HCC EV ECG score: An extracellular vesicle-based protein assay for detection of early-stage hepatocellular carcinoma.

BACKGROUND AND AIMS: The sensitivity of current surveillance methods for detecting early-stage hepatocellular carcinoma (HCC) is suboptimal. Extracellular vesicles (EVs) are promising circulating biomarkers for early cancer detection. In this study, we aim to develop an HCC EV-based surface protein assay for early detection of HCC. APPROACH AND RESULTS: Tissue microarray was used to evaluate four potential HCC-associated protein markers. An HCC EV surface protein assay, composed of covalent chemistry-mediated HCC EV purification and real-time immuno-polymerase chain reaction readouts, was developed and optimized for quantifying subpopulations of EVs. An HCC EV ECG score, calculated from the readouts of three HCC EV subpopulations ( E pCAM + CD63 + , C D147 + CD63 + , and G PC3 + CD63 + HCC EVs), was established for detecting early-stage HCC. A phase 2 biomarker study was conducted to evaluate the performance of ECG score in a training cohort ( n  = 106) and an independent validation cohort ( n  = 72).Overall, 99.7% of tissue microarray stained positive for at least one of the four HCC-associated protein markers (EpCAM, CD147, GPC3, and ASGPR1) that were subsequently validated in HCC EVs. In the training cohort, HCC EV ECG score demonstrated an area under the receiver operating curve (AUROC) of 0.95 (95% confidence interval [CI], 0.90-0.99) for distinguishing early-stage HCC from cirrhosis with a sensitivity of 91% and a specificity of 90%. The AUROCs of the HCC EV ECG score remained excellent in the validation cohort (0.93; 95% CI, 0.87-0.99) and in the subgroups by etiology (viral: 0.95; 95% CI, 0.90-1.00; nonviral: 0.94; 95% CI, 0.88-0.99). CONCLUSION: HCC EV ECG score demonstrated great potential for detecting early-stage HCC. It could augment current surveillance methods and improve patients' outcomes.

Quantitative comparison of the computational complexity of optical, digital and hybrid neural network architectures for image classification tasks.

By implementing neuromorphic paradigms in processing visual information, machine learning became crucial in an ever-increasing number of applications of our everyday lives, ever more performing but also computationally demanding. While a pre-processing of the information passively in the optical domain, before optical-electronic conversion, can reduce the computational requirements for a machine learning task, a comprehensive analysis of computational requirements for hybrid optical-digital neural networks is thus far missing. In this work we critically compare and analyze the performance of different optical, digital and hybrid neural network architectures with respect to their classification accuracy and computational requirements for analog classification tasks of different complexity. We show that certain hybrid architectures exhibit a reduction of computational requirements of a factor >10 while maintaining their performance. This may inspire a new generation of co-designed optical-digital neural network architectures, aimed for applications that require low power consumption like remote sensing devices.

Hysteresis effects of different levels of storm flooding on susceptible enteric infectious diseases in a central city of China.

BACKGROUND: Recently, attention has focused on the impact of global climate change on infectious diseases. Storm flooding is an extreme weather phenomenon that not only impacts the health of the environment but also worsens the spread of pathogens. This poses a significant challenge to public health security. However, there is still a lack of research on how different levels of storm flooding affect susceptible enteric infectious diseases over time. METHODS: Data on enteric infectious diseases, storm flooding events, and meteorology were collected for Changsha, Hunan Province, between 2016 and 2020. The Wilcoxon Rank Sum Test was used to identify the enteric infectious diseases that are susceptible to storm flooding. Then, the lagged effects of different levels of storm flooding on susceptible enteric infectious diseases were analyzed using a distributed lag nonlinear model. RESULTS: There were eleven storm flooding events in Changsha from 2016 to 2020, concentrated in June and July. 37,882 cases of enteric infectious diseases were reported. During non-flooding days, the daily incidence rates of typhoid/paratyphoid and bacillary dysentery were 0.3/100,000 and 0.1/100,000, respectively. During flooding days, the corresponding rates increased to 2.0/100,000 and 0.8/100,000, respectively. The incidence rates of both diseases showed statistically significant differences between non-flooding and flooding days. Correlation analysis shows that the best lags for typhoid/paratyphoid and bacillary dysentery relative to storm flooding events may be 1 and 3 days. The results of the distributed lag nonlinear model showed that typhoid/paratyphoid had the highest cumulative RR values of 2.86 (95% CI: 1.71-4.76) and 8.16 (95% CI: 2.93-22.67) after 4 days of general flooding and heavy flooding, respectively; and bacillary dysentery had the highest cumulative RR values of 1.82 (95% CI: 1.40-2.35) and 3.31 (95% CI: 1.97-5.55) after 5 days of general flooding and heavy flooding, respectively. CONCLUSIONS: Typhoid/paratyphoid and bacillary dysentery are sensitive enteric infectious diseases related to storm flooding in Changsha. There is a lagging effect of storm flooding on the onset of typhoid/paratyphoid and bacillary dysentery, with the best lagging periods being days 1 and 3, respectively. The cumulative risk of typhoid/paratyphoid and bacillary dysentery was highest at 4/5 days lag, respectively. The higher of storm flooding, the higher the risk of disease, which suggests that the authorities should take appropriate preventive and control measures before and after storm flooding.

Cumulative live birth rates after IVF/ICSI cycles with sperm prepared by density gradient centrifugation vs. swim-up: a retrospective study using a propensity score-matching analysis.

BACKGROUND: Density gradient centrifugation (DGC) and swim-up (SU) are the two most widely used sperm preparation methods for in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI). However, existing comparisons of IVF/ICSI outcomes following these sperm preparation methods are insufficient and controversial. METHODS: This retrospective study included all first autologous IVF and ICSI cycles performed between March 1, 2016, and December 31, 2020 in a single university-based center. A total of 3608 cycles were matched between DGC and SU using propensity score (PS) matching for potential confounding factors at a ratio of 1:1. The primary outcome was the cumulative live birth rate (cLBR) per aspiration. RESULTS: PS matching provided 719 cycles after DGC and 719 cycles after SU. After adjusting for confounders, the recovery rate, progressive motility rate after sperm preparation, fertilization rate, good-quality embryo rate, and blastocyst formation rate were similar between the DGC and SU groups. The cLBR (odds ratio [OR] = 1.143, 95% confidence interval [CI]: 0.893-1.461) and LBR per transfer (OR = 1.082, 95% CI: 0.896-1.307) were also not significantly different between the groups. Furthermore, no significant differences were found in all of the laboratory and clinical outcomes following conventional IVF or ICSI cycles between the two groups. However, a significantly higher fertilization rate (ß = 0.074, 95% CI: 0.008-0.140) was observed when using poor-quality sperm in the DGC group than in the SU group. CONCLUSIONS: Sperm preparation using DGC and SU separately resulted in similar IVF/ICSI outcomes. Further studies are warranted to compare the effects of these methods on IVF/ICSI outcomes when using sperm from subgroups of different quality.

Coupling Nanostructured Microchips with Covalent Chemistry Enables Purification of Sarcoma-Derived Extracellular Vesicles for Downstream Functional Studies.

Tumor-derived extracellular vesicles (EVs) play essential roles in intercellular communication during tumor growth and metastatic evolution. Currently, little is known about the possible roles of tumor-derived EVs in sarcoma because the lack of specific surface markers makes it technically challenging to purify sarcoma-derived EVs. In this study, a specific purification system is developed for Ewing sarcoma (ES)-derived EVs by coupling covalent chemistry-mediated EV capture/ release within a nanostructure-embedded microchip. The purification platform-ES-EV Click Chip-takes advantage of specific anti-LINGO-1 recognition and sensitive click chemistry-mediated EV capture, followed by disulfide cleavage-driven EV release. Since the device is capable of specific and efficient purification of intact ES EVs with high purity, ES-EV Click Chip is ideal for conducting downstream functional studies of ES EVs. Absolute quantification of the molecular hallmark of ES (i.e., EWS rearrangements) using reverse transcription Droplet Digital PCR enables specific quantification of ES EVs. The purified ES EVs can be internalized by recipient cells and transfer their mRNA cargoes, exhibiting their biological intactness and potential role as biological shuttles in intercellular communication.

Recent progress in the study of integrated solar cell-energy storage systems.

As fossil fuels continue to deplete, the development of sustainable and green energy sources has become crucial for human societal advancement. Among the various renewable energies, solar energy stands out as a promising substitute for conventional fossil fuels, offering widespread availability and a pollution-free solution. Solar cells, as devices that convert solar energy, are garnering significant focus. However, the intermittent nature of solar energy results in a high dependence on weather conditions of solar cells. Integrated solar cell-energy storage systems that integrate solar cells and energy storage devices may solve this problem by storing the generated electricity and managing the energy output. This review delves into the latest developments in integrated solar cell-energy storage systems, marrying various solar cells with either supercapacitors or batteries. It highlights their construction, material composition, and performance. Additionally, it discusses prevailing challenges and future possibilities, aiming to spark continued advancement and innovation in the sector.

The impact of heat waves on the mortality of Chinese population: A systematic review and meta-analysis.

BACKGROUND: Many studies had shown that with global warming, heat waves may increase the mortality risk of Chinese populations. However, these findings are not consistent. Therefore, we elucidated the associations by meta-analysis and quantified the magnitude of these risks, as well as the underlying factors. METHODS: We searched the China National Knowledge Infrastructure (CNKI), Wanfang database, PubMed, EMBASE, and Web of Science for literature screening up to Nov 10, 2022, to analyze the effect of heat waves on mortality in the Chinese population. Literature screening and data extraction were performed independently by two researchers and the data were merged by meta-analysis. In addition, we conducted subgroup analysis by sex, age, years of education, region, and number of events to explore the source of heterogeneity. RESULTS: Fifteen related studies on the impact on heat waves of the death of Chinese people were included in this study. The results of the meta-analysis showed that heat waves were significantly associated with increased mortality from non-accidental deaths, cardiovascular diseases, stroke, respiratory diseases, and circulatory diseases in the Chinese population: non-accidental mortality (RR = 1.19, 95% CI: 1.13-1.27, P < .01), cardiovascular diseases (RR = 1.25, 95% CI: 1.14-1.38), stroke (RR = 1.11, 95% CI: 1.03-1.20), respiratory diseases (RR = 1.18, 95% CI: 1.09-1.28), and circulatory diseases (RR = 1.11, 95% CI: 1.06-1.17). Subgroup analyses showed that heat waves had a higher risk of non-accidental death for those with <6 years of education than for those with ≥6 years of education. Meta-regression analysis showed that the contribution of the study year to the inter studied heterogeneity was 50.57%. The sensitivity analysis showed that the exclusion of any single study did not materially alter the overall combined effect. The meta-analysis method indicated no obvious evidence of publication bias. CONCLUSIONS: The results of the review indicated that heat waves were associated with increased mortality in the Chinese population, that attention should be paid to high-risk groups, and that public health policies and strategies should be implemented to more effectively respond to and adapt to climate change.

A randomized, double-blind pilot study of analgesic and anti-inflammatory effects of naproxen sodium and acetaminophen following dental implant placement surgery.

Introduction: Post-surgical pain following dental implant placement surgery is typically managed with non-opioid analgesics, including non-steroidal anti-inflammatory drugs (NSAIDs) and acetaminophen. However, the comparative analgesic efficacy of over-the-counter doses of non-steroidal anti-inflammatory drugs and acetaminophen in implant patients is unknown. Therefore, we compared the analgesic and anti-inflammatory effects of naproxen sodium and acetaminophen after surgical placement of one or two dental implants. Methods: Adult patients were treated with naproxen sodium (440 mg loading dose +220 mg q8h, n = 15) or acetaminophen (1,000 mg q6h-max daily dose 3,000 mg, n = 15) for 3 days after implant placement in a randomized, double-blind design. Pain was assessed on a 0-10 scale every 20 min for 6 h after study medication treatment. Tramadol (50 mg) was available as a rescue medication. Plasma and gingival crevicular fluid (GCF) were collected prior to the surgery and 0, 1, 2, 4, 6, 24, and 72 h after surgery for quantification of interleukin (IL)-6, IL-8, and IL-1ß levels. Results: Pain scores were significantly lower in patients treated with naproxen sodium compared to those treated with acetaminophen. Inflammatory mediator levels in plasma and gingival crevicular fluid increased after surgery and returned to near baseline levels by 72 h. Plasma IL-6 levels were significantly lower 6 h after surgery in patients treated with naproxen sodium compared to acetaminophen. No differences in inflammatory mediator concentrations in gingival crevicular fluid were observed between the treatment groups. The number of implants placed and body mass index (BMI) influenced inflammatory mediator concentrations in plasma and gingival crevicular fluid, respectively. Discussion: Naproxen sodium was more effective than acetaminophen in reducing post-operative pain and systemic inflammation following surgical placement of one or two dental implants. Further studies are needed to determine whether these findings are applicable to more complex implant cases and how they affect clinical outcomes following implant placement. Clinical Trial Registration: ClinicalTrials.gov, identifier NCT04694300.

Normal-Range Paternal Serum-Free Thyroxine Concentrations and Outcomes of Assisted Reproductive Technologies.

Background: A recent study showed that paternal subclinical hypothyroidism adversely affects the clinical outcomes of assisted reproductive technologies (ARTs). The aim of this study was to determine whether paternal serum-free thyroxine (fT4) concentrations within the reference range are associated with ART outcomes. Methods: This retrospective cohort study included 4066 couples who received 4894 ART treatment cycles in our clinic between April 1, 2016 and August 31, 2021. The differences in sperm parameters and ART outcomes across the paternal fT4 concentration tertiles were compared by using generalized linear models or generalized estimation equation models. The primary outcomes were clinical pregnancy rate (CPR) and live birth rate (LBR) per oocyte retrieval after the first embryo transfer cycle. Results: The mean ages of the males and their female partners were 32.8 (standard deviation, 5.0) and 30.7 (standard deviation, 4.1) years, respectively. No significant differences were observed in the sperm parameters or ART outcomes between the paternal fT4 concentration tertiles of the overall population. However, a stratified analysis of men aged ≥35 showed an adjusted CPR of 0.36 [confidence interval, CI: 0.27-0.45] for the lower paternal fT4 concentration tertile relative to the middle (adjusted rate: 0.45, CI: 0.38-0.53) and upper (adjusted rate: 0.43, CI: 0.36-0.51) tertiles (p for trend >0.05). The adjusted LBRs were 0.21 [CI: 0.15-0.30] for men aged ≥35 in the lower fT4 concentration tertile (p = 0.024, with reference to the upper tertile), 0.27 [CI: 0.21-0.35] for those in the middle tertile, and 0.30 [CI: 0.23-0.38] for those in the upper tertile. No differences in these outcomes were observed in men aged <35. The nonlinear smoothing curve obtained by using fT4 concentration as a continuous variable further supported these findings. Conclusions: Men of older reproductive age (≥35 years old) with low-normal fT4 concentrations within the reference range are associated with a decreased LBR. Future prospective studies are warranted to confirm the detrimental effects of low-normal paternal fT4 concentrations on ART outcomes.

Assess transmissibility of different influenza subtypes: Based on a SEIABR model.

OBJECTIVE: Influenza is a worldwide public health problem which causes a serious economic and health burden. In order to provide a scientific basis for improving the prevention and control level of influenza, using dynamic model to evaluate the infection rates of influenza different subtypes from 2010 to 2019 in China. METHODS: This article established SEIABR model based on influenza cases reported by China National Influenza Center from 2010 to 2019. And calculated the transmission rate and Re by combined the natural birth rate, natural death rate, infectious rate, proportion of asymptomatic patients, proportion of untreated patients, recovery rate and fatality rate. RESULTS: The average infection rate of influenza was (2.38 ± 0.59) × 10-10, and influenza A was (2.24 ± 0.51) × 10-10, influenza B was (2.21 ± 0.68) × 10-10. And average Re were 1.60, 1.51, 1.49. In addition, the infection rates of A /H1N1, A/H3N2, B/Yamagata and B/Victoria were (2.47 ± 0.51) × 10-10, (2.25 ± 0.48) × 10-10, (2.15 ± 0.61) × 10-10, and (2.30 ± 0.66) × 10-10 and average Re were 1.67, 1.52, 1.44, 1.56. CONCLUSION: Between each year, flu transmission capacity had fluctuation. Influenza A was more transmissible than influenza B, and during the major subtypes, influenza A/H1N1 was the most transmissible.

Repeated social defeat stress inhibits development of hippocampus neurons through mitophagy and autophagy.

The social defeat stress model is commonly used to study depression and anxiety disorder, which can significantly affect the structure and function of neurons in the hippocampus; however, the relevant mechanism in neuronal loss has not been clearly defined. In the present study, a social defeat stress model was established in mice to evaluate the impact of social defeat stress on the structure of neurons in the hippocampus using Western blotting, immunofluorescence, Nissl staining, Golgi staining and transmission electron microscopy. The results demonstrated that social defeat stress leads to disruption of homeostasis in the hippocampus and the integrity of mitochondria in hippocampal neurons was markedly affected by enhanced mitophagy and autophagy resulting in inhibition of development and growth. These findings provide new insights into the mechanisms of neuronal development and growth due to social defeat stress, which should help in the development of new strategies to combat the effects of depression and anxiety disorder.

DNA Methylation Differences Between Zona Pellucida-Bound and Manually Selected Spermatozoa Are Associated With Autism Susceptibility.

Children conceived through intracytoplasmic sperm injection (ICSI) have been reported to have a higher risk of many abnormalities and disorders, including autism and intellectual disability, which may be due to bypassing of the natural sperm selection process during ICSI. Zona pellucida (ZP)-bound spermatozoa (ZPBS) have normal morphology and nuclear DNA. Using these spermatozoa for ICSI results in better outcomes compared with conventional ICSI. However, differences besides morphology that exist between sperm selected by ZP and by an embryologist and whether these differences affect the risk of autism in offspring after ICSI are unclear. To explore these questions, we compared genome-wide DNA methylation profiles between ZPBS and manually selected spermatozoa (MSS)using single-cell bisulfite sequencing. Global DNA methylation levels were significantly lower in ZPBS than in MSS. Using gene ontology (GO) analysis, genes overlapping differentially methylated regions (DMRs) were enriched in biological processes involving neurogenesis. Furthermore, we found that 47.8% of autism candidate genes were associated with DMRs, compared with 37.1% of matched background genes (P<0.001). This was mainly because of the high proportion of autism candidate genes with bivalent chromatin structure. In conclusion, bivalent chromatin structure results in large differences in the methylation of autism genes between MSS and ZPBS. ICSI using MSS, which increases the risk of methylation mutations compared with ZPBS, may lead to a higher risk of autism in offspring.

An Effective Machine Learning Approach for Identifying Non-Severe and Severe Coronavirus Disease 2019 Patients in a Rural Chinese Population: The Wenzhou Retrospective Study.

This paper has proposed an effective intelligent prediction model that can well discriminate and specify the severity of Coronavirus Disease 2019 (COVID-19) infection in clinical diagnosis and provide a criterion for clinicians to weigh scientific and rational medical decision-making. With indicators as the age and gender of the patients and 26 blood routine indexes, a severity prediction framework for COVID-19 is proposed based on machine learning techniques. The framework consists mainly of a random forest and a support vector machine (SVM) model optimized by a slime mould algorithm (SMA). When the random forest was used to identify the key factors, SMA was employed to train an optimal SVM model. Based on the COVID-19 data, comparative experiments were conducted between RF-SMA-SVM and several well-known machine learning algorithms performed. The results indicate that the proposed RF-SMA-SVM not only achieves better classification performance and higher stability on four metrics, but also screens out the main factors that distinguish severe COVID-19 patients from non-severe ones. Therefore, there is a conclusion that the RF-SMA-SVM model can provide an effective auxiliary diagnosis scheme for the clinical diagnosis of COVID-19 infection.

Study of L-Asparaginase, Vincristine, and Dexamethasone Combined With Intensity-modulated Radiation Therapy in Early-Stage Nasal NK/T-Cell Lymphoma.

OBJECTIVES: Natural killer/T-cell lymphoma (NKTCL) is aggressive, and carries a poor prognosis worldwide. This retrospective study aimed to evaluate the clinical efficacy and safety of the LVD regimen (L-asparaginase, vincristine, and dexamethasone) combined with intensity-modulated radiation therapy (IMRT) for the treatment of early-stage nasal NKTCL in a Chinese population. METHODS: The clinical data were collected from patients treated between March 2010 and January 2017. Patients received LVD chemotherapy combined with IMRT, and were followed for 30 to 90 months. All received radiotherapy at the end of the first/second cycle of chemotherapy. The survival curves were generated by the Kaplan-Meier method. RESULTS: Among 94 patients who received 2 to 6 cycles (mean, 4 cycles) of treatments, 56 and 25 achieved complete and partial remission, respectively; 2 and 11 experienced stable disease and progressive disease. The overall objective response was 86.2%. Patients with elevated lactate dehydrogenase and skin invasion had a lower objective response rate. The progression-free survival rates at 1, 3, and 5 years were 90.3%, 73.5%, and 71.3%; the corresponding overall survival rates were 91.4%, 74.3%, and 74.3%. The main adverse events were myelosuppression (63.8% grades I to II, 12.8% grade III), gastrointestinal symptoms (63.8% grades I to II), hepatic lesion (55.3% grades I to II), hypoproteinemia (46.8% grades I to II), skin allergies (77.7% grades I to II, 3.2% grade III), and oral mucosal lesions (44.7% grades I to II, 33% grade III). No severe pancreatitis, anaphylaxis, or toxicity-related death was observed. CONCLUSION: In patients with early-stage nasal NKTCL, our LVD-IMRT regimen produced excellent, durable therapeutic benefit in most patients, with acceptable toxicity and no acute mortality.

Dual Supramolecular Nanoparticle Vectors Enable CRISPR/Cas9-Mediated Knockin of Retinoschisin 1 Gene-A Potential Nonviral Therapeutic Solution for X-Linked Juvenile Retinoschisis.

The homology-independent targeted integration (HITI) strategy enables effective CRISPR/Cas9-mediated knockin of therapeutic genes in nondividing cells in vivo, promising general therapeutic solutions for treating genetic diseases like X-linked juvenile retinoschisis. Herein, supramolecular nanoparticle (SMNP) vectors are used for codelivery of two DNA plasmids-CRISPR-Cas9 genome-editing system and a therapeutic gene, Retinoschisin 1 (RS1)-enabling clustered regularly interspaced short palindromic repeats (CRISPR)-associated protein 9 (CRISPR/Cas9) knockin of the RS1 gene with HITI. Through small-scale combinatorial screenings, two SMNP vectors, with Cas9 and single guide RNA (sgRNA)-plasmid in one and Donor-RS1 and green fluorescent protein (GFP)-plasmid in the other, with optimal delivery performances are identified. These SMNP vectors are then employed for CRISPR/Cas9 knockin of RS1/GFP genes into the mouse Rosa26 safe-harbor site in vitro and in vivo. The in vivo study involves intravitreally injecting the two SMNP vectors into the mouse eyes, followed by repeated ocular imaging by fundus camera and optical coherence tomography, and pathological and molecular analyses of the harvested retina tissues. Mice ocular organs retain their anatomical integrity, a single-copy 3.0-kb RS1/GFP gene is precisely integrated into the Rosa26 site in the retinas, and the integrated RS1/GFP gene is expressed in the retinas, demonstrating CRISPR/Cas9 knockin of RS1/GFP gene.