This study aimed to compare the quality of life (QOL), psychosocial status, sexual function, and menopausal symptoms between the risk-reducing salpingo-oophorectomy (RRSO) and non-RRSO groups ...comprising BRCA mutation carriers and to evaluate the effect of timing of RRSO on those aspects.
This cross-sectional study recruited BRCA mutation carriers aged ≥35 years between September 2015 and September 2016. Demographic data of carriers were collected. Outcomes were measured using the questionnaires addressing QOL, anxiety, depression, optimism, sexual function, and menopausal symptoms.
Of 52 participants, 30 (57.7%) underwent RRSO, whereas 22 (42.3%) did not. In the RRSO group, 16 (53.3%) and 14 (46.7%) women underwent RRSO before and after menopause, respectively. The mean age in the RRSO group was higher than that in the non-RRSO group (49.8 vs. 42.1 years, respectively, p = 0.002). The scores for QOL, anxiety, depression, optimism, sexual function, and menopausal symptoms were similar between both groups. In the multivariate analysis, RRSO uptake was associated with worse physical QOL (coefficient, −5.350; 95% confidence interval, −10.593 to −0.108). With respect to the timing of RRSO, only the mental QOL was significantly lower in the postmenopausal RRSO group than in the premenopausal RRSO group (39.2 vs. 43.7, respectively, p = 0.043).
We could not find any difference in mental QOL, psychosocial status, sexual function, and menopausal symptoms between the RRSO and non-RRSO groups. RRSO uptake only affected worse physical QOL. These results will help physicians counsel BRCA mutation carriers about the effect of RRSO on QOL.
Variants in the
gene region may explain ethnic differences in the association of Alzheimer's disease (AD) with ε4. Ethnic differences in allele frequencies for three
region SNPs (single nucleotide ...polymorphisms) were identified and tested for association in 19,398 East Asians (EastA), including Koreans and Japanese, 15,836 European ancestry (EuroA) individuals, and 4985 African Americans, and with brain imaging measures of cortical atrophy in sub-samples of Koreans and EuroAs. Among ε4/ε4 individuals, AD risk increased substantially in a dose-dependent manner with the number of
promoter SNP rs405509
alleles in EastAs
: OR (odds ratio) = 27.02,
= 8.80 × 10
;
: OR = 15.87,
= 2.62 × 10
) and EuroAs (
: OR = 18.13,
= 2.69 × 10
;
: OR = 12.63,
= 3.44 × 10
), and rs405509-
homozygotes had a younger onset and more severe cortical atrophy than those with
-allele. Functional experiments using
promoter fragments demonstrated that
lowered
expression in human brain and serum. The modifying effect of rs405509 genotype explained much of the ethnic variability in the AD/ε4 association, and increasing
expression might lower AD risk among ε4 homozygotes.
Stress that impairs endoplasmic reticulum (ER) function leads to an accumulation of unfolded or misfolded proteins in the ER (ER stress). Autophagy is a lysosomal pathway involved in the turnover of ...cellular macromolecules and organelles, which emerging data indicate that ER stress is also a potent inducer of autophagy. ER stress and autophagy are involved in human cancer. We examined the expression of ER stress‐related proteins GRP78 and C/EBP homologous protein (CHOP) and autophagic proteins (Beclin‐1 and LC3) in non‐small cell lung carcinomas (NSCLCs), bronchioloalveolar carcinomas (BACs) and atypical adenomatous hyperplasias (AAHs) to understand their role in the NSCLC pathogenesis. The expression of GRP78 and CHOP, Beclin‐1 and LC3 were analyzed using immunohistochemistry on tissue sections from 133 NSCLC (69 squamous cell carcinomas, 56 adenocarcinomas (AC) and eight other NSCLCs), 21 BAC and 9 AAH. Expression of GRP78 and Beclin‐1 was correlated with low tumor stage (p < 0.001 and p = 0.019, respectively) and longer survival (p = 0.007 and p <0.001, respectively) by Kaplan–Meier analysis. However, CHOP was correlated with high tumor stage (p = 0.038) and shorter survival (p = 0.012). Expression of GRP78 and Beclin‐1 was positively correlated (p = 0.006). Our study showed that the expression of GRP78, CHOP, Beclin‐1 and LC3 in lung cancer and its relation with clinicopathologic factors and patients survival. These results suggest that GRP78, CHOP and Beclin‐1 may play an important role in tumorigenesis of lung AC and may serve as new prognostic indicators for outcome of the patients with NSCLC.
An 8.5-Gb/s/pin (Gb/s) 12-Gb LPDDR5 SDRAM is implemented in a second-generation 10-nm DRAM process with a hybrid-bank architecture that provides a power-optimized bank solution depending on the bank ...modes (4B/4BG, 16B-merged bank, 8B-split bank). Based on the specified bank modes, vertical and horizontal skew-cancel schemes for high density and an RBUS-based DBI ac to minimize data transition are newly proposed. Thus, the switching power of RBUS DBI ac is saved by 8.9% compared to that of DBI ac "OFF." To improve the rank interleaving efficiency with a current increase, partially enabled WCK (PE-WCK) mode is proposed, which minimizes the number of enabled circuits for maintaining the WCK2CK synchronization. Therefore, the current can be saved by 62% without a timing constraint compared to the WCK always-ON mode. To achieve high-speed operation beyond 6.4 Gb/s, speed-boosting techniques, namely, the two-step duty corrector, active resonant load (ARL), and one-tap decision feedback equalizer (DFE) with offset calibration, are newly adopted. In the coarse step in the two-step duty corrector, the value of the duty error decreases to below 5% by suppressing the dc signal. In the fine step, the remaining duty error is further reduced within 2.5 ps by the duty cycle monitor (DCM) and duty cycle adjustor (DCA). Moreover, the skew increase beyond 6.4 Gb/s due to the bandwidth limit by the heavy loading of four-phase WCK signals is alleviated by the ARL, where the four-phase skew is within 5 ps irrespective of process, voltage, and temperature (PVT) variations. The direct feedback DFE enables fast feedback (< 118 ps) for tap coefficient control, and offset calibration reduces the three-sigma offset of the four dynamic latches in DQ within 5 mV.
Recent studies using stereotactic body radiotherapy (SBRT) for hepatocellular carcinoma (HCC) have reported high tumor response and local control. However, the optimal SBRT dose remains unknown, and ...it is still not clear whether a dose response relationship for local control (LC) and overall survival (OS) exist or not. We performed this study to determine whether a dose response relationship for LC and OS is observed in SBRT for inoperable HCC.
Between 2003 and 2011, 108 patients with HCC were treated with SBRT. All patients were unsuitable for surgery or local ablation and had incomplete response to transarterial chemoembolization. Eighty-two patients with a longest tumor diameter (LD) less than or equal to 7.0 cm who were treated with 3-fraction SBRT and were analyzed. This cohort comprised 74 Child-Turcotte-Pugh (CTP) class A patients and 8 CTP class B7 patients. The median LD was 3.0 cm (range, 1.0-7.0 cm), and the median dose was 51 Gy (range, 33-60 Gy).
LC and OS rates at 2 years after SBRT were 87% and 63%, respectively, with a median follow-up duration of 30 months for all patients. The 2-year LC/OS rates for patients treated with doses of > 54, 45-54, and < 45 Gy were 100/71, 78/64, and 64%/30%, respectively (p = .009/p < .001). Multivariate analysis revealed that the SBRT dose (p = .005) and Barcelona Clinic Liver Cancer stage (p = .015) were significant prognostic factors for OS. Correlation analysis revealed a positive linear relationship between the SBRT dose and LC (p = .006, R = .899)/OS (p = .002, R = .940) at 2 years. Based on the tumor-control probability model, a dose of 54.8 Gy provides 2-year LC with a 90% probability. Five patients experienced grade 3 or higher gastrointestinal toxicity, and 6 had deteriorating of CTP score by greater than or equal to 2 within 3 months of SBRT.
This study demonstrated a dose response relationship for LC and OS with SBRT for HCC. Higher LC rates resulting from an increased dose may translate into survival benefits for patients with HCC.
The association between acute pancreatitis (AP) and gastrointestinal cancers in diabetic patients is currently not well understood. The study aim was to investigate the association between AP and ...gastrointestinal cancers in diabetic patients. Data from the Korean National Health Insurance Service database were analyzed. Participants with diabetes who underwent a health examination between 2009 and 2012 were followed up till December 2018. The primary outcome was the occurrence of gastrointestinal cancer. A total of 2,263,184 patients were included in the final analysis. Patients with a history of AP (
= 2390) were found to have a significantly higher risk of gastrointestinal cancer, except for esophageal cancer, as follows: gastric cancer (aHR = 1.637, 95% CI: 1.323-2.025), colorectal cancer (aHR = 2.183, 95% CI: 1.899-2.51), liver cancer (aHR = 2.216, 95% CI: 1.874-2.621), pancreatic cancer (aHR = 4.558, 95% CI: 4.078-5.095), bile duct cancer (aHR = 3.996, 95% CI: 3.091-5.269), and gallbladder cancer (aHR = 2.445, 95% CI: 1.459-4.099). The history of AP is associated with the increased risk of gastrointestinal cancer in diabetic patients. It is necessary to investigate the history of AP and more actively recommend screening for gastrointestinal cancers in such patients.
Despite considerable development in the field of single‐atom catalysts (SACs) on carbon‐based materials, the reported strategies for synthesizing SACs generally rely on top‐down approaches, which ...hinder achieving both simple and universal synthesis routes that are simultaneously applicable to various metals and nanocarbons. Here, a universal strategy for fabricating nanocarbon based‐SACs using a flash bottom‐up arc discharge method to mitigate these issues is reported. The ionization of elements and their recombination process during arc discharge allows the simultaneous incorporation of single metal atoms (Mn, Fe, Co, Ni, and Pt) into the crystalline carbon lattice during the formation of carbon nanohorns (CNHs) and N‐doped arc graphene. The coordination environment around the Co atoms of Co1/CNH can be modulated by a mild post‐treatment with NH3. As a result, Co1/CNH exhibits good oxygen reduction reaction activity, showing a 1.92 times higher kinetic current density value than the commercial Pt/C catalyst in alkaline media. In a single cell experiment, Co1/CNH exhibits the highest maximum power density of 472 mW cm−2 compared to previously reported nonprecious metal‐based SACs.
The authors report a universal strategy for fabricating single‐atom catalysts (SACs) using a flash bottom‐up arc discharge. It allows the simultaneous incorporation of metal atoms into the carbon lattice during the formation of nanocarbons. It is applicable to various metals and nanocarbons. In a single cell experiment, Co1/CNH catalysts exhibit the highest maximum power density compared to reported nonprecious metal‐based SACs.
Abstract
The medial prefrontal cortex (mPFC) and the lateral habenula (LHb) play roles in drug addiction and cognitive functions. Our previous studies have suggested that acupuncture at
Shenmen
(HT7) ...points modulates mesolimbic reward system in order to suppress drug‐induced addiction behaviours. To explore whether an mPFC‐LHb circuit mediates the inhibitory effects of acupuncture on addictive behaviours, we examined the projection from mPFC to LHb, excitation of mPFC neurons during acupuncture stimulation, the effects of optogenetic modulation of mPFC‐LHb on HT7 inhibition of cocaine‐induced locomotion and the effect of mPFC lesion on HT7 inhibition of nucleus accumbens (NAc) dopamine release. Acupuncture was applied at bilateral HT7 points for 20 s, and locomotor activity was measured in male Sprague–Dawley rats. Although cocaine injection significantly increased locomotor activity, HT7 acupuncture suppressed the cocaine‐induced locomotion. The inhibitory effect of HT7 on cocaine‐enhanced locomotion was blocked by optogenetic silencing of the mPFC‐LHb circuit. In vivo extracellular recordings showed that HT7 acupuncture evoked an increase in the action potentials of mPFC neurons. Optopatch experiment proved glutamatergic projections from mPFC to LHb. HT7 acupuncture suppressed NAc dopamine release following cocaine injection, which was blocked by electrolytic lesion of mPFC. These results suggest the mediation of mPFC‐LHb circuit in the inhibitory effects of acupuncture on cocaine psychomotor activity in rats.
The treatment decisions for patients with hepatocellular carcinoma are determined by a wide range of factors, and there is a significant difference between the recommendations of widely used staging ...systems and the actual initial treatment choices. Herein, we propose a machine learning-based clinical decision support system suitable for use in multi-center settings. We collected data from nine institutions in South Korea for training and validation datasets. The internal and external datasets included 935 and 1750 patients, respectively. We developed a model with 20 clinical variables consisting of two stages: the first stage which recommends initial treatment using an ensemble voting machine, and the second stage, which predicts post-treatment survival using a random survival forest algorithm. We derived the first and second treatment options from the results with the highest and the second-highest probabilities given by the ensemble model and predicted their post-treatment survival. When only the first treatment option was accepted, the mean accuracy of treatment recommendation in the internal and external datasets was 67.27% and 55.34%, respectively. The accuracy increased to 87.27% and 86.06%, respectively, when the second option was included as the correct answer. Harrell's C index, integrated time-dependent AUC curve, and integrated Brier score of survival prediction in the internal and external datasets were 0.8381 and 0.7767, 91.89 and 86.48, 0.12, and 0.14, respectively. The proposed system can assist physicians by providing data-driven predictions for reference from other larger institutions or other physicians within the same institution when making treatment decisions.
Introduction
Knowledge on the learning curve for the repair of Achilles tendon rupture is limited. The aim of this study was to quantify the learning curve for the Krackow suture technique for the ...repair of Achilles tendon rupture and to identify the correlation between the cumulative volume of cases and clinical outcome measures.
Materials and methods
A total of 226 cases of Achilles tendon repair using the Krackow suture technique were reviewed. Each surgery was independently performed by four surgeons who started a foot and ankle specialty career after fellowship training. After logarithmic transformation of the operative time and cumulative volume of cases, a linear regression analysis was performed to determine the best-fit linear equations to predict the required time for the Krackow suture technique according to the cumulative volume of cases. The correlation between the cumulative volume of cases and clinical outcome measures was analyzed using Pearson correlation coefficients. Receiver operating characteristic curves were constructed to determine the minimum number of cases with an operative time shorter than the average in the first 30 cases.
Results
In all four surgeons, significant log-linear correlations were observed between the operative time and cumulative volume of cases. The best-fit linear equations showed estimated learning rates of 90%, 87%, 92%, and 86% for each of the four surgeons, indicating that the necessary operative time decreased by 10%, 13%, 8%, and 14%, respectively, when the cumulative volume of cases had doubled. The minimum number of cases with an operative time shorter than the average was 9 (91% sensitivity and 59% specificity). The clinical outcome measures at 6 and 12 months postoperatively were available for one surgeon; however, no correlation was found with the cumulative volume of cases.
Conclusion
The learning rate for the Krackow suture technique for the repair of Achilles tendon rupture was approximately 89%, indicating that the required operative time can decrease by up to 11% when the cumulative volume of cases doubles. Therefore, it is important to rapidly accumulate surgical experience during the early phase of training.
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