Metastasis is the predominant cause of death in breast cancer patients. Several lines of evidence have shown that microRNAs (miRs) can have an important role in cancer metastasis. Using isogenic ...pairs of low and high metastatic lines derived from a human breast cancer line, we have identified miR-149 to be a suppressor of breast cancer cell invasion and metastasis. We also identified GIT1 (G-protein-coupled receptor kinase-interacting protein 1) as a direct target of miR-149. Knockdown of GIT1 reduced migration/invasion and metastasis of highly invasive cells. Re-expression of GIT1 significantly rescued miR-149-mediated inhibition of cell migration/invasion and metastasis. Expression of miR-149 impaired fibronectin-induced focal adhesion formation and reduced phosphorylation of focal adhesion kinase and paxillin, which could be restored by re-expression of GIT1. Inhibition of GIT1 led to enhanced protein degradation of paxillin and α5β1 integrin via proteasome and lysosome pathways, respectively. Moreover, we found that GIT1 depletion in metastatic breast cancer cells greatly reduced α5β1-integrin-mediated cell adhesion to fibronectin and collagen. Low level of miR-149 and high level of GIT1 was significantly associated with advanced stages of breast cancer, as well as with lymph node metastasis. We conclude that miR-149 suppresses breast cancer cell migration/invasion and metastasis by targeting GIT1, suggesting potential applications of the miR-149-GIT1 pathway in clinical diagnosis and therapeutics.
Background
Pulsed radiofrequency (PRF) has been widely used to treat chronic pain, but the effectiveness and mechanisms in preventing early neuropathic pain have not been well explored. Even fewer ...knowledge is available in its impact on glia‐mediated nociceptive sensitization. This study aims to elucidate the modulation of PRF on nerve injury‐induced pain development and activation of spinal mitogen‐activated protein kinases (MAPKs).
Methods
In a rat spinal nerve ligation (SNL) model, a low‐volt PRF treatment was applied to the L5 dorsal root ganglion after nerve injury. Nociceptive behaviours were measured by von Frey and heat withdrawal tests at multiple time points. MAPK activations, including p‐ERK and p‐p38, as well as TNF‐α level in the spinal dorsal horn were assessed and the cell types that expressed MAPK activation were identified by double immunofluorescence staining.
Results
We found that SNL promptly induced neuropathic pain in the affected hind limb for over 1 week as well as increased p‐ERK and p‐p38 in the spinal dorsal horn. PRF significantly attenuated SNL‐induced mechanical allodynia and thermal hyperalgesia for 5–7 days. PRF also inhibited ERK and p38 activations, which were found majorly located within neurons and microglia, respectively. Besides, PRF significantly suppressed expression of TNF‐α in the spinal dorsal horn throughout the course.
Conclusions
Low‐volt PRF significantly ameliorated SNL‐induced acute pain. Inferentially, PRF may inhibit spinal sensitization by down‐regulating spinal MAPK activations and activation‐mediated cytokine release. We demonstrated that early PRF treatment in acute nerve injury helps to ameliorate neuropathic pain development.
Cloud condensation nuclei (CCN) concentrations were measured at Egbert, a rural site in Ontario, Canada during the spring of 2007. The CCN concentrations were compared to values predicted from the ...aerosol chemical composition and size distribution using κ-Köhler theory, with the specific goal of this work being to determine the hygroscopic parameter (κ) of the oxygenated organic component of the aerosol, assuming that oxygenation drives the hygroscopicity for the entire organic fraction of the aerosol. The hygroscopicity of the oxygenated fraction of the organic component, as determined by an Aerodyne aerosol mass spectrometer (AMS), was characterised by two methods. First, positive matrix factorization (PMF) was used to separate oxygenated and unoxygenated organic aerosol factors. By assuming that the unoxygenated factor is completely non-hygroscopic and by varying κ of the oxygenated factor so that the predicted and measured CCN concentrations are internally consistent and in good agreement, κ of the oxygenated organic factor was found to be 0.22±0.04 for the suite of measurements made during this five-week campaign. In a second, equivalent approach, we continue to assume that the unoxygenated component of the aerosol, with a mole ratio of atomic oxygen to atomic carbon (O/C) ≈ 0, is completely non-hygroscopic, and we postulate a simple linear relationship between κorg and O/C. Under these assumptions, the κ of the entire organic component for bulk aerosols measured by the AMS can be parameterised as κorg=(0.29±0.05)·(O/C), for the range of O/C observed in this study (0.3 to 0.6). These results are averaged over our five-week study at one location using only the AMS for composition analysis. Empirically, our measurements are consistent with κorg generally increasing with increasing particle oxygenation, but high uncertainties preclude us from testing this hypothesis. Lastly, we examine select periods of different aerosol composition, corresponding to different air mass histories, to determine the generality of the campaign-wide findings described above.
Measurements of submicron aerosol chemical composition were made over the central Arctic Ocean from 5 August to 8 September 2008 as a part of the Arctic Summer Cloud Ocean Study (ASCOS) using an ...aerosol mass spectrometer (AMS). The median levels of sulphate and organics for the entire study were 0.051 and 0.055 μ g m−3, respectively. Positive matrix factorisation was performed on the entire mass spectral time series and this enabled marine biogenic and continental sources of particles to be separated. These factors accounted for 33% and 36% of the sampled ambient aerosol mass, respectively, and they were both predominantly composed of sulphate, with 47% of the sulphate apportioned to marine biogenic sources and 48% to continental sources, by mass. Within the marine biogenic factor, the ratio of methane sulphonate to sulphate was 0.25 ± 0.02, consistent with values reported in the literature. The organic component of the continental factor was more oxidised than that of the marine biogenic factor, suggesting that it had a longer photochemical lifetime than the organics in the marine biogenic factor. The remaining ambient aerosol mass was apportioned to an organic-rich factor that could have arisen from a combination of marine and continental sources. In particular, given that the factor does not correlate with common tracers of continental influence, we cannot rule out that the organic factor arises from a primary marine source.
Background
Proton pump inhibitors (PPIs) have been known to induce type I hypersensitivity reactions. However, severe delayed‐type hypersensitivity reactions (DHR) induced by PPI, such as ...Stevens‐Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), or drug rash with eosinophilia and systemic symptoms (DRESS), are rarely reported. We conducted a study of a large series of PPI‐related DHR, followed up their tolerability to alternative anti‐ulcer agents, and investigated the T‐cell reactivity to PPI in PPI‐related DHR patients.
Methods
We retrospectively analyzed patients with PPI‐related DHR from multiple medical centers in Taiwan during the study period January 2003 to April 2016. We analyzed the causative PPI, clinical manifestations, organ involvement, treatment, and complications. We also followed up the potential risk of cross‐hypersensitivity or tolerability to other PPI after their hypersensitivity episodes. Drug lymphocyte activation test (LAT) was conducted by measuring granulysin and interferon‐γ to confirm the causalities.
Results
There were 69 cases of PPI‐related DHR, including SJS/TEN (n=27) and DRESS (n=10). The LAT by measuring granulysin showed a sensitivity of 59.3% and specificity of 96.4%. Esomeprazole was the most commonly involved in PPI‐related DHR (51%). Thirteen patients allergic to one kind of PPI could tolerate other structurally different PPI without cross‐hypersensitivity reactions, whereas three patients developed cross‐hypersensitivity reactions to alternative structurally similar PPI. The cross‐reactivity to structurally similar PPI was also observed in LAT assay.
Conclusions
PPIs have the potential to induce life‐threatening DHR. In patients when PPI is necessary for treatment, switching to structurally different alternatives should be considered.
The development of van der Waals heterostructures has introduced unconventional phenomena that emerge at atomically precise interfaces. For example, interlayer excitons in two-dimensional transition ...metal dichalcogenides show intriguing optical properties at low temperatures. Here we report on room-temperature observation of interface excitons in mixed-dimensional heterostructures consisting of two-dimensional tungsten diselenide and one-dimensional carbon nanotubes. Bright emission peaks originating from the interface are identified, spanning a broad energy range within the telecommunication wavelengths. The effect of band alignment is investigated by systematically varying the nanotube bandgap, and we assign the new peaks to interface excitons as they only appear in type-II heterostructures. Room-temperature localization of low-energy interface excitons is indicated by extended lifetimes as well as small excitation saturation powers, and photon correlation measurements confirm antibunching. With mixed-dimensional van der Waals heterostructures where band alignment can be engineered, new opportunities for quantum photonics are envisioned.
The aim of this study was to identify the risk factors associated with developing oral squamous cell carcinoma (OSCC) from surgically excised oral leukoplakia (OL) in patients with previous oral ...cavity cancer. Clinicopathological data of 84 patients who were treated for OL between July 2002 and July 2020 and who had previously received treatment for OSCC were reviewed retrospectively. The follow-up time ranged from 0.69 to 17.99 years (mean 6.78 ± 4.25 years). The overall cumulative malignant transformation rate was 25% and the annual transformation rate was 5.73%. Kaplan–Meier survival analysis and the log-rank test showed that Candida infection (P = 0.010) was a risk factor associated with malignant transformation. In the multivariate Cox regression analysis, tongue and floor of the mouth as the location of the leukoplakia (P = 0.039), multifocal lesions of OL (P = 0.047), and Candida infection (P = 0.018) were the three independent prognostic factors related to the development of OSCC from the treated OL. A cautious approach to OL of the tongue with Candida infection or multifocal disease in this group of patients would be appropriate.
Nanomaterials exhibit unique optical phenomena, in particular excitonic quantum processes occurring at room temperature. The low dimensionality, however, imposes strict requirements for conventional ...optical excitation, and an approach for bypassing such restrictions is desirable. Here we report on exciton transfer in carbon-nanotube/tungsten-diselenide heterostructures, where band alignment can be systematically varied. The mixed-dimensional heterostructures display a pronounced exciton reservoir effect where the longer-lifetime excitons within the two-dimensional semiconductor are funneled into carbon nanotubes through diffusion. This new excitation pathway presents several advantages, including larger absorption areas, broadband spectral response, and polarization-independent efficiency. When band alignment is resonant, we observe substantially more efficient excitation via tungsten diselenide compared to direct excitation of the nanotube. We further demonstrate simultaneous bright emission from an array of carbon nanotubes with varied chiralities and orientations. Our findings show the potential of mixed-dimensional heterostructures and band alignment engineering for energy harvesting and quantum applications through exciton manipulation.
Early response is a well-established predictor of positive outcomes at the end of psychological treatments for common mental disorders. There is some prior evidence that this conclusion also applies ...to eating disorders, including three meta-analyses, but no moderators of that relationship have been identified. However, a number of further papers have been published since, which might influence the size of the effect of early response or the potential role of moderating factors. This pre-registered systematic review presents a comprehensive examination of this literature. Three databases were searched (Scopus, PsycInfo, PubMed). In total, 33 eligible studies were included in a narrative synthesis, and 25 studies were included in random-effects meta-analysis. The majority (91%) of studies were rated as having low or moderate risk of bias. Approximately half of patients across clinical samples showed early response to psychological therapy, which was most often defined as reliable symptomatic improvement during the first four sessions. A significant and moderate association was found between early response and post-treatment outcomes (r = 0.41 95% CI: 0.32–0.481, p < .0001). Significant evidence of heterogeneity (Q28 = 136.42, p < .0001; I2 = 80.2%) was evident. The review was limited by the exclusion of grey literature and only 76% of studies provided sufficient statistical information for meta-analytic synthesis, although we found no significant evidence of publication bias, χ2(1) = 0.001, p = .97. Overall, evidence accumulated over twenty years establishes early response as the most robust predictor of treatment outcomes in the field of eating disorders. However, only half of patients show early change in this way. Further research is needed to determine whether there are patient or clinician characteristics that predict early response to psychological treatment for eating disorders.
•The early change literature has grown since last reviewed.•Early change predicts the outcome of psychotherapies for eating disorders, with moderate to strong effect sizes.•There is no evidence that any factors moderate the influence of early change on outcomes of eating disorders.
Background
Classifications of intraductal papillary mucinous neoplasm (IPMN) remain ambiguous, especially for the mixed type. Factors predicting malignancy remain unclear. The aim of this study was ...to evaluate the usefulness of factors predicting malignancy in the new international consensus guidelines for resection of branch duct‐type (BD)‐IPMN and to compare them with those in the previous version.
Methods
A prospectively collected database of patients with biopsy‐proven BD‐IPMN was analysed to compare factors between the first and second consensus guidelines, particularly as predictors of malignancy.
Results
Of 350 patients with BD‐IPMN, sensitivity (0·724) and balanced accuracy (0·751) of the second guidelines were superior to those (0·639 and 0·730) in the first version at the expense of slightly reduced specificity (0·779 versus 0·822 for the first version) by random forest models. Multiple logistic regression analysis showed that main pancreatic duct dilatation greater than 5 mm (hazard ratio (HR) 4·54, 95 per cent confidence interval 2·45 to 8·41; P < 0·001), mural nodules (HR 6·27, 3·27 to 12·01; P < 0·001) and carbohydrate antigen 19–9 level above 37 units/ml (HR 4·03, 1·83 to 8·90; P = 0·001) were independent predictors of BD‐IPMN malignancy.
Conclusion
The new consensus guidelines provide better sensitivity, performance of factors predicting malignancy, and balanced accuracy in the diagnosis of BD‐IPMN malignancy. Size alone was limited in predicting malignancy. Variability in clinical significance of the individual factors associated with a risk of malignancy indicates the need for a tailored approach in the management of patients with BD‐IPMN.
Cyst size alone is not useful
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