of the formed beads and the diameter of fibers were increased with increasing solution concentration. When PS was dissolved in only THF, an unexpected half hollow spheres (HHS) structure appeared. Also, different shape forms of PS non-woven mats have been prepared by controlling electrospinning parameters.
Given the mode of transmission of Middle East respiratory syndrome (MERS), healthcare workers (HCWs) in contact with MERS patients are expected to be at risk of MERS infections. We evaluated the ...prevalence of MERS coronavirus (CoV) immunoglobulin (Ig) G in HCWs exposed to MERS patients and calculated the incidence of MERS-affected cases in HCWs. We enrolled HCWs from hospitals where confirmed MERS patients had visited. Serum was collected 4 to 6 weeks after the last contact with a confirmed MERS patient. We performed an enzyme-linked immunosorbent assay (ELISA) to screen for the presence of MERS-CoV IgG and an indirect immunofluorescence test (IIFT) to confirm MERS-CoV IgG. We used a questionnaire to collect information regarding the exposure. We calculated the incidence of MERS-affected cases by dividing the sum of PCR-confirmed and serology-confirmed cases by the number of exposed HCWs in participating hospitals. In total, 1169 HCWs in 31 hospitals had contact with 114 MERS patients, and among the HCWs, 15 were PCR-confirmed MERS cases in study hospitals. Serologic analysis was performed for 737 participants. ELISA was positive in five participants and borderline for seven. IIFT was positive for two (0.3%) of these 12 participants. Among the participants who did not use appropriate personal protective equipment (PPE), seropositivity was 0.7% (2/294) compared to 0% (0/443) in cases with appropriate PPE use. The incidence of MERS infection in HCWs was 1.5% (17/1169). The seroprevalence of MERS-CoV IgG among HCWs was higher among participants who did not use appropriate PPE.
Non-variceal upper gastrointestinal bleeding remains an important emergency condition, leading to significant morbidity and mortality. As endoscopic therapy is the 'gold standard' of management, ...treatment of these patients can be considered in three stages: pre-endoscopic treatment, endoscopic haemostasis and post-endoscopic management. Since publication of the Asia-Pacific consensus on non-variceal upper gastrointestinal bleeding (NVUGIB) 7 years ago, there have been significant advancements in the clinical management of patients in all three stages. These include pre-endoscopy risk stratification scores, blood and platelet transfusion, use of proton pump inhibitors; during endoscopy new haemostasis techniques (haemostatic powder spray and over-the-scope clips); and post-endoscopy management by second-look endoscopy and medication strategies. Emerging techniques, including capsule endoscopy and Doppler endoscopic probe in assessing adequacy of endoscopic therapy, and the pre-emptive use of angiographic embolisation, are attracting new attention. An emerging problem is the increasing use of dual antiplatelet agents and direct oral anticoagulants in patients with cardiac and cerebrovascular diseases. Guidelines on the discontinuation and then resumption of these agents in patients presenting with NVUGIB are very much needed. The Asia-Pacific Working Group examined recent evidence and recommends practical management guidelines in this updated consensus statement.
Background
Conventional anorectal manometric parameters based on linear waves cannot properly predict balloon expulsion (BE) time. We aimed to determine the correlation between integrated pressurized ...volume (IPV) parameters during simulated evacuation (SE) and BE time in healthy individuals and constipated patients and to assess the correlation between each parameter and symptoms.
Methods
A total of 230 male participants (including 26 healthy volunteers and 204 chronically constipated patients) underwent high‐resolution anorectal manometry (HRAM) and BE tests. The IPV was calculated by multiplying the amplitude, distance, and time from the HRAM profile. Receiver operating characteristic curve (ROC) analysis and partial least square regression (PLSR) were performed.
Key Results
ROC analysis indicated that the IPV ratio between the upper 1 cm and lower 4 cm of the anal canal was more effective for predicting BE time (area under the curve AUC: 0.74, 95% confidence interval CI: 0.67‐0.80, P < .01) than the conventional anorectal parameters, including defecation index and rectoanal gradient (AUC: 0.60, 95% CI: 0.52‐0.67, P = .01). PLSR analysis of a linear combination of IPV parameters yielded an AUC of 0.79. Moreover, the IPV ratio showed a greater clinical correlation with patient symptoms than conventional parameters.
Conclusions and Inferences
The IPV parameters and the combination of IPV parameters via PLSR were more significantly correlated with BE time than the conventional parameters. Thus, this study presents a useful diagnostic tool for the evaluation of pathophysiologic abnormalities in dyssynergic defecation using IPV and BE time.
The novel integrated pressurized volume (IPV) parameters and the combination of IPV parameters via partial least square regression were more significantly correlated with balloon expulsion (BE) time than the conventional parameters. IPV parameters can be useful diagnostic tools for the evaluation of pathophysiologic abnormalities in dyssynergic defecation using high‐resolution anorectal manometry and BE tests.
The medicinal fungi Inonotus xeranticus and Phellinus linteus in the family Hymenochaetaceae have been used as traditional medicines for the treatment of various diseases. However, the compound ...responsible for the antioxidant activity is still unknown. Therefore, this study was conducted to characterize the antioxidant substances present in cultured broths made from these fungi. Antioxidant fractions of the cultured broths obtained from I. xeranticus and P. linteus were analysed using reversed-phase HPLC, which revealed several peaks that exhibited a potent free radical scavenging activity. To identify these antioxidant peaks, an I. xeranticus strain was mass-cultured, and the cultured broth was separated using antioxidant activity-guided fractionation. Four major active substances were purified and identified as hispidin and its dimers, 3,14'-bihispidinyl, hypholomine B, and 1,1-distyrylpyrylethan based on spectroscopic analyses. All compounds exhibited a significant scavenging activity against these radical species in a concentration-dependent manner. Antioxidant substances found in the cultured broths of the medicinal fungi I. xeranticus and P. linteus were identified as hispidin and its dimers, 3,14'-bihispidinyl, hypholomine B, and 1,1-distyrylpyrylethan. Polyphenol antioxidants were isolated from the cultured broth of the medicinal fungi I. xeranticus and P. linteus and identified based on extensive spectroscopic analyses. These compounds exhibited a strong antioxidant activity.
We analyze an ensemble of microlensing events from the 2015 Spitzer microlensing campaign, all of which were densely monitored by ground-based high-cadence survey teams. The simultaneous observations ...from Spitzer and the ground yield measurements of the microlensing parallax vector , from which compact constraints on the microlens properties are derived, including 25% uncertainties on the lens mass and distance. With the current sample, we demonstrate that the majority of microlenses are indeed in the mass range of M dwarfs. The planet sensitivities of all 41 events in the sample are calculated, from which we provide constraints on the planet distribution function. In particular, assuming a planet distribution function that is uniform in , where q is the planet-to-star mass ratio, we find a 95% upper limit on the fraction of stars that host typical microlensing planets of 49%, which is consistent with previous studies. Based on this planet-free sample, we develop the methodology to statistically study the Galactic distribution of planets using microlensing parallax measurements. Under the assumption that the planet distributions are the same in the bulge as in the disk, we predict that ∼1/3 of all planet detections from the microlensing campaigns with Spitzer should be in the bulge. This prediction will be tested with a much larger sample, and deviations from it can be used to constrain the abundance of planets in the bulge relative to the disk.
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