pH Mapping of Gliomas Using Quantitative Chemical Exchange Saturation Transfer MRI: Quasi-Steady-State, Spillover-, and MT-Corrected Omega Plot Analysis.

BACKGROUND: Quantitative in-situ pH mapping of gliomas is important for therapeutic interventions, given its significant association with tumor progression, invasion, and metastasis. Although chemical exchange saturation transfer (CEST) offers a noninvasive way for pH imaging based on the pH-dependent exchange rate (ksw ), the reliable quantification of ksw in glioma remains constrained due to technical challenges. PURPOSE: To quantify the pH of gliomas by measuring the proton exchange rate through optimized omega plot analysis. STUDY TYPE: Prospective. PHANTOMS/ANIMAL MODEL/SUBJECTS: Creatine and murine brain lysates phantoms, six rats with glioma xenograft model, and three patients with World Health Organization grade 2-4 gliomas. FIELD STRENGTH/SEQUENCE: 11.7 T, 7.0 T, CEST imaging, T2 -weighted (T2 W) imaging, and T1 -mapping. ASSESSMENT: Omega plot analysis, quasi-steady-state (QUASS) analysis, multi-pool Lorentzian fitting, amine and amide concentration-independent detection, pH enhanced method with the combination of amide and guanidyl (pHenh ), and magnetization transfer ratio (MTR) were utilized for pH metric quantification. The clinical outcomes were determined through radiologic follow-up and histopathological analysis. STATISTICAL TESTS: Mann-Whitney U test was performed to compare glioma with normal tissue, and Pearson's correlation analysis was used to assess the relationship between ksw and other parameters. RESULTS: In vitro experiments reveal that the determined ksw at 2 ppm increases exponentially with pH (creatine phantoms: ksw = 106 + 0.147 × 10(pH-4.198) ; lysates: ksw = 185.1 + 0.101 × 10(pH-3.914) ). Omega plot analysis exhibits a linear correlation between 1/MTRRex and 1/ω1 2 in the glioma xenografts (R2 > 0.98) and glioma patients (R2 > 0.99). The exchange rate in the rat glioma decreases compared to the contralateral normal tissue (349.46 ± 30.40 s-1 vs. 403.54 ± 51.01 s-1 , P = 0.025), while keeping independence from changes in concentration (r = 0.5037, P = 0.095). Similar pattern was observed in human data. DATA CONCLUSION: Utilizing QUASS-based, spillover-, and MT-corrected omega plot analysis for the measurement of exchange rates, offers a feasible method for quantifying pH within glioma. LEVEL OF EVIDENCE: NA TECHNICAL EFFICACY: Stage 1.

Tilavonemab in early Alzheimer's disease: results from a phase 2, randomized, double-blind study.

Tau accumulation in patients with Alzheimer's disease tracks closely with cognitive decline and plays a role in the later stages of disease progression. This phase 2 study evaluated the safety and efficacy of tilavonemab, an anti-tau monoclonal antibody, in patients with early Alzheimer's disease. In this 96-week, randomized, double-blind, placebo-controlled study (NCT02880956), patients aged 55-85 years meeting clinical criteria for early Alzheimer's disease with a Clinical Dementia Rating-Global Score of 0.5, a Mini-Mental State Examination score of 22 to 30, a Repeatable Battery for the Assessment of Neuropsychological Status-Delayed Memory Index score of ≤85, and a positive amyloid PET scan were randomized 1:1:1:1 to receive one of three doses of tilavonemab (300 mg, 1000 mg, or 2000 mg) or placebo via intravenous infusion every 4 weeks. The primary end point was the change from baseline up to Week 96 in the Clinical Dementia Rating-Sum of Boxes (CDR-SB) score. Safety evaluations included adverse event monitoring and MRI assessments. A total of 453 patients were randomized, of whom 337 were treated with tilavonemab (300 mg, n = 108; 1000 mg, n = 116; 2000 mg, n = 113) and 116 received placebo. Baseline demographics and disease characteristics were comparable across groups. The mean age was 71.3 (SD 7.0) years, 51.7% were female, and 96.5% were White. At baseline, the mean CDR-SB score was 3.0 (1.2), which worsened through Week 96 for all treatment groups. The least squares mean change from baseline at Week 96 in the CDR-SB score with tilavonemab was not significantly different compared with placebo [300 mg (n = 85): -0.07 (95% confidence interval, CI: -0.83 to 0.69); 1000 mg (n = 91): -0.06 (95% CI: -0.81 to 0.68); 2000 mg (n = 81): 0.16 (95% CI: -0.60 to 0.93); all P ≥ 0.05]. The incidence of any adverse event and MRI findings were generally comparable across groups. Tilavonemab was generally well tolerated but did not demonstrate efficacy in treating patients with early Alzheimer's disease. Further investigations of tilavonemab in early Alzheimer's disease are not warranted.

Mesenchymal stem cells inhibit MRP-8/14 expression and neutrophil migration via TSG-6 in the treatment of lupus nephritis.

Abnormal infiltration and activation of neutrophils play a pathogenic role in the development of lupus nephritis (LN). Myeloid-related proteins (MRPs), MRP-8 and -14, also known as the damage-associated molecular patterns (DAMPs), are mainly secreted by activated neutrophils in systemic lupus erythematosus (SLE). Mesenchymal stem cells (MSCs) regulate a variety of immune cells to treat LN, but it is not clear whether MSCs can regulate neutrophils and the expression of MRP-8/14 in LN. Here, we demonstrated that neutrophil infiltration and MRP-8/14 expression were increased in the kidney of MRL/lpr mice and both decreased after MSCs transplantation. Further, the results showed that tumor necrosis factor- (TNF) stimulated gene-6 (TSG-6) in MSCs is necessary for MSCs to inhibit MRP-8/14 expression in neutrophils and neutrophil migration. In addition, small-molecule immunosuppressant had no significant effect on the expression of MRP-8/14 in neutrophils. Therefore, our results suggest that MSCs inhibited MRP-8/14 expression and neutrophil migration by secreting TSG-6 in the treatment of LN.

Node-downloadable frequency transfer system based on a mode-locked laser with over 100 km of fiber.

To meet the requirements of time-frequency networks and enable frequency downloadability for nodes along the link, we demonstrated the extraction of stable frequency signals at nodes using a mode-locked laser under the condition of 100 km laboratory fiber. The node consists of a simple structure that utilizes widely used optoelectronic devices and enables plug-and-play applications. In addition, the node can recover frequency signals with multiple frequencies, which are useful for scenarios that require different frequencies. Here, we experimentally demonstrated a short-term frequency instability of 2.83 × 10-13@1 s and a long-term frequency instability of 1.18 × 10-15@10,000 s at the node, which is similar to that at the remote site of the frequency transfer system. At the same time, frequency signals with different frequencies also achieved stable extraction with the same performance at the node. Our results can support the distributed application under large-scale time-frequency networks.

CD56brightCD16- to CD57+CD56dimCD16+ NK cell ratio discriminates disease activity and renal involvement in patients with systemic lupus erythematosus.

OBJECTIVES: We aimed to discriminate subpopulations of peripheral natural killer (NK) cells of patients with systemic lupus erythematosus (SLE) and evaluate their usability in monitoring disease activity. METHODS: The total number of NK cells and their subpopulations were determined by flow cytometry in 68 patients with SLE and 35 healthy controls. Clinical data were extracted from medical records, including serum anti-double-stranded-DNA (anti-dsDNA), complement C3 and C4, and urine protein. Disease activity in patients with SLE was assessed using the SLE Disease Activity Index-2000 (SLEDAI-2K). RESULTS: The percentages and absolute numbers of NK cells decreased, and the proportions of three major NK cell subsets defined by cell maturation status altered in SLE patients. The frequency of CD56brightCD16- NK (immature, Im NK) cells increased, while that of the CD57+CD56dimCD16- subset (mature, more differentiated, MD NK) decreased in patients with high-activity SLE, resulting in a significant increase in the Im NK-to-MD NK ratio as compared with that in patients with low-activity SLE. The area under the receiver operating characteristic curve indicated that the ratio was 0.722 in severe SLE and 0.773 in lupus nephritis, with optimal cut-off levels of 0.075 and 0.108, respectively. The ratio correlated positively with the SLEDAI-2K score, proteinuria, and serum anti-dsDNA antibody levels but negatively with C3 and C4 levels. CONCLUSIONS: Our data indicate that the imbalance in Im NK and MD NK cells may play a role in lupus development and serve as a predictive biomarker to assess disease activity and renal involvement in patients with SLE.

Factors associated with 25-hydroxyvitamin D level in Chinese hospitalized patients with systemic lupus erythematosus: a retrospective cohort study.

We aimed to investigate the factors associated with vitamin D deficiency and changes in 25 (OH)D levels, as well as the impact of those changes on disease activity and renal function among SLE patients. This retrospective cohort study was based on the medical records of SLE patients hospitalized between 2010 and 2021. We collected relevant information from this patient population. Logistic regression analysis was employed to determine the factors associated with vitamin D deficiency and increased 25 (OH)D levels, and we calculated the odds ratios (ORs) and 95% confidence intervals (CIs) accordingly. At baseline, among the 1257 SLE patients, the median and interquartile range of 25 (OH)D levels were 14 (9, 20) ng/ml, with 953 (75.8%) patients exhibiting 25 (OH)D deficiency (< 20 ng/ml). The presence of 25 (OH)D deficiency was found to be associated with renal involvement and a high glucocorticoid (GC) maintenance dose. Among the 383 patients who were followed up for an average of 18 months, an increase of at least 100% in 25 (OH)D levels was positively associated with a decreased GC maintenance dose and vitamin D3 supplementation, with adjusted odds ratios(OR) (95% confidence interval [CI]) of 2.16 (1.02, 4.59) and 1300 (70, 22300), respectively. Furthermore, an increased level of 25 (OH)D was significantly associated with a decrease in the Disease Activity Index 2000 score and the urinary protein/creatinine ratio. Patients with SLE have low vitamin D levels, especially those with impaired kidney function. Increased 25 (OH)D levels can be achieved through supplementation with high doses of vitamin D3 and are associated with improvements in disease activity and the urinary protein/creatinine ratio.

Secular trend of mortality and incidence of rheumatoid arthritis in global ,1990-2019: an age period cohort analysis and joinpoint analysis.

BACKGROUND: Rheumatoid arthritis (RA) is a major public health problem. Unfortunately, there is a scarcity of comprehensive and up-to-date information regarding the burden of RA and its dynamic trends in subsequent years. To examine the changing trends in the global burden of RA and forecast for 2044, which will facilitate the development of strategies tailored to RA burden and provide reference for the development of effective treatment guidelines. METHODS: Following the general analytical strategy used the Global Burden of Disease Study (GBD) 2019, which included 204 countries, the age-standardized incidence rate (ASIR), age-standardized mortality rate (ASMR) and age-standardized disability adjusted of life year (DALY) rate for RA were analyzed. RESULTS: The ASIR, ASMR and age-standardized DALY rate for RA in 2019 were 13.001/100,000 (95% UI, 11.833 ~ 14.274), 0.574/100,000 (95% UI, 0.356 ~ 0.793) and 39.565/100,000 (95% UI, 49.529 ~ 30.508), respectively. America had the highest ASIR [18.578(95% UI, 17.147 ~ 20.148)] and age-standardized DALY rate [53.676(95% UI, 40.106 ~ 67.968)] in 2019. Asia had the highest ASMR [0.681(95% UI, 0.802 ~ 0.480)] in 2019. From 1990 to 2019, a significant average annual percentage change (AAPC) in the ASIR was observed in both males [0.237% (95% CI, 0.216 ~ 0.259%)] and females [0.197% (95% CI, 0.141 ~ 0.254%)], AAPC in the ASMR was observed in both males [-0.398% (95% CI, -0.605~-0.191%)] and females [-0.295% (95% CI, -0.424~-0.65%)]. Age effects indicated that the relative risk (RR) of RA-associated incidence and mortality rates increased with age among males and females. The RR of RA increased over time and started to gradually increase from 1990. Cohort effects showed decreases in incidence, mortality and DALY rates in successive birth cohorts. The global incidence of RA would continue to increase in the future, while mortality would continue to decrease. CONCLUSION: The increased risk of RA is dominantly influenced by age effects and period effects and the ethnic area. The results suggest that early identification and treatment of RA is important for reducing the ongoing burden with age, and targeted health education and specific intervention programs should be promoted to control middle-elderly population.

A novel intrarenal multimodal 2D/3D registration algorithm and preliminary phantom study.

Retrograde intrarenal surgery (RIRS) is a widely utilized diagnostic and therapeutic tool for multiple upper urinary tract pathologies. The image-guided navigation system can assist the surgeon to perform precise surgery by providing the relative position between the lesion and the instrument after the intraoperative image is registered with the preoperative model. However, due to the structural complexity and diversity of multi-branched organs such as kidneys, bronchi, etc., the consistency of the intensity distribution of virtual and real images will be challenged, which makes the classical pure intensity registration method prone to bias and random results in a wide search domain. In this paper, we propose a structural feature similarity-based method combined with a semantic style transfer network, which significantly improves the registration accuracy when the initial state deviation is obvious. Furthermore, multi-view constraints are introduced to compensate for the collapse of spatial depth information and improve the robustness of the algorithm. Experimental studies were conducted on two models generated from patient data to evaluate the performance of the method and competing algorithms. The proposed method obtains mean target error (mTRE) of 0.971 ± 0.585 mm and 1.266 ± 0.416 mm respectively, with better accuracy and robustness overall. Experimental results demonstrate that the proposed method has the potential to be applied to RIRS and extended to other organs with similar structures.

Ubiquitylomes and proteomes analyses provide a new interpretation of the molecular mechanisms of rice leaf senescence.

MAIN CONCLUSION: We identified a typical rice premature senescence leaf mutant 86 (psl86) and exhibited the first global ubiquitination data during rice leaf senescence. Premature leaf senescence affects the yield and quality of rice, causing irreparable agricultural economic losses. In this study, we reported a rice premature senescence leaf mutant 86 (psl86) in the population lines of rice (Oryza sativa) japonica cultivar 'Yunyin' (YY) mutagenized using ethyl methane sulfonate (EMS) treatment. Immunoblotting analysis revealed that a higher ubiquitination level in the psl86 mutant compared with YY. Thus, we performed the proteome and ubiquitylome analyses to identify the differential abundance proteins and ubiquitinated proteins (sites) related to leaf senescence. Among 885 quantified lysine ubiquitination (Kub) sites in 492 proteins, 116 sites in 94 proteins were classified as up-regulated targets and seven sites in six proteins were classified as down-regulated targets at a threshold of 1.5. Proteins with up-regulated Kub sites were mainly enriched in the carbon fixation in photosynthetic organisms, glycolysis/gluconeogenesis and the pentose phosphate pathway. Notably, 14 up-regulated Kub sites in 11 proteins were enriched in the carbon fixation in photosynthetic organism pathway, and seven proteins (rbcL, PGK, GAPA, FBA5, ALDP, CFBP1 and GGAT) were down-regulated, indicating this pathway is tightly regulated by ubiquitination during leaf senescence. To our knowledge, we present the first global data on ubiquitination during rice leaf senescence.

Global, regional and national trends in sex- and age-specific disability-adjusted life years of musculoskeletal disorders, 1990-2019.

OBJECTIVE: To quantify the temporal trend of sex- and age-specific disability-adjusted life years (DALYs) for musculoskeletal (MSK) disorders by region and cause. METHODS: Data were collected from the Global Burden of Diseases Study 2019. The estimated annual percentage change (EAPC) by sex, age, region and cause was calculated to examine the temporal trend of the age-standardized DALYs rate (ASDR). The sociodemographic index (SDI) and risk exposures were also examined. RESULTS: Between 1990 and 2019, the global ASDR for MSK disorders remained almost stable by sex and age group but decreased among females ages 0-14 years (EAPC = -0.27). Such age and sex patterns were nearly the same by SDI, except for high SDI regions, where ASDR increased in all subgroups except those ages 15-49 years. The trend in ASDR of MSK disorders for females and males ages 50-74 and ≥75 years increased in ∼80% of countries and territories. The greatest increase was in El Salvador for males ages 15-49 years (EAPC = 1.30), followed by Nicaragua. The association between EAPC and SDI was positive in developing regions, particularly among females ages 15-49 years, and negative in developed regions. A decreasing trend in ASDR was mainly driven by the decrease in low back pain, while the increasing trend was largely due to other MSK disorders and gout across sexes and age groups. CONCLUSIONS: There are great disparities in the age- and sex-specific trends in ASDR by cause on the global, regional and national levels. More differentiated prevention and management strategies are needed for MSK disorders.

Deep learning for gastroscopic images: computer-aided techniques for clinicians.

Gastric disease is a major health problem worldwide. Gastroscopy is the main method and the gold standard used to screen and diagnose many gastric diseases. However, several factors, such as the experience and fatigue of endoscopists, limit its performance. With recent advancements in deep learning, an increasing number of studies have used this technology to provide on-site assistance during real-time gastroscopy. This review summarizes the latest publications on deep learning applications in overcoming disease-related and nondisease-related gastroscopy challenges. The former aims to help endoscopists find lesions and characterize them when they appear in the view shed of the gastroscope. The purpose of the latter is to avoid missing lesions due to poor-quality frames, incomplete inspection coverage of gastroscopy, etc., thus improving the quality of gastroscopy. This study aims to provide technical guidance and a comprehensive perspective for physicians to understand deep learning technology in gastroscopy. Some key issues to be handled before the clinical application of deep learning technology and the future direction of disease-related and nondisease-related applications of deep learning to gastroscopy are discussed herein.

A Novel Central Camera Calibration Method Recording Point-to-Point Distortion for Vision-Based Human Activity Recognition.

The camera is the main sensor of vison-based human activity recognition, and its high-precision calibration of distortion is an important prerequisite of the task. Current studies have shown that multi-parameter model methods achieve higher accuracy than traditional methods in the process of camera calibration. However, these methods need hundreds or even thousands of images to optimize the camera model, which limits their practical use. Here, we propose a novel point-to-point camera distortion calibration method that requires only dozens of images to get a dense distortion rectification map. We have designed an objective function based on deformation between the original images and the projection of reference images, which can eliminate the effect of distortion when optimizing camera parameters. Dense features between the original images and the projection of the reference images are calculated by digital image correlation (DIC). Experiments indicate that our method obtains a comparable result with the multi-parameter model method using a large number of pictures, and contributes a 28.5% improvement to the reprojection error over the polynomial distortion model.

Clinical significance of HScore and MS score comparison in the prognostic evaluation of anti-MDA5-positive patients with dermatomyositis and interstitial lung disease.

OBJECTIVES: To evaluate the clinical significance of the HScore and MS score in the prognosis of anti-melanoma differentiation-associated gene 5 (MDA5) positive patients with dermatomyositis (DM) and interstitial lung disease (ILD). METHODS: The clinical features as well as HScore and MS score were compared between the survivors (n = 61) and nonsurvivors (n = 36) among 97 anti-MDA5-positive DM-ILD patients. Potential prognostic factors were analysed. RESULTS: Compared with survivors, nonsurvivors had significantly older age, tended to be male, and had a significantly higher frequency of fever at disease onset, higher levels of aspartate transaminase, lactate dehydrogenase, and serum ferritin, as well as higher values of HScore and MS score but had a significantly lower frequency of arthritis at disease onset. Multivariate analysis revealed that age ≥50 years [hazard ratio (HR) = 2.70, p = .040, 95% confidence interval (CI) 1.05-6.97)], male gender (HR = 3.20, p = .017, 95% CI 1.23-8.28), and higher HScore (HR = 3.72, p = .003, 95% CI 1.56-8.86) were independent risk factors for mortality. Patients with more risk factors had significantly poorer survival (p < .001). CONCLUSIONS: Older age, high HScore, and male gender are risk factors for poor survival among anti-MDA5-positive DM-ILD patients, suggesting the potential role of macrophage activation in the pathogenesis.

Preliminary demonstration of in vivo quasi-steady-state CEST postprocessing-Correction of saturation time and relaxation delay for robust quantification of tumor MT and APT effects.

PURPOSE: Chemical exchange saturation transfer (CEST) MRI is versatile for measuring the dilute labile protons and microenvironment properties. However, the use of insufficiently long RF saturation duration (Ts) and relaxation delay (Td) may underestimate the CEST measurement. This study proposed a quasi-steady-state (QUASS) CEST analysis for robust CEST quantification. METHODS: The CEST signal evolution was modeled as a function of the longitudinal relaxation rate during Td and spin-lock relaxation rate during Ts, from which the QUASS-CEST effect is derived. Numerical simulation and in vivo rat glioma MRI experiments were conducted at 11.7 T to compare the apparent and QUASS-CEST results obtained under different Ts/Td of 2 seconds/2 seconds and 4 seconds/4 seconds. Magnetization transfer and amide proton transfer effects were resolved using a multipool Lorentzian fitting and evaluated in contralateral normal tissue and tumor regions. RESULTS: The simulation showed the dependence of the apparent CEST effect on Ts and Td, and such reliance was mitigated with the QUASS algorithm. Animal experiment results showed that the apparent magnetization transfer and amide proton transfer effects and their contrast between contralateral normal tissue and tumor regions increased substantially with Ts and Td. In comparison, the QUASS magnetization transfer and amide proton transfer effects and their difference between contralateral normal tissue and tumor exhibited little dependence on Ts and Td. In addition, the apparent magnetization transfer and amide proton transfer were significantly smaller than the corresponding QUASS indices (P < .05). CONCLUSION: The QUASS-CEST algorithm enables robust CEST quantification and offers a straightforward approach to standardize CEST experiments.

Association of antimalarial drugs with decreased overall and cause specific mortality in systemic lupus erythematosus.

OBJECTIVE: To evaluate the association and dose-response pattern between antimalarial drugs and overall and cause specific mortality in SLE patients. METHODS: Medical records including information on HCQ/chloroquine (CQ) prescription were extracted from Jiangsu Lupus database. The database was designed to collect data from SLE patients that first-hospitalized during 1999-2009 in Jiangsu province, China, and a follow-up for survival status was performed in 2010 and 2015. Cox and restricted cubic spline models were used to estimate the hazard ratio and 95% CI. RESULTS: We identified 221 deaths among 2446 SLE patients in total. Compared with non-users, decreased overall mortality was associated with either HCQ or CQ users, with adjusted hazard ratio (95% CI) of 0.49 (0.35, 0.67) and 0.49 (0.27, 0.87), respectively. The association between HCQ/CQ and overall mortality was similar across subgroups, such as patients with comorbidities and organ involvements. Interestingly, both the time and the daily dosage of HCQ/CQ use were related to decreased mortality of SLE in a linear dose-response relationship. In cause specific analyses, HCQ/CQ was inversely associated with death from renal insufficiency and other organ (cardiopulmonary, gastrointestinal and haematological) involvements, with adjusted hazard ratio (95% CI) of 0.23 (0.09, 0.55) and 0.25 (0.10, 0.62), respectively, yet it was not significantly associated with mortality from infection and neuropsychiatric involvements. CONCLUSION: Antimalarial drugs were associated with lower risk of SLE mortality, especially renal insufficiency- and other organ involvement-related death. The protective effects for survival might be augmented by adherence and full dosage of these drugs.

Incidence trend of five common musculoskeletal disorders from 1990 to 2017 at the global, regional and national level: results from the global burden of disease study 2017.

OBJECTIVE: To assess cause-specific incidence and its trend of musculoskeletal (MSK) disorders at global, regional and national levels. METHODS: Data on MSK disorders were downloaded from the Global Burden of Disease 2017 study website. Estimated annual percentage change (EAPC) was calculated to quantify the temporal trend in age-standardised incidence rate (ASR) of MSK disorders, by age, sex, region and cause. RESULTS: Between 1990 and 2017 incident cases of MSK disorders increased globally by 58% from 211.80 million to 334.74 million, with a decreasing ASR of 0.18% annually (95% CI -0.21% to -0.15%). The ASR decreased for low back pain (LBP), remained stable for neck pain (NP), and increased for rheumatoid arthritis (RA), osteoarthritis (OA) and gout, with EAPCs (95% CI) of -0.24 (-0.29 to -0.20), -0.09 (-0.13 to -0.05), 0.36 (0.28 to 0.43), 0.32 (0.28 to 0.36) and 0.22 (0.21 to 0.23), respectively. It appears women have higher increase in EAPC than men for RA (1.3 times) and gout (1.6 times). The absolute EAPC was strikingly high in high or high-middle sociodemographic index (SDI) regions for overall, LBP and gout, and in low SDI regions for NP. EAPC was significantly associated with baseline ASR for LBP (nonlinear), RA (ρ=-0.41) and gout (ρ=-0.42), also with 2017 human development index for LBP (ρ=-0.53) and gout (ρ=0.15). CONCLUSIONS: Globally, MSK disorders remain a public health burden. The ASR is decreasing for MSK disorders overall, mainly in high-middle SDI regions, but increasing for RA, OA and gout.

Family history of liver cancer may modify the association between HBV infection and liver cancer in a Chinese population.

BACKGROUND & AIMS: The potential interaction between family history of liver cancer and HBV infection on liver cancer has not been fully examined. METHODS: We conducted a population-based case-control study composed of 2011 liver cancer cases and 7933 controls in Jiangsu province, China from 2003 to 2010. Data on major risk or protective factors were collected and HBV/HCV sero-markers were assayed using blood samples. Semi-Bayes (SB) adjustments were applied to provide posterior estimates. RESULTS: Both family history of liver cancer (adjusted odds ratios [OR]: 4.32, 95% confidence intervals [CI]: 3.25-5.73) and hepatitis B surface antigen (HBsAg) positivity (adjusted OR: 9.94, 95% CI: 8.33-11.87) were strongly associated with liver cancer development. For individuals with different combinations of serological markers, the adjusted ORs were 8.45 (95% CI: 5.16-13.82) for HBsAg- and HBcAb-positive; 7.57 (95% CI: 4.87-11.77) for HBsAg-, HBeAg- and HBcAb-positive; and 3.62 (95% CI: 2.47-5.31) for HBsAg-, HBeAb- and HBcAb-positive, compared to all negatives in HBV serological markers. One log increase in HBV DNA level was associated with 17% increased risk (adjusted OR: 1.17, 95% CI: 1.03-1.32). The SB-adjusted OR of HBV-positive individuals with family history of liver cancer was 41.34 (95% posterior interval [PI]: 23.69-72.12) compared with those HBV-negative without family history. Relative excess risk due to additive interaction, the attributable proportion and synergy index were 73.13, 0.87 and 8.04 respectively. Adjusted ratio of OR for multiplicative interaction was 2.84 (95% CI: 1.41-5.75). CONCLUSIONS: Super-additive and super-multiplicative interactions may exist between family history of liver cancer and HBV infection on the development of liver cancer.

Interaction between tobacco smoking and hepatitis B virus infection on the risk of liver cancer in a Chinese population.

Although tobacco smoking has been reported as a risk factor for liver cancer, few studies have specifically explored the association among Chinese females and the potential interaction between smoking and other risk factors. A population-based case-control study was conducted and 2,011 liver cancer cases and 7,933 healthy controls were enrolled in Jiangsu, China from 2003 to 2010. Epidemiological data were collected, and serum hepatitis B surface antigen (HBsAg) and anti-HCV antibody were measured. Unconditional logistic regression was used to examine association and potential interaction, while semi-Bayes (SB) method was employed to make estimates more conservative. The prevalence of serum HBsAg positivity was 43.2% among cases and 6.5% among controls. The adjusted odds ratios (OR) for ever smoking were 1.62 (95% confidence interval [CI]: 1.33-1.96) among male and 0.82 (95% CI: 0.53-1.26) among female. Age at first cigarette, duration of smoking and pack-years of smoking were all significantly associated with liver cancer among men. Compared to HBsAg-negative never smokers, the adjusted ORs were 1.25 (95% CI: 1.03-1.52) for HBsAg-negative ever smokers, 7.66 (95% CI: 6.05-9.71) for HBsAg-positive never smokers, and 15.68 (95% CI: 12.06-20.39) for HBsAg-positive ever smokers. These different odds ratios indicated super-additive (RERI: 7.77, 95% CI: 3.81-11.73) and super-multiplicative interactions (ROR: 1.64, 95% CI: 1.17-2.30) between hepatitis B virus (HBV) infection and tobacco smoking. Most associations and interactions detected remained statistically significant after SB adjustments. Tobacco smoking and HBV infection positively interact in the development of liver cancer.

TriFNet: A triple-branch feature fusion network for pH determination by surface-enhanced Raman spectroscopy.

Due to the acidic tumor microenvironment caused by metabolic changes in tumor cells, the accurate pH detection of extracellular fluid is helpful for doctors in precise tumor resection. The combination of Raman spectroscopy and deep learning provides a solution for pH detection. However, most existing studies use one-dimensional convolutional neural networks (1D-CNNs) for spectral analysis, which limits the performance due to insufficient feature extraction. In this work, we propose a 2D triple-branch feature fusion network (TriFNet) for accurate pH determination using surface-enhanced Raman spectra (SERS). Specifically, we design a triple-branch network structure by converting Raman spectra into three types of images to extensively extract complex patterns in spectra. In addition, an attention fusion module, which leverages the complementarity among features in both space and channel, is designed to obtain the valuable information, achieving further accurate pH determination. On our Raman spectral dataset containing 14,137 samples, we achieved mean absolute error (MAE) of 0.059, standard deviation of the absolute error (SD) of 0.07, root mean squared error (RMSE) of 0.092, and coefficient of determination (R2) of 0.991 on the test set. Compared with other published methods, the four metrics showed an average improvement of 47%, 39%, 43%, and 6%, respectively. In addition, visualization validates the diagnostic capability of our model to correlate with biomolecular signatures. Meanwhile, our model has robustness to different SERS chips. These results prove the potential of our method to develop an effective technology based on Raman spectroscopy for accurate pH determination to guide surgery.