ABSTRACT
We present Herschel Space Observatory Photodetector Array Camera and Spectrometer (PACS) and Spectral and Photometric Imaging Receiver Fourier Transform Spectrometer (SPIRE FTS) spectroscopy ...of a sample of 20 massive Young Stellar Objects (YSOs) in the Large and Small Magellanic Clouds (LMC and SMC). We analyse the brightest far-infrared (far-IR) emission lines, that diagnose the conditions of the heated gas in the YSO envelope and pinpoint their physical origin. We compare the properties of massive Magellanic and Galactic YSOs. We find that O i and C ii emission, that originates from the photo-dissociation region associated with the YSOs, is enhanced with respect to the dust continuum in the Magellanic sample. Furthermore the photoelectric heating efficiency is systematically higher for Magellanic YSOs, consistent with reduced grain charge in low metallicity environments. The observed CO emission is likely due to multiple shock components. The gas temperatures, derived from the analysis of CO rotational diagrams, are similar to Galactic estimates. This suggests a common origin to the observed CO excitation, from low-luminosity to massive YSOs, both in the Galaxy and the Magellanic Clouds. Bright far-IR line emission provides a mechanism to cool the YSO environment. We find that, even though O i, CO, and C ii are the main line coolants, there is an indication that CO becomes less important at low metallicity, especially for the SMC sources. This is consistent with a reduction in CO abundance in environments where the dust is warmer due to reduced ultraviolet-shielding. Weak H2O and OH emission is detected, consistent with a modest role in the energy balance of wider massive YSO environments.
This study was performed to evaluate the subjective and objective functional outcomes of patients who had undergone submandibular gland-sparing neck dissection. All data were obtained from patients ...treated in a single hospital. Seventy-seven patients who had undergone complete submandibular gland sparing (CSGS) were included in the study. Cancer prognosis items were recorded. The subjective outcomes included patient self-evaluation of mouth dryness and the evaluation of the presence of saliva secretion following the application of digital pressure. Saliva scintigraphy served as the objective test. Self-reported xerostomia was compared between the CSGS patients and a control group of patients who had undergone unilateral submandibular gland removal (USGR; n = 74). In the CSGS group, local recurrence occurred in 3.8% of the 80 cancer sites, and neck recurrence occurred in 5.9% of neck dissection sites. Regarding the subjective measurements, 7.0% of the CSGS patients reported xerostomia and 91.9% demonstrated saliva secretion by digital pressure. Scintigraphy revealed actively secreting glands, with 42.9% of them showing normal gland function; none of the patients had severe xerostomia. The relative risk of dry mouth was significantly higher in the USGR patients than in the CSGS patients (P < 0.001). Submandibular gland sparing during neck dissection was found to result in satisfactory saliva secretion, with a relatively small risk of local or neck recurrence.
Head and neck cancers are a heterogeneous group of tumors that are highly aggressive and collectively represent the sixth most common cancer worldwide. Ninety percent of head and neck cancers are ...squamous cell carcinomas (HNSCCs). The tumor microenvironment (TME) of HNSCCs consists of many different subsets of cells that infiltrate the tumors and interact with the tumor cells or with each other through various networks. Both innate and adaptive immune cells play a crucial role in mediating immune surveillance and controlling tumor growth. Here, we discuss the different subsets of immune cells and how they contribute to an immunosuppressive TME of HNSCCs. We also briefly summarize recent advances in immunotherapeutic approaches for HNSCC treatment. A better understanding of the multiple factors that play pivotal roles in HNSCC tumorigenesis and tumor progression may help define novel targets to develop more effective immunotherapies for patients with HNSCC.
Heat-shock protein 5 (HSPA5) is a marker for poor prognosis in breast cancer patients and has an important role in cancer progression, including promoting drug resistance and metastasis. In this ...study, we identify that the specific lysine residue 447 (K447) of HSPA5 could be modified with polyubiquitin for subsequent degradation through the ubiquitin proteasomal system, leading to the suppression of cell migration and invasion of breast cancer. We further found that GP78, an E3 ubiquitin ligase, interacted with the C-terminal region of HSPA5 and mediated HSPA5 ubiquitination and degradation. Knock down of GP78 significantly increased the expression of HSPA5 and enhanced migration/invasive ability of breast cancer cells. Knock down of histone deacetylase-6 (HDAC6) increased the acetylation of HSPA5 at lysine residues 353 (K353) and reduced GP78-mediated ubiquitination of HSPA5 at K447 and then increased cell migration/invasion. In addition, we demonstrate that E3 ubiquitin ligase GP78 preferentially binds to deacetylated HSPA5. Notably, the expression levels of GP78 inversely correlated with HSPA5 levels in breast cancer patients. Patients with low GP78 expression significantly correlated with invasiveness of breast cancer, advanced tumor stages and poor clinical outcome. Taken together, our results provide new mechanistic insights into the understanding that deacetylation of HSPA5 by HDAC6 facilitates GP78-mediated HSPA5 ubiquitination and suggest that post-translational regulation of HSPA5 protein is critical for HSPA5-mediated metastatic properties of breast cancer.
The most recent version of the European Society for Medical Oncology (ESMO) consensus guidelines for the treatment of patients with metastatic colorectal cancer (mCRC) was published in 2016, ...identifying both a more strategic approach to the administration of the available systemic therapy choices, and a greater emphasis on the use of ablative techniques, including surgery. At the 2016 ESMO Asia Meeting, in December 2016, it was decided by both ESMO and the Japanese Society of Medical Oncology (JSMO) to convene a special guidelines meeting, endorsed by both ESMO and JSMO, immediately after the JSMO 2017 Annual Meeting. The aim was to adapt the ESMO consensus guidelines to take into account the ethnic differences relating to the toxicity as well as other aspects of certain systemic treatments in patients of Asian ethnicity. These guidelines represent the consensus opinions reached by experts in the treatment of patients with mCRC identified by the Presidents of the oncological societies of Japan (JSMO), China (Chinese Society of Clinical Oncology), Korea (Korean Association for Clinical Oncology), Malaysia (Malaysian Oncological Society), Singapore (Singapore Society of Oncology) and Taiwan (Taiwan Oncology Society). The voting was based on scientific evidence and was independent of both the current treatment practices and the drug availability and reimbursement situations in the individual participating Asian countries.
Summary
This large cross-sectional study examined the associations of dietary intakes of total flavonoids and their subtypes with bone density in women and men. We found that greater flavonoid intake ...was associated with higher bone density in women but not in men.
Introduction
Studies in vitro and in animal models suggest a potential effect of flavonoids on bone health. Few studies have examined the association between the habitual intake of flavonoids and bone mineral density (BMD) in humans.
Methods
The cross-sectional study recruited 2,239 women and 1,078 men. A semiquantitative food frequency questionnaire was administered in face-to-face interviews to assess habitual dietary flavonoid intake using food composition databases. BMD was measured over the whole body (WB) and in the femoral neck (FN) and lumbar spine (LS) by dual-energy X-ray absorptiometry (DXA).
Results
After adjusting for covariates, women who consumed higher total flavonoids, and the subtypes of flavonols, flavan-3-ols, flavones, and proanthocyanidins tended to have greater BMD at the WB, LS, and FN (all P-trend < 0.05). Women in the highest (vs. the lowest) quartile of total flavonoids intake had 0.020 (1.91 %), 0.021 (2.51 %), and 0.013 (1.99 %) g/cm
2
greater BMD at the whole body, LS, and FN, respectively. For the subtypes of flavonoids, the corresponding differences in BMD (in g/cm
2
) were 0.012–0.021 (flavan-3-ols), 0.013–0.020 (flavonols), 0.016–0.019 (flavones), and 0.014–0.016 (proanthocyanidins), respectively. A higher intake of flavonones was associated with a greater BMD at the whole body (P-trend 0.041) and the FN (P-trend 0.022). In men, there were no significant positive associations between the consumption of total flavonoids and the subclasses and BMD at any sites.
Conclusion
Dietary flavonoids intake was positively associated with BMD in women. Further large studies are needed to clarify this issue in men.
The long-term outcome of 1390 children with acute lymphoblastic leukemia (ALL), treated in two successive clinical trials (Taiwan Pediatric Oncology Group (TPOG)-ALL-97 and TPOG-ALL-2002) between ...1997 and 2007, is reported. The event-free survival improved significantly (P=0.0004) over this period, 69.3+/-1.9% in 1997-2001 to 77.4+/-1.7% in 2002-2007. A randomized trial in TPOG-97 testing L-asparaginase versus epidoxorubicin in combination with vincristine and prednisolone for remission induction in standard-risk (SR; low-risk) patients yielded similar outcomes. Another randomized trial, in TPOG-2002, showed that for SR patients, two reinduction courses did not improve long-term outcome over one course. Decreasing use of prophylactic cranial irradiation in the period 1997-2008 was not associated with increased rates of CNS relapse, prompting complete omission of prophylactic cranial irradiation from TPOG protocols, beginning in 2009. Decreased use of etoposide and cranial irradiation likely contributed to the low incidence of second cancers. High-risk B-lineage ALL, T-cell, CD10 negativity, t(9;22), infant, and higher leukocyte count were consistently adverse factors, whereas hyperdiploidy >50 was a consistently favorable factor. Higher leukocyte count and t(9;22) retained prognostic significance in both TPOG-97 and TPOG-2002 by multivariate analysis. Although long-term outcome in TPOG clinical trials is comparable with results being reported worldwide, the persistent strength of certain prognostic variables and the lower frequencies of favorable outcome predictors, such as ETV6-RUNX1 and hyperdiploidy >50, in Taiwanese children warrant renewed effort to cure a higher proportion of patients while preserving their quality of life.
Data from clinical trials of human papillomavirus (HPV) vaccines showed that women naïve (negative for both type-specific antibodies and DNA) to vaccine types would derive benefit from vaccination; ...therefore, an understanding of the proportion of naïve women in different age groups is important for developing HPV vaccination strategies.
From November 2012 to April 2013, a total of 7372 healthy women aged 18–45 years were recruited in five provinces in China. Cervical specimens and serum samples were collected for each woman at entry. Cervical specimens were first tested by the HPV DNA enzyme immunoassay method; if positive, the specimens were then tested by reverse hybridization line probe assay and HPV-16 and HPV-18 specific polymerase chain reactions. Neutralizing antibodies against HPV-16 or HPV-18 were tested with a pseudovirion-based neutralization assay.
The overall prevalence of high-risk HPV DNA was 14.8% (1088/7367, 95% CI 14.0–15.6), and the seroprevalence of neutralizing antibodies against HPV-16 and HPV-18 was 12.6% (925/7367) and 4.9% (364/7367), respectively. In younger women (18–26 years) and middle-aged women (27–45 years), 83.8% (3116/3719) and 81.4% (2968/3648) were naïve to both HPV-16 and HPV-18 (both neutralizing antibodies and DNA were negative), respectively. In addition, 98.5% (3664/3719) and 98.0% (3575/3648) of the younger or middle-aged women were naïve to at least one HPV type (HPV-16 or HPV-18).
This study revealed that the majority of Chinese women aged 18–26 years and 27–45 years were naïve to both HPV-16 and HPV-18 and would thus derive full benefit from bivalent HPV vaccination.
The Tonga volcano eruption of 15 January 2022 unleashed a variety of atmospheric perturbations, coinciding with the recovery-phase of a geomagnetic storm. The ensuing thermospheric variations created ...rare display of extreme poleward-expanding conjugate plasma bubbles seen in the rate of total electron content index over 100–150°E, reaching ∼40°N geographic latitude. This is associated with fluctuations in FORMOSAT-7/COSMIC-2 (F7/C2) ion-density measurements and spread-F in ionograms. Preceding to this, an unusually strong pre-reversal enhancement (PRE) occurred in the global ionospheric specification (GIS) electron density profiles derived from F7/C2 observations. The GIS also revealed a decrease of equatorial ionization anomaly (EIA) crest density due to the storm impact. Reduced E-region conductivity by volcano-induced waves and enhanced F-region wind, further accelerated by reduced ion-drag over the EIA, apparently intensified the PRE.
Accompanied with the strong PRE, volcano-induced seed perturbations triggered the super plasma bubble activity.
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