Background: Combined therapy with tyrosine kinase inhibitors (TKIs) and anti-PD-1 antibodies has shown high tumor response rates for patients with unresectable hepatocellular carcinoma (HCC). ...However, using this treatment strategy to convert initially unresectable HCC to resectable HCC was not reported. Methods: Consecutive patients with unresectable HCC who received first-line therapy with combined TKI/anti-PD-1 antibodies were analyzed. Tumor response and resectability were evaluated via imaging every 2 months (±2 weeks) using RECIST v1.1. Resectability criteria were (1) R0 resection could be achieved with sufficient remnant liver volume and function; (2) intrahepatic lesions were evaluated as partial responses or stable disease for at least 2 months; (3) no severe or persistent adverse effects occurred; and (4) hepatectomy was not contraindicated. Results: Sixty-three consecutive patients were enrolled. Of them, 10 (15.9%) underwent R0 resection in 3.2 months (range: 2.4–8.3 months) after the initiation of combination therapy. At baseline, these 10 patients had a median largest tumor diameter of 9.3 cm, 7 had Barcelona Clinic Liver Cancer stage C (vascular invasion) disease, 2 had stage B, and 1 had stage A. Before surgery, 6 patients were evaluated as a partial response, 3 stable disease, and 1 partial response in the intrahepatic lesion but a new metastatic lesion in the right adrenal gland. Six patients (60%) achieved a pathological complete response. One patient died from immune-related adverse effects 2.4 months after hepatectomy. After a median follow-up of 11.2 months (range: 7.8–15.9 months) for other 9 patients, 8 survived without disease recurrence, and 1 experienced tumor recurrence. Conclusions: Combination of TKI/anti-PD-1 antibodies is a feasible conversion therapy for patients with unresectable HCC to become resectable. This study represents the largest patient cohort on downstaging role of combinational systemic therapy on TKI and PD-1 antibody for HCC.
Background: Neurofibromatosis type 1 (NF1), a genetic tumor predisposition syndrome that affects about 1 in 3000 newborns, is caused by mutations in the NF1 gene and subsequent inactivation of its ...encoded neurofibromin. Neurofibromin is a tumor suppressor protein involved in the downregulation of Ras signaling. Despite a diverse clinical spectrum, one of several hallmarks of NF1 is a peripheral nerve sheath tumor (PNST), which comprises mixed nervous and fibrous components. The distinct spatiotemporal characteristics of plexiform and cutaneous neurofibromas have prompted hypotheses about the origin and developmental features of these tumors, involving various cellular transition processes. Methods: We retrieved published literature from PubMed, EMBASE, and Web of Science up to 21 June 2022 and searched references cited in the selected studies to identify other relevant papers. Original articles reporting the pathogenesis of PNSTs during development were included in this review. We highlighted the Schwann cell (SC) lineage shift to better present the evolution of its corresponding cellular origin hypothesis and its important effects on the progression and malignant transformation of neurofibromas. Conclusions: In this review, we summarized the vast array of evidence obtained on the full range of neurofibroma development based on cellular and molecular pathogenesis. By integrating findings relating to tumor formation, growth, and malignancy, we hope to reveal the role of SC lineage shift as well as the combined impact of additional determinants in the natural history of PNSTs.
Nowadays, laser is the mainstay treatment for cafe-au-lait macules (CALMs), but no systematic review has been published to demonstrate the overall efficacy and it's still controversial which type of ...laser is optimal. Thus, we conduct the meta-analysis to evaluate the effectiveness and side effects of various types of lasers in treating CALMs. Original articles reporting the efficacy and side effects for CALMs in laser treatment were identified in PubMed, EMBASE, and Web of Science from 1983 to April 11, 2023. Using R software and the 'meta' package, meta-analysis was conducted for clearance and recurrence for evaluation of efficacy. And the occurrence of hypopigmentation and hyperpigmentation rate was pooled for safety evaluation. We used RoB2 and ROBINS-I tools to assess the risks of bias in RCT studies and non-RCT studies, respectively. The Grading of Recommendations, Assessment, Development and Evaluation system was used to assess the quality of the evidence. Nineteen studies involving 991 patients were included, which had a very low to moderate quality of evidence. The pooled 75% clearance rate was 43.3% (95% CI 31.8-54.7%, I
= 96%), 50% clearance rate was 75% (95% CI 62.2-85.9%, I
= 89%) and the recurrence rate was 13% (95% CI 3.2-26.5%, I
= 88%). The pooled hypopigmentation and hyperpigmentation rates were 1.2% (95% CI 0.3-2.1%, I
= 0%) and 1.2% (95% CI 0.3-2%, I
= 0%), respectively. Subgroup analysis revealed that QS-1064-nm Nd:YAG laser treatment not only achieved more than 75% clearance rate in 50.9% of patients (95% CI 26.9-74.4%, I
= 90%) but also resulted in the lowest hypopigmentation and hyperpigmentation rate of 0.5% (95% CI 0.0-2.5%, I
= 26%) and 0.4% (95% CI 0.0-2.5%, I
= 0%). To draw a conclusion, the laser treatment could reach an overall clearance rate of 50% for 75% of the patients with CALMs, for 43.3% of the patients, the clearance rate could reach 75%. When looking at different wavelength subgroups, QS-1064-nm Nd:YAG laser exhibited the best treatment capability. Laser of all the wavelength subgroups presented acceptable safety regarding of the low occurrence of side effects, namely, hypopigmentation and hyperpigmentation.
The high-speed multimode optical interconnects based on vertical-cavity surface-emitting laser and multimode fiber (MMF) are severely constrained by band-limited devices, modulation nonlinearity, and ...laser induced noises such as relative intensity noise, mode partition noise, and fiber-induced noises such as chromatic dispersion and mode dispersion. The advanced digital signal processing technologies have been viewed as the inevitable tool to mitigate the physical limitations of electrical and optical components and the noise interactions during the transmission. In order to achieve multimode 100 Gbps/lane over 100-m transmission with the existing devices, a Volterra equalizer has been proven as a very effective equalization solution to deal with nonlinear impairments. However, the practical implementation of this nonlinear equalizer has been constrained by its tremendously high computation complexity. In this paper, we propose the threshold-based pruned retraining Volterra equalization (TRVE) to reduce the computation complexity, while maintaining the transmission performance. Multimode 100-Gbps/lane transmission over 100-m OM3 MMF has been experimentally demonstrated with up to 70.7% computation complexity reduction, while keeping the bit error rate under the 7% hard-decision forward error correction limit. In addition, the TRVE with l 1 -regularization is also proposed and experimentally verified to optimize the threshold selection.
Lycopene (LYC) is a potent antioxidant synthesized by red vegetables or plants. Di-2-ethylhexyl phthalate (DEHP) is frequently detected in diverse agricultural environments and considered as a ...reproductive toxicant. The present research was designed to assess the potential mechanisms of DEHP-induced testicular toxicity and the treatment efficacy of LYC. In this study, after the oral administration of LYC at the dose of 5 mg per kg b.w. per day, mice were given 500 or 1000 mg per kg b.w. per day of DEHP. This research suggested that LYC prevented the DEHP-induced disorder at the levels of activity and content of CYP450 enzymes. LYC attenuated DEHP-caused enhancement in nuclear xenobiotic receptors (NXRs) and the phase I metabolizing enzymes (CYP1, CYP2, CYP3,
) levels. Furthermore, endoplasmic reticulum (ER) stress was induced by DEHP and triggered unfolded protein response (UPR). Interestingly, LYC could effectively ameliorate these "hit". The present study suggested that LYC prevents DEHP-induced ER stress in testis
regulating NXRs and UPR
.
The catalytic hydrogenation of carbon dioxide and bicarbonate to formate has been explored extensively. The vast majority of the known active catalyst systems are based on precious metals. Herein, we ...describe an effective, phosphine‐free, air‐ and moisture‐tolerant catalyst system based on Knölker’s iron complex for the hydrogenation of bicarbonate and carbon dioxide to formate. The catalyst system can hydrogenate bicarbonate at remarkably low hydrogen pressures (1–5 bar).
Carbon dioxide is an attractive C1 source because it is easily and abundantly available, relatively nontoxic, and renewable. An effective, phosphine‐free, air‐ and moisture‐tolerant catalyst system based on Knölker's iron complex for the hydrogenation of bicarbonate and carbon dioxide to formate is described. The catalyst system hydrogenates bicarbonate at remarkably low hydrogen pressures.
Most previous works on saliency detection are dedicated to 2D images. Recently it has been shown that 3D visual information supplies a powerful cue for saliency analysis. In this paper, we propose a ...novel saliency method that works on depth images based on anisotropic center-surround difference. Instead of depending on absolute depth, we measure the saliency of a point by how much it outstands from surroundings, which takes the global depth structure into consideration. Besides, two common priors based on depth and location are used for refinement. The proposed method works within a complexity of O(N) and the evaluation on a dataset of over 1000 stereo images shows that our method outperforms state-of-the-art.
The Veterans Affairs Diabetes Trial previously showed that intensive glucose lowering, as compared with standard therapy, did not significantly reduce the rate of major cardiovascular events among ...1791 military veterans (median follow-up, 5.6 years). We report the extended follow-up of the study participants.
After the conclusion of the clinical trial, we followed participants, using central databases to identify procedures, hospitalizations, and deaths (complete cohort, with follow-up data for 92.4% of participants). Most participants agreed to additional data collection by means of annual surveys and periodic chart reviews (survey cohort, with 77.7% follow-up). The primary outcome was the time to the first major cardiovascular event (heart attack, stroke, new or worsening congestive heart failure, amputation for ischemic gangrene, or cardiovascular-related death). Secondary outcomes were cardiovascular mortality and all-cause mortality.
The difference in glycated hemoglobin levels between the intensive-therapy group and the standard-therapy group averaged 1.5 percentage points during the trial (median level, 6.9% vs. 8.4%) and declined to 0.2 to 0.3 percentage points by 3 years after the trial ended. Over a median follow-up of 9.8 years, the intensive-therapy group had a significantly lower risk of the primary outcome than did the standard-therapy group (hazard ratio, 0.83; 95% confidence interval CI, 0.70 to 0.99; P=0.04), with an absolute reduction in risk of 8.6 major cardiovascular events per 1000 person-years, but did not have reduced cardiovascular mortality (hazard ratio, 0.88; 95% CI, 0.64 to 1.20; P=0.42). No reduction in total mortality was evident (hazard ratio in the intensive-therapy group, 1.05; 95% CI, 0.89 to 1.25; P=0.54; median follow-up, 11.8 years).
After nearly 10 years of follow-up, patients with type 2 diabetes who had been randomly assigned to intensive glucose control for 5.6 years had 8.6 fewer major cardiovascular events per 1000 person-years than those assigned to standard therapy, but no improvement was seen in the rate of overall survival. (Funded by the VA Cooperative Studies Program and others; VADT ClinicalTrials.gov number, NCT00032487.).
BACKGROUND/OBJECTIVES
To obtain national and regional estimates of prevalence of frailty with or without cognitive impairment, and cognitive impairment with or without frailty among older adults in ...the United States, and to identify profiles of characteristics that distinguish their joint versus separate occurrence.
DESIGN
Cross‐sectional.
SETTING
Community or non–nursing home residential care settings.
PARTICIPANTS
A U.S. nationally representative sample of 7,497 older adults aged 65 and older from the National Health and Aging Trends Study.
MEASUREMENTS
Frailty was measured by the physical frailty phenotype. Cognitive impairment was assessed by cognitive performance testing of executive function and memory or by proxy reports. Multinomial logistic regression was used to identify profiles of demographic, socioeconomic, health, behavioral, and psychosocial characteristics that distinguish four subgroups: not‐frail and cognitively intact (“neither”), not‐frail and cognitively impaired (“Cog. only”), frail and cognitively intact (“frailty only”), and frail and cognitively impaired (“both”).
RESULTS
The prevalence of “Cog. only,” “frailty only,” and “both” was 25.5%, 5.6%, and 8.7%, respectively. Individuals with“frailty only” had the highest prevalence of obesity, current smoking, comorbidity, lung disease, and history of surgery. The “both” group had the highest prevalence of dementia, depression, cardiovascular diseases, and disability. No significant differences were found between the “Cog. only” group and the “neither” group with respect to history of surgery and comorbidity burden. The prevalence of dementia in the “Cog. only” was less than half of that in the “both” group.
CONCLUSION
The finding of sizable subgroups having physical frailty but not cognitive impairment, and vice versa, suggests that the two cannot be considered necessarily as antecedent or sequela of one another. The study provided empirical data supporting the prioritization of comorbidity, obesity, surgery history, and smoking status in clinical screening of frailty and cognitive impairment before formal diagnostic assessments.
The neutrophil-to-lymphocyte ratio (NLR) is a useful biomarker that reflects systemic inflammation responses. However, the prognostic value of the NLR in patients with primary liver cancer (PLC) ...remains controversial. We performed a meta-analysis of 26 studies (comprising 4,461 patients) to evaluate the association between the pre-treatment NLR and clinical outcomes of overall survival (OS) and disease-free survival (DFS) in patients with PLC. The correlation between NLR and tumor characteristics or other inflammation-related parameters was also assessed. Data were synthesized using the random-effects model of DerSimonian and Laird, and the hazard ratio (HR) or odds ratio (OR) with 95% confidence interval (CI) was used to estimate effect size. Our analysis indicated that a high NLR predicted poor OS (HR, 2.102; 95% CI: 1.741-2.538) and DFS (HR, 2.474; 95% CI: 1.855-3.300) for PLC. A high NLR was associated with the presence of tumor vascular invasion (OR: 1.889, 95% CI: 1.487-2.400; p<0.001) and an elevated alpha-fetoprotein level (OR: 1.536; 95% CI: 1.152-2.048; p = 0.003). Thus, we conclude that a high NLR indicates a poor prognosis for patients with PLC and may also be predictive for PLC invasion and metastasis. Subgroup analysis suggested that the predictive role of NLR in cholangiocarcinoma is limited, and a further large study to confirm these findings is warranted.
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