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Abstract This article provides an example of the ways in which remote sensing, Earth observation, and machine learning can be deployed to provide the most up to date quantitative portrait of the South Asian ‘Brick Belt’, with a view to understanding the extent of the prevalence of modern slavery and exploitative labour. This analysis represents the first of its kind in estimating the spatiotemporal patterns in the Bull’s Trench Kilns across the Brick Belt, as well as its connections with various UN Sustainable Development Goals (SDGs). With a principal focus on Sustainable Development Goal Target 8.7 regarding the effective measures to end modern slavery by 2030, the article provides additional evidence on the intersections that exist between SDG 8.7 and those relating to urbanisation (SDG 11, 12), environmental degradation and pollution (SDG 3, 14, 15), and climate change (SDG 13). Our findings are then used to make a series of pragmatic suggestions for mitigating the most extreme SDG risks associated with brick production in ways that can improve human lives and human freedom.

The relationship of single nucleotide polymorphisms (SNPs) in COL4A2 gene with risk and outcome of primary intracerebral hemorrhage (ICH) in the Chinese Han population remains unclear, which was investigated in this study. Primary ICH patients and non-stroke controls of Chinese Han ethnicity were enrolled. The genotypes of 8 tag-SNPs were determined using a custom-by-design 48-Plex SNPscan Kit. Poor 3-month outcome was defined as modified Rankin Scale score 4–6. Logistic regression was employed to examine association between COL4A2 variants and risk and poor outcome of primary ICH. 323 patients with primary ICH and 376 stroke-free controls were included. Compared to controls, the rs1049931 G and rs1049906 C alleles were associated with increased ICH risk (p = 0.027 and 0.033), and these two allele counts increased this risk after adjustments respectively (additive model: adjusted OR [aOR] 1.41, 95% CI 1.03–1.94, corrected p = 0.043; aOR 1.37, 95% CI 1.01–1.86, corrected p = 0.043). The rs1049931 AG/GG and rs1049906 CT/CC genotypes showed increased susceptibility to non-lobar hemorrhage (aOR 1.63, 95% CI 1.06–2.50, p = 0.025; aOR 1.63, 95% CI 1.07–2.47, p = 0.022). Haplotype analysis revealed an association between rs1049906-rs1049931 haplotype CG and ICH risk (OR 1.36, 95% CI 1.05–1.78, p = 0.021). Regarding clinical outcome, the rs3803230 C allele (dominant model: aOR 1.94, 95% CI 1.04–3.63, p = 0.037) and haplotype AC of rs7990214-rs3803230 (OR 1.98, 95% CI 1.13–3.46, p = 0.015) contributed to 3-month poor outcome. The COL4A2 polymorphisms are associated with an increased risk of primary ICH, mainly non-lobar hemorrhage, and with long-term poor outcome after ICH in Chinese Han population. [ABSTRACT FROM AUTHOR]

Proteinuria is a biomarker of kidney injury that typically results from glomerular and/or tubulointerstitial disease. Whereas kidney impairment with normal urinary protein excretion is usually less focused and understudied. We conducted a retrospective review of the renal histopathology of the patients with variable degrees of unexplained renal insufficiency but with normal range proteinuria between 2014 and 2024 of three university teaching hospitals in Shenzhen city of Southern China. Patients with kidney dysfunction of undetermined or uncertain etiology and with normal urinary protein excretion (defined by a 24hr urinary protein excretion < 150 mg or spot urinary protein to creatinine ratio [PCR] < 150 mg/g) were enrolled and analyzed. In a total of 2405 patients, 53 (2.2%) fulfilled the inclusion criteria (male/female 40/13, age 47.3 ± 14.3 years) with a mean eGFR of 46.6 ± 16.8 ml/min per 1.73 m2. Glomerular disease (GD) was the most frequent pathological finding identified in 23 (43.4%) patients, while 19 (35.8%) cases showed tubulointerstitial disease (TID) and 11 (20.8%) patients exhibited small vascular disease (SVD). Patients in the TID had the lowest mean eGFR and the highest numerical 24hr urinary protein excretion among the three groups. The incidence of acute kidney injury was significantly higher in TID than in other two groups. The patients in the SVD group had the highest fraction of underlying hypertension. Kidney dysfunction with normal range proteinuria may be related with, in descending order of probablity, glomerular, tubulointerstitial and small vascular diseases. Renal biopsies were proved useful in informing therapeutic choice, long-term management and in predicting prognosis in this setting. [ABSTRACT FROM AUTHOR]

The locked segment is critical for determining the stability of locked segment-type landslides. Research indicates that the volume expansion point marks the transition from the secondary creep stage to the tertiary creep stage in a landslide's evolution, and also separates the stable crack growth stage from the unstable crack growth stage in the locked segment. Identifying the volume expansion point is essential for early warning and predicting locked segment-type landslides. A series of instruments (resistance strain gauges, acoustic emission system, piezoelectric acceleration sensors, etc.) were used to conduct physical model tests of the landslide with retaining-wall-like locked segment under external load on the landslide's trailing edge. The evolution process of this landslide was analyzed through changes in slope shape and stress response characteristics. The experimental results reveal the failure mechanism of the landslide with retaining-wall-like locked segment: the upper part of the landslide thrusts and slides, the middle part squeezes and uplifts, the retaining-wall-like locked segment produces a locking effect, and compression-shear fracture of the retaining-wall-like locked segment leads to landslide failure. Based on the deformation and acoustic emission characteristics of the locked segment, a method for identifying the volume expansion point was established. This point was used as the onset of acceleration point in the inverse velocity method to predict the failure time of the locked segment-type landslides, incorporating the three-stage creep model and Fukumoto's theory. [ABSTRACT FROM AUTHOR]

Reservoir dispatching regulations are a crucial basis for reservoir operation, and using information extraction technology to extract entities and relationships from heterogeneous texts to form triples can provide structured knowledge support for professionals in making dispatch decisions and intelligent recommendations. Current information extraction technologies require manual data labeling, consuming a significant amount of time. As the number of dispatch rules increases, this method cannot meet the need for timely generation of dispatch plans during emergency flood control periods. Furthermore, utilizing natural language prompts to guide large language models in completing reservoir dispatch extraction tasks also presents challenges of cognitive load and instability in model output. Therefore, this paper proposes an entity and relationship extraction method for reservoir dispatch based on structured prompt language. Initially, a variety of labels are refined according to the extraction tasks, then organized and defined using the Backus–Naur Form (BNF) to create a structured format, thus better guiding large language models in the extraction work. Moreover, an AI agent based on this method has been developed to facilitate operation by dispatch professionals, allowing for the quick acquisition of structured data. Experimental verification has shown that, in the task of extracting entities and relationships for reservoir dispatch, this AI agent not only effectively reduces cognitive burden and the impact of instability in model output but also demonstrates high extraction performance (with F1 scores for extracting entities and relationships both above 80%), offering a new solution approach for knowledge extraction tasks in other water resource fields. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to investigate the correlation between chromosomal abnormalities in spontaneous abortion with clinical features and seek copy number variations (CNVs) and genes that might be connected to spontaneous abortion. Methods: Over 7 years, we used CNV-seq and STR analysis to study POCs, comparing chromosomal abnormalities with clinical features and identifying critical CNVs and genes associated with spontaneous abortion. Results: Total chromosomal variants in the POCs were identified in 66.8% (2169/3247) of all cases, which included 45.2% (1467/3247) numerical abnormalities and 21.6% (702/3247) copy number variants (CNVs). Chromosome number abnormalities, especially aneuploidy abnormalities, were more pronounced in the group of mothers aged ≥ 35 years, the early miscarriage group, and the chorionic villi group. We further analyzed 212 pathogenic and likely pathogenic CNVs in 146 POCs as well as identified 8 statistically significant SORs through comparison with both a healthy population and a group of non-spontaneously aborted fetuses. Our analysis suggests that these CNVs may play a crucial role in spontaneous abortion. Furthermore, by utilizing the RVIS score and MGI database, we identified 86 genes associated with spontaneous abortion, with particular emphasis on PARP6, ISLR, ULK3, FGFRL1, TBC1D14, SCRIB, and PLEC. Conclusion: We found variability in chromosomal abnormalities across clinical features, identifying eight crucial copy number variations (CNVs) and multiple key genes that may be linked to spontaneous abortion. This research enhances the comprehension of genetic factors contributing to spontaneous abortion. [ABSTRACT FROM AUTHOR]

The evolution processes of complex systems carry key information in the systems' functional properties. Applying machine learning algorithms, we demonstrate that the historical formation process of various networked complex systems can be extracted, including protein-protein interaction, ecology, and social network systems. The recovered evolution process has demonstrations of immense scientific values, such as interpreting the evolution of protein-protein interaction network, facilitating structure prediction, and particularly revealing the key co-evolution features of network structures such as preferential attachment, community structure, local clustering, degree-degree correlation that could not be explained collectively by previous theories. Intriguingly, we discover that for large networks, if the performance of the machine learning model is slightly better than a random guess on the pairwise order of links, reliable restoration of the overall network formation process can be achieved. This suggests that evolution history restoration is generally highly feasible on empirical networks. Evolution processes of complex networked systems in biology and social sciences, and their underlying mechanisms, still need better understanding. The authors propose a machine learning approach to reconstruct the evolution history of complex networks. [ABSTRACT FROM AUTHOR]

In this study, the influence of a vertical load on the deformation of a suspended plastic cutoff wall and the evolution of the piping of a dike foundation were studied through model tests and numerical analysis methods. The results of the numerical analysis were in good agreement with those of the model tests. Under vertical load and seepage force, the suspended plastic cutoff wall has well co-deformation with soil, and the mud permeable zone plays the role of "bridge"; the vertical load can increase the critical hydraulic gradient and failure hydraulic gradient and the corresponding upstream waterhead of dike foundation, and the influence of failure hydraulic gradient is greater than that of critical hydraulic gradient. In addition, the numerical analysis method obtains the distribution and variation in the hydraulic gradient along the piping channel from the pre-set orifice to the inlet, which provides reliable data support for the analysis of the evolution mechanism of dike foundation piping. The study also proves that the mud penetration belt plays a synergistic and auxiliary role in the prevention of dike foundation piping by the suspended cutoff wall, which provides strong support for further understanding of the mechanism of preventing dike foundation piping by the cutoff wall. [ABSTRACT FROM AUTHOR]

Objective: Spinal muscular atrophy (SMA) is an autosomal recessive disorder mainly affecting the neuromuscular system, which seriously threatens the life and health of patients. But few studies have reported the acceptance rate of SMA gene screening and SMA carrier rate in China. The present study aimed to clarify the two issues in China through a retrospective analysis of 18,818 reproductive age women in Wuhan area of China. Methods: The copy number (CN) of exons 7 and 8 in survival motor neuron 1 (SMN1) gene was detected by real-time quantitative PCR, and the results were verified by multiplex ligation-dependent probe amplification. Results: Carrier screening was offered to 44,953 women of childbearing age in our medical center from March, 2018, to February, 2022, of whom 18,818 were enrolled in the program. A total of 336 women were identified as carriers (1.73%; 326/18,808; without fertility history of the children with SMA). Among 18,818 reproductive age women, 286 spouses (85.12%; 286/336) were successfully recalled for screening. The results showed 17 couples at high risk of having children with SMA, of whom prenatal diagnosis was implemented in 11, and 6 fetuses were identified with SMA. All the 5 pregnant women bearing the 6 SMA fetuses chose to terminate the pregnancy by artificial abortion. Conclusion: Reproductive age women and their spouses in Wuhan area showed a positive attitude toward general screening for SMA carriers. Given the high early mortality of children with SMA, screening for SMA carriers in women of reproductive age is necessary and feasible. [ABSTRACT FROM AUTHOR]

Objective: To assess the efficacy of copy number variation sequencing (CNV-seq) and karyotyping for prenatal detection of chromosomal abnormalities in fetuses with increased nuchal translucency. Methods: Amniotic fluid samples were extracted from 205 fetuses with increased nuchal translucency (NT ≥ 2.5 mm), diagnosed by ultrasound between gestational ages of 11 and 13 + 6 weeks. Karyotyping and CNV-seq were performed for detecting chromosomal abnormalities. Results: There are 40 fetuses (19.51%) showing increased NT detected with chromosomal abnormalities in karyotyping, and trisomy 21 was found to be the most common abnormalities. There are 50 fetuses (24.39%) identified with chromosomal abnormalities by CNV-seq. The detection of the applied techniques indicated that CNV-seq revealed higher chromosomal aberrations. The risk of chromosomal abnormalities was significantly increased with NT thickening, from 13.64% in the NT group of 2.5–3.4 mm, 38.64% in the NT group of 3.5–4.4 mm, and to 51.72% in the NT group of over 4.5 mm (P < 0.05). The investigated cases with increased NT with presence of soft markers in ultrasound or high risk in non-invasive prenatal testing presented chromosomal abnormalities in higher rates, comparing with those with isolated NT or low risk (P < 0.05). Conclusion: The results indicated that the risk of chromosomal abnormalities was associated with the NT thickness, detected by karyotype or CNV-seq. The combination application of two analysis was efficient to reveal the possible genetic defects in prenatal diagnosis. The finding suggested that the detection should be considered with ultrasonographic soft markers, and the NT thickness of 2.5–3.4 mm could be a critical value for detecting chromosomal abnormalities to prevent the occurrence of missed diagnosis. [ABSTRACT FROM AUTHOR]

Objectives: To explore the feasibility of making a submental perforator flap distal to the connecting line between the mastoid and the sternoclavicular joint under the guidance of neck-enhanced CT and repairing the postoperative defect of upper airway malignancy. Materials and methods: This study retrospectively analysed 19 cases of upper airway malignant tumours treated in our department from January 2021 to September 2022, including 17 males and 2 females, aged 43–70 years. Site of lesions: 15 cases were in the laryngopharynx, 2 cases in the nasal cavity and paranasal sinus and 2 cases on the soft palate. All the lesions were malignant and at stages T2–4N0–2M0. Surgical method: The extended submental perforator flap (size 22–15 × 6–7 cm) was prefabricated distal to the connecting line between the mastoid and the sternoclavicular joint. After tumour resection, the flap was used to repair the postoperative defect. Fifteen cases of laryngopharyngeal malignant tumours were repaired using the extended submental perforator flap with the vascular pedicle located on the opposite side of the tumour body. Two cases of nasal cavity and paranasal sinus tumours were repaired using the extended submental perforator flap combined with the temporalis muscle flap. The soft palate was completely removed in two patients with soft palate cancer and repaired using the folded extended submental perforator flap. Results: Before the surgery, the reflux vein was observed by neck-enhanced CT, including 12 cases returning to the internal jugular vein and 7 cases to the external jugular vein. All 19 cases in which flaps were used survived, and 1 case had a postoperative infection. All the patients had nasal feeding removed after surgery. The tracheal cannula was removed from the patients with laryngeal preservation, and the pronunciation was satisfactory. Among them, patients with soft palate cancer repair had mild nasal reflux symptoms with smooth breathing. During the follow-up period of 4–24 months, 18 patients had no tumour recurrence or metastasis, and 1 patient had cervical lymph node metastasis. Conclusions: This study highlights the use of a submental perforator flap distal to the connecting line between the mastoid and the sternoclavicular joint to repair postoperative defects for upper airway malignancy as an innovative surgical approach that provides more tissue and good arteriovenous blood supply to adjacent sites. This method has high clinical value and provides an effective option for repairing postoperative defects of upper airway malignancy. [ABSTRACT FROM AUTHOR]

Mining-triggered tremor is an important factor that restricts the safe production of coal mines. Studying the occurrence mechanism of these tremors is integral to preventing and controlling rockbursts. This study jointly uses Bayesian full-waveform inversion and simulation to determine the relationship between roadway layout, syncline, and rockburst accidents in the Xinjulong coal mine. Field investigations verified that the static stress transfer caused by event #14 triggered the occurrence of a rockburst. Moreover, the stress and displacement field changes caused by sources with different friction coefficients and depths were discussed. The results show that (1) a shear rupture was observed after event #14, and the fault type was strike–slip. (2) Meanwhile, a stress-increase zone appeared at both ends of the fault plane, and the roadway in this zone was prone to rockburst risks. In addition, there are stress-increasing and decreasing zones on both sides of the fault plane. (3) With the increasing friction coefficient ( μ i ), the stress and displacement near the fault plane increase slightly. When the source was less than 60 m away from the roadway, its stability was mainly affected by event #14. When the distance is more than 60 m, it is mainly affected by the Liuhai syncline, which can reveal the mechanism of rockbursts triggered by strike–slip tremors and provide a reference for preventing rockburst disasters. Highlights: The rationality of the Bayesian full-waveform inversion results was verified based on the roadway damage situation. The stress state of fault plane after mining-triggered tremor and its influence on roadway are analyzed. The relationships among Coulomb stress, Syncline, distance and friction coefficient during the rupture of event #14 were analyzed. [ABSTRACT FROM AUTHOR]

As China's economy enters the stage of high-quality development, the sustainability of development becomes increasingly important. Therefore, this study takes air quality index as the explanatory variable, the level of shadow banking as the explained variable, and environmental regulation as the intermediary variable to empirically study whether environmental regulation caused by air pollution will affect the shadow banking of non-financial enterprises. The findings suggest that air pollution is likely to strengthen environmental regulation, thereby reducing the level of shadow banking, as air pollution strengthens environmental regulation, leading to the reduction of implicit government guarantees, while enterprises tend to abandon or minimize reliance on these guarantees and reduce leverage. The mechanism test shows that the ESG performance of non-financial firms weakens the process by which air pollution reduces the degree of shadow banking of non-financial firms, while the short-sightedness of management enhances this process. Heterogeneity analysis shows that this process is more significant under the effect of market-driven environmental regulation and in private enterprises and enterprises in regions with large industrial scale. Therefore, the policy implication is that government should continue to strengthen environmental law enforcement in future supervision, as this can not only reduce pollution levels but also reduce systemic financial risks. Enterprises should also increase their sense of social responsibility. [ABSTRACT FROM AUTHOR]

Pentafluorosulfanylated (SF5-) aromatics have shown great potential in drugs, and the bioisosteric replacement of aromatic ring with bicyclo[1.1.1]pentane (BCP) unit has attracted considerable attention recently. Consequently, pentafluorosulfanylated bicyclo[1.1.1]pentanes (SF5-BCPs) should have application in the realm of drug discovery. In this study, a one-pot iodopentafluorosulfanylation of [1.1.1]propellane with SF5Cl and CH2I2 for the practical synthesis of iodopentafluorosulfanylated bicyclo[1.1.1]pentane (SF5-BCP-I) was developed. SF5-BCP-I was the first example of SF5-BCPs that could be transformed. The first general method to access SF5-substituted bicyclo[1.1.1]pentane derivatives was demonstrated through photoredox-catalyzed radical addition of SF5-BCP-I to alkenes and alkynes. [ABSTRACT FROM AUTHOR]

The COVID-19 infection cases have surged globally, causing devastations to both the society and economy. A key factor contributing to the sustained spreading is the presence of a large number of asymptomatic or hidden spreaders, who mix among the susceptible population without being detected or quarantined. Due to the continuous emergence of new virus variants, even if vaccines have been widely used, the detection of asymptomatic infected persons is still important in the epidemic control. Based on the unique characteristics of COVID-19 spreading dynamics, here we propose a theoretical framework capturing the transition probabilities among different infectious states in a network, and extend it to an efficient algorithm to identify asymptotic individuals. We find that using pure physical spreading equations, the hidden spreaders of COVID-19 can be identified with remarkable accuracy, even with incomplete information of the contract-tracing networks. Furthermore, our framework can be useful for other epidemic diseases that also feature asymptomatic spreading. [ABSTRACT FROM AUTHOR]

Itch is an annoying sensation consisting of both sensory and emotional components. It is known to involve the parabrachial nucleus (PBN), but the following transmission nodes remain elusive. The present study identified that the PBN-central medial thalamic nucleus (CM)-medial prefrontal cortex (mPFC) pathway is essential for itch signal transmission at the supraspinal level in male mice. Chemogenetic inhibition of the CM-mPFC pathway attenuates scratching behavior or chronic itch-related affective responses. CM input to mPFC pyramidal neurons is enhanced in acute and chronic itch models. Specifically chronic itch stimuli also alter mPFC interneuron involvement, resulting in enhanced feedforward inhibition and a distorted excitatory/inhibitory balance in mPFC pyramidal neurons. The present work underscores CM as a transmit node of the itch signal in the thalamus, which is dynamically engaged in both the sensory and affective dimensions of itch with different stimulus salience. Itch is known to involve the parabrachial nucleus, but the following transmission nodes remain elusive. Here, the authors show in male mice that the central medial thalamic nucleus—medial prefrontal cortex (mPFC) pathway transmits itch signals and is involved in both acute scratching and chronic itch-related affective behavior, with an altered excitatory/inhibitory balance in mPFC in chronic itch models. [ABSTRACT FROM AUTHOR]

It is known that each compact connected orientable 3-manifold M with boundary admits an H′-splitting H1 ∪FH2, where F is a compact connected orientable surface properly embedded in M and splits M into two handlbodies H1 and H2. In this paper, we show that a non-completely L-reducible and minimal H′-splitting surface for a compact connected irreducible orientable anannular Seifert 3-manifold with boundary is horizontal, and give a necessary and sufficient condition for an amalgamation of two compact connected orientable 3-manifolds along a compact connected surface to be a Seifert manifold with boundary, and describe a characteristic of some H′-splittings to denote a Seifert 3-manifold with boundary. For a compact connected orientable Seifert manifold M with a semi-bundle structure M1 ∪FM2, we give an upper bound of the genus of the base surface. [ABSTRACT FROM AUTHOR]

Forensic DNA analysis of semen-vaginal fluid mixed stains is essential and necessary in sexual assault cases. Here, we used a magnetic bead conjugated acrosin binding protein (ACRBP) antibody to separate and enrich sperm cells from mixed stains. Previously, western blotting indicated that ACRBP was specifically expressed in sperm cells, but not in female blood and epithelial cells, while immunofluorescence data showed ACRBP was localized to the acrosome in sperm cells. In our study, sperm were separated from mixed samples at three sperm cell/female buccal epithelial cell ratios (103:103; 103:104; and 103:105) using a magnetic bead conjugated ACRBP antibody. Subsequently, 23 autosomal short tandem repeat (STR) loci were amplified using the Huaxia™ Platinum PCR Amplification System and genotyped using capillary electrophoresis. The genotyping success rate for STR loci was 90% when the sperm to female buccal epithelial cell ratio was > 1:100 in mixed samples. Our results suggest that the magnetic bead conjugated ACRBP antibody is effective for isolating sperm cells in sexual assault cases. [ABSTRACT FROM AUTHOR]

The ubiquitin-specific protease 14 (USP14) is a deubiquitinating enzyme, its inhibitor was reported could alleviate the ischemia/reperfusion (I/R)-stimulated cerebral neuronal damage. However, its specific role in I/R-induced acute kidney injury (AKI) remains unclear. We established hypoxia/reoxygenation (H/R)-induced HK-2 cell injury model in vitro and I/R-induced kidney injury mice model in vivo. The expression or activity of USP14 was inhibited by siRNA or IU1, a small molecule inhibitor of USP14. ROS were scavenged by N-acetyl-cysteine (NAC). Biochemical index analysis and hematoxylin & eosin (H&E) staining were performed to evaluate renal injury. The results indicated that USP14 was upregulated in H/R-induced HK-2 cells and kidney tissues of I/R mice. Inhibition of USP14 suppressed the cell death, inflammatory, oxidative stress and reactive oxygen species (ROS)-dependent ferroptosis of H/R-induced HK-2 cells. What's more, IU1 and NAC effectively alleviated renal injury of I/R mice. In summary, this study suggested that inhibition of USP14 protected renal from I/R injury. [ABSTRACT FROM AUTHOR]

We study the use of the self-Kerr and cross-Kerr nonlinearities to realize strong photon blockade in a weakly driven, four-mode optomechanical system. According to the Born—Oppenheimer approximation, we obtain the cavity self-Kerr coupling and the inter-cavity cross-Kerr coupling, adiabatically separated from the mechanical oscillator. Through minimizing the second-order correlation function, we find out the optimal parameter conditions for the unconventional photon blockade. Under the optimal conditions, the strong photon blockade can appear in the strong or weak nonlinearities. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Zhejiang University: Science B is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

We investigate the use of the cross-Kerr nonlinearity to realize strong photon blockade in a weakly driven, three-mode system. The results show that the conventional photon blockade induced by the strong nonlinearities and the unconventional photon blockade induced by quantum interference effects exist in our system. In particular, we find that the CPB only appears in the strong cross-Kerr coupling regime, while the UPB can occur in the weak or strong cross-Kerr coupling regime. For the strong cross-Kerr nonlinearities, both CPB and UPB exhibit strong antibunching features. Furthermore, the switch between CPB and UPB can be achieved with different detunings. Our work paves the way to study two different physical mechanisms behind CPB and UPB. [ABSTRACT FROM AUTHOR]

Background: Early neurological deterioration (END) after endovascular thrombectomy (EVT) is strongly associated with poor prognosis in patients with large vessel occlusion. The relationship between body temperature and END after EVT is unknown, which we aimed to investigate in this study. Methods: END was defined as an increase of four or more points on the National Institutes of Health Stroke Scale score compared with the baseline assessment within 24 h. Logistic regression and restricted cubic spline models were used to assess the relationship between body temperature and END. Results: Among 7741 consecutive patients with ischemic stroke, 406 patients with large vessel occlusion who underwent EVT were enrolled. In total, 88 (21.7%) patients developed END. Logistic regression showed that the maximum body temperature within 24 h (odds ratio [OR] = 1.97 per °C, 95% confidence interval [CI] 1.17–3.32, p = 0.010) was independently associated with END. This association was nonlinear and J shaped (p for nonlinearity = 0.010), and the risk of END increased when the maximum body temperature within 24 h was lower or higher than 37.0 °C. Fever burden is also independently associated with END (OR = 1.06 per °C × hour, 95% CI 1.01–1.11, p = 0.012). In addition, the timing of fever onset was independently associated with END, and the highest risk of END was associated with fever onset within 6 h after EVT (OR = 3.92, 95% CI 1.25–12.27, p = 0.019). Conclusions: In summary, there is a J-shaped association between the maximum body temperature within 24 h after EVT and END. Moreover, the risk of END differed according to the timing of fever onset. [ABSTRACT FROM AUTHOR]

The most dominant arbuscular mycorrhizal (AM) symbiont can be established on roots of most terrestrial plants by beneficial AM fungi. A type of polycationic and aliphatic compounds, polyamines (PAs), are involved in plant physiological activities including stress responses. Interestingly, small amounts of PAs such as putrescine (Put) and spermidine (Spd) were found in AM fungal spores, and they are considered to be a component involved in mycorrhizal development, including mycorrhizal colonization, appressoria formation, spore germination and mycelial growth. Thus, PAs are regulatory factors in plant-AM symbiosis. Inoculation of AM fungi also affects the metabolism of endogenous PAs in host plants, including PAs synthesis and catabolism, thus, regulating various physiological events of the host. As a result, there seems to be a dialogue between PAs and AM fungi. Existing knowledge makes us understand that endogenous or exogenous PAs are an important regulator factor in the growth of AM fungi, as well as a key substance to colonize roots, which further enhances mycorrhizal benefits in plant growth responses and root architecture. The presence of AM symbiosis in roots alters the dynamic balance of endogenous PAs, triggering osmotic adjustment and antioxidant defense systems, maintaining charge balance and acting as a stress signalling molecule, which affects various physiological activities, such as plant growth, nutrient acquisition, stress tolerance and improvement of root architecture. This review mainly elucidated (i) what is the role of fungal endogenous PAs in fungal growth and colonization of roots in host plants? (ii) how AM fungi and PAs interact with each other to alter the growth of fungi and plants and subsequent activities, providing the reference for the future combined use of AM fungi and PAs in agricultural production, although there are still many unknown events in the dialogue. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Central South University is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Purpose: To investigate the potential mechanisms of miR-211-3p on induction chemotherapy (IC) sensitivity in hypopharyngeal squamous cell carcinoma (HSCC). Methods: qRT-PCR was assessed to compare the miR-211-3p expression between IC sensitive and insensitive tumor tissues. The MTT assay was performed to analyze cell proliferation and viability to paclitaxel after alteration of miR-211-3p. Flow cytometry assay was conducted to explore cell apoptosis. Transwell assay was used to explore the effect of miR-211-3p on cell migration. Transcriptome sequencing was then performed to select differentially expressed genes (DEGs) after over-expression of miR-211-3p. GO and KEGG enrichment analyses were conducted to annotate DEGs. PPI analysis was conducted to screen candidate genes. The differential expression and survival status of candidate genes were further validated in TCGA-HNSCC data. The single sample GSEA method was used to investigate the association between downstream genes and immune cell infiltration. Results: miR-211-3p was up-regulated in IC insensitive larynx–hypopharyngeal tumor tissues. Over-expression of miR-211-3p promoted cell proliferation and migration, and inhibited apoptosis. The IC50 value of miR-211-3p overexpression (OE) group was significantly higher than negative control (NC) group treated with paclitaxel, suggesting miR-211-3p enhanced IC insensitivity in HSCC. We found 778 DEG after over-expression of miR-211-3p and 11 significant genes were then identified. Finally, colony stimulating factor 2 (CSF2) and C-C motif chemokine ligand 20 (CCL20) were validated to be significantly high expressed and associated with poorer overall survival in head and neck squamous cell carcinoma, which were involved in TNF signaling pathway and then regulated immune cell infiltration. Conclusion: The miR-211-3p could promote HSCC progression and upregulate CSF2/CCL20/TNF signaling to promote IC insensitivity in HSCC, which may provide new ideas for HSCC therapy. [ABSTRACT FROM AUTHOR]

Main conclusion: AaZFP1, a C2H2-type transcription factor, was found to bind the AGT-N1-10-AGT box of AaIPPI1pro and activate the expression of AaIPPI1 involved in artemisinin biosynthesis. Artemisinin, an endoperoxide sesquiterpene lactone, is a widely used antimalarial drug isolated from Artemisia annua L. Isopentenyl pyrophosphate isomerase (AaIPPI1) catalyzes the interconversion of isopentenyl diphosphate and dimethylallyl diphosphate and is the key gene involved in the biosynthesis of artemisinin. However, the AaIPPI1 gene regulation network remains largely unknown. Here, we isolated the AaIPPI1 promoter (AaIPPI1pro) and predicted that it contains cis-elements involved in stress responses, including the TGACG motif (a methyl jasmonate-responsive element), GARE motif (a gibberellin-responsive element), ABRE (an abscisic acid-responsive element), TC-rich repeats (a stress-responsive element), and the AGT-N1–10-AGT box, which is the binding site of Cys/His2 zinc finger protein (C2H2 ZFP). The C2H2 ZFP gene AaZFP1 was discovered by screening a cDNA library using AaIPPI1pro as bait in yeast. AaZFP1 contains two conserved C2H2 regions, a nuclear localization domain (B box), a Leu-rich domain (L box), and a conserved DLN sequence (DLN box) close to its C terminus. A subcellular localization assay indicated that AaZFP1 protein is localized in the nucleus and cytoplasm. An electrophoretic mobility shift assay demonstrated that AaZFP1 binds to the AGT-N1-10-AGT box of AaIPPI1pro. A dual-luciferase assay indicated that AaZFP1 enhanced the promoter activity of AaIPPI1 in vivo. Transient overexpression of AaZFP1 in A. annua increased the expression of AaIPPI1 and the content of artemisinin. Our data demonstrated that AaZFP1 functions as a transcriptional activator that regulates the expression of AaIPPI1 by directly binding to its promoter. The present study provides insights into the transcriptional regulation of genes involved in artemisinin biosynthesis in A. annua. [ABSTRACT FROM AUTHOR]

Scholars have studied the impact of rubber particles (RPs) on the performance of the concrete and the research topics have covered all the mechanical properties and durability of normal concrete (NC). Recently, scholars have turned their research interest to the structural properties of concrete. However, there are few experimental studies on the bonding properties of RC to NC. The RPs have both positive and negative impacts on the bond performance. On one hand, RPs can reduce the shrinkage of concrete, resulting in reduced shear stress and tensile stress near the bonding boundary. On the other hand, RPs cause a reduction in the overall strength of concrete, resulting in the poor mechanical performance of the interface transition layer between the two concrete. The test results of this study show that the bonding splitting tensile strength between freshly mixed RC to aged NC first increases and then decreases with the rise of the RPs content in the RC, and the bonding splitting tensile strength reaches the peak when the RPs content is 10%. The bonding splitting tensile strength between the NC and the RC mixed with 3–5 mm RP is higher than that between the NC and the RC mixed with 1–3 mm RPs. When mixed with modified RPs, the bonding splitting tensile strength between the RC and the NC is improved. Applying an interfacial agent (a cement slurry or an epoxy) on the old concrete bonding surface can significantly improve the bonding splitting tensile strength. The results of non-repeated two-way ANOVA show that the content of the RPs and the type of the interfacial agent have significant effects on the bond splitting tensile strength, while the size and modification of the RPs have no significant effects on the bond splitting tensile strength. [ABSTRACT FROM AUTHOR]

Instability failure in rock mass engineering is closely related to expansion of joint fissures. In this study, uniaxial compression tests and acoustic emission (AE) measurements were carried out simultaneously on specimens of soft rock-like material with different fracture angles and connectivity values to better understand their influence on the deformation and failure of the material. The stress–strain curve and AE signal of fractured soft rock-like material are similar to those of intact soft rock-like; specifically, they exhibit a compaction, elastic deformation, stable fracture development, and unstable fracture development. The main differences between fractured and intact material occur during post-peak failure stage. Under the combined influence of fracture angle and connectivity, the uniaxial compressive strength of fractured soft rock-like material ( f cu ′ ) is lower than that of the intact soft rock-like material (fcu), and can be described by the relationship f cu ′ = f cu · α , where α is the strength reduction coefficient, fitted as α = 0.8228 + 0.00411 x - 0.00789 y . In this equation, x is the fracture angle ( ∘ ) and y is the fracture connectivity (%). Under uniaxial compression, the main types of secondary cracks were wing cracks and secondary coplanar cracks. The specimen with a fracture angle of 30° mainly underwent tensile failure under loading, whereas those with fracture angles of 45° and 60°mainly experienced shear failure under high-connectivity conditions (45%). [ABSTRACT FROM AUTHOR]

Hypoactive sexual desire disorder (HSDD) is one of the most common sexual complaints in women. Currently, there is an unmet need for a drug treatment for this disorder. The purpose of this study was to develop a testosterone (TS) film forming gel used for women to treat HSDD by measuring the tackiness, peel adhesion force, tensile strength, and elasticity of the formulation. Diethylene glycol monoethyl ether (Transcutol P), an efficient penetration enhancer, was added to the optimized formulation and the transdermal permeation characteristics in vitro were studied using Franz-diffusion cells. The quantitative determination of TS was performed by high-performance liquid chromatography (HPLC). After 24 h, Transcutol P at 3% had the largest cumulative amount of drug and enhancement ratio of TS of 75.14 μg/cm2 and 2.82, respectively. After the screening of film forming polymers and penetration enhancers, the optimal formulation was as follows: glycerol (1%, w/w); 12.5% sodium carboxymethylcellulose (CMC-Na) aqueous solution (0.5%, w/w); 2.5% Carbomer ethanol solution (0.5%, w/w); Transcutol P ethanol solution (3%, w/w) containing 0.5% TS; and 8% Poly vinyl alcohol (PVA) aqueous solution (30%, w/w). The optimized film forming gel had good uniformity and the release of TS in vitro was close to 100% within 24 h. In vivo studies showed the formulations had optimal area under blood drug concentration curve values in the order of 3% Transcutol P > 1% Transcutol P > 5% Transcutol P > control preparation. The formulation with 3% Transcutol P provided the highest permeation effect both in vitro and in vivo. The safety of this formulation was further evaluated with a skin irritation test. It could effectively improve the rabbit skin irritation observed with a marketed transdermal patch Androderm®. The present study provides a promising approach for the development of a novel TS film forming gel for the treatment of HSDD in women. [ABSTRACT FROM AUTHOR]

Objective: This study investigates the mismatch between the National Institutes of Health Stroke Scale (NIHSS) score and the computed tomography (CT) findings measured by the Alberta Stroke Program Early CT Score (ASPECTS) for predicting the functional outcome and safety of intravenous thrombolysis (IVT) treatment in patients with acute ischemic stroke (AIS). Methods: This prospective observational study includes patients with AIS who underwent CT imaging within 4.5 h of the onset of symptoms. Patients were divided into the NIHSS–ASPECTS mismatch (NAM)-positive and NAM-negative groups (group P and N, respectively). The clinical outcome was assessed using the Modified Rankin Scale (mRS). Safety outcomes included progression, symptomatic intracerebral hemorrhage (sICH), intracerebral hemorrhage (ICH), adverse events, clinical adverse events, and mortality. Results: A total of 208 patients were enrolled in the study. In group P, IVT treatment was associated with a good functional outcome at 3 months (p = 0.005) and 1 year (p = 0.001). A higher percentage of patients with favorable mRS (0–2) (p = 0.01) and excellent mRS (0–1) (p = 0.011) functional outcomes was obtained at 1 year in group P with IVT treatment. Group N did not benefit from the same treatment (p = 0.352 and p = 0.480 at 3 months and 1 year, respectively). There were no statistically significant differences in sICH, ICH, mortality rates, or other risks between the IVT and conventional treatment groups. Conclusion: IVT treatment is associated with a good functional outcome in patients with NAM, without increasing the risks of sICH, ICH, mortality, or other negative outcomes. NAM promises to be an easily obtained indicator for guiding the treatment decisions of AIS. [ABSTRACT FROM AUTHOR]

Background and Objectives: Huanglian-Houpo decoction (HH), which is recorded in the famous traditional Chinese medicine monograph "Puji Fang," contains two individual herbs, Huanglian (Rhizoma coptidis) and Houpo (Magnoliae officinalis cortex). It was regularly used to treat seasonal epidemic colds and influenzas in ancient China. Our laboratory discovered that HH has a significant anti-H1N1 influenza virus effect. However, no pharmacokinetic and pharmacodynamic data concerning the anti-H1N1 influenza virus activity of HH are available to date. In the current study, the concentration-time profiles of two major components of HH, berberine and magnolol, in rat plasma were investigated. Methods: An integrate pharmacokinetic approach was developed for evaluating the holistic pharmacokinetic characteristics of berberine and magnolol from HH. Additionally, the inhibition rate and levels of IFN-β in MDCK cells infected by influenza virus were analyzed. Data were calculated using 3p97 with pharmacokinetic analysis. Results: The estimated pharmacokinetic parameters were maximum plasma concentration (Cmax) 0.9086 μg/ml, area under the concentration-time curve (AUC) 347.74 μg·min/ml, and time to reach Cmax (Tmax) 64.69 min for berberine and Cmax = 0.9843 μg/ml, AUC= 450.64 μg·min/ml, Tmax = 56.86 min for magnolol, respectively. Furthermore, integrated pharmacokinetic and pharmacodynamic analysis showed that the highest plasma concentration, inhibition rate and interferon-β (IFN-β) secretion of HH first increased and then weakened over time, reaching their peaks at 60 min. The plasma concentration of HH is directly related to the anti-influenza virus effect. Conclusion: The results indicated that berberine and magnolol are the main active ingredients of HH related to its anti-influenza virus effect, which is related to the improvement of IFN-β secretion. [ABSTRACT FROM AUTHOR]

Purpose: To determine the role of vaginal microbiota in the efficacy of cervical cerclage in obstetric outcomes of twin pregnancies. Methods: This retrospective study enrolled 68 twin pregnant women diagnosed with cervical incompetence (CIC) and 68 twin pregnancies without CIC. The CIC group was further divided into two subgroups: cerclage group (n = 51) and non-cerclage group (n = 17), according to whether cervical cerclage was performed in the second trimester. Data of vaginal microbiota and obstetric outcomes were collected and compared. Results: Cervical incompetence had harmful effect on both pregnancy outcomes and vaginal microecology, characterized by earlier gestational week at delivery (30.3 ± 5.6 vs 35.6 ± 1.1, P < 0.001), a lower birth weight of newborns (OR 0.40; 95% CI 0.22–0.74), a higher vaginal pH value (OR 0.11; 95% CI 0.04–0.30) and a lower abundance of Lactobacillus (OR 0.34; 95% CI 0.17–0.70). In addition, compared with the vaginal microbiota after cerclage, less normal diversity of bacterial flora (OR 0.35; 95% CI 0.12–1.01), less Lactobacillus (OR 0.40; 95% CI 0.18–0.91) and more Gardnerellavaginalis (OR 18.92; 95% CI 2.38–150.35) appeared before cerclage. Besides, the unhealthy vaginal environment also had an unfavorable influence on the neonatal outcomes, increased neonatal mortality rate was observed in the group of vaginal pH > 4.5 (P < 0.05). Fortunately, compared with the non-cerclage group, the cerclage group had a longer interval from diagnosis to delivery (≥ 8 weeks) and more of the newborns' birth weight were not less than 1500 g (P < 0.05). Conclusion: A healthy vaginal environment is essential to improve the obstetric outcome for twin pregnancies with cervical cerclage. [ABSTRACT FROM AUTHOR]

Quantifying predictive uncertainty in deep neural networks is a challenging and yet unsolved problem. Existing quantification approaches can be categorized into two lines. Bayesian methods provide a complete uncertainty quantification theory but are often not scalable to large-scale models. Along another line, non-Bayesian methods have good scalability and can quantify uncertainty with high quality. The most remarkable idea in this line is Deep Ensemble, but it is limited in practice due to its expensive computational cost. Thus, we propose HatchEnsemble to improve the efficiency and practicality of Deep Ensemble. The main idea is to use function-preserving transformations, ensuring HatchNets to inherit the knowledge learned by a single model called SeedNet. This process is called hatching, and HatchNet can be obtained by continuously widening the SeedNet. Based on our method, two different hatches are proposed, respectively, for ensembling the same and different architecture networks. To ensure the diversity of models, we also add random noises to parameters during hatching. Experiments on both clean and corrupted datasets show that HatchEnsemble can give a competitive prediction performance and better-calibrated uncertainty quantification in a shorter time compared with baselines. [ABSTRACT FROM AUTHOR]

Rubberized concrete is an environmentally friendly building material that mixes rubber particles from old automobile tires into normal concrete in place of fine aggregate. The addition of rubber particles can improve the abrasion resistance of normal concrete observably. It has a good application prospect in hydraulic engineering, especially in the concrete building parts with high abrasion resistance. However, there are few experimental studies on the abrasion resistance of rubberized concrete, and the influence law and mechanism of rubber particles on the abrasion resistance of concrete are not understood. In this paper, the abrasion resistance of rubberized concrete is studied using the underwater-steel-ball method. The results show that rubber particles increase the slump of concrete mixtures. The abrasion resistance of rubberized concrete increases significantly with increasing rubber particle content, whereas the compressive strength decreases linearly. For the same rubber particle size and content, the abrasion resistance of rubberized concrete positively correlates with compressive strength and larger rubber particles significantly improve the abrasion resistance. Rubber particle content is the factor that most strongly affects abrasion resistance of rubberized concrete, followed by the compressive strength. Rubber particle pretreatment methods of NaOH + KH570 can significantly improve the abrasion resistance of rubberized concrete. [ABSTRACT FROM AUTHOR]

Purpose: The aim of the study is to identify a reliable gene panel to predict the prognosis of HNSCC patients by integrated genomic analysis. Methods: Co-expression gene networks were constructed by WGCNA using GSE113282 gene expression profile. The biological functional investigation was performed by GO and KEGG function enrichment analysis. The hub gene module was screened by PPI. The prognostic gene panel was established by Lasso regression analysis, and further progression-free survival (PFS) analysis was validated by Kaplan–Meier survival analysis using GSE102995 data. Results: We identified 195 genes associated with the overall survival (OS) status (correlation coefficients: − 0.42, and p value: 2e−05) by WGCNA. These genes were enriched in immune-related cytokines and pathways analyzed by GO and KEGG. Among the 195 genes, the module (42 genes) with the highest score was screened by PPI. A novel seven-gene predictive panel (CD19, CD40LG, CD5, CXCR6, FPR2, NCAM1, and SELL) was established by Lasso regression analysis, and the area under ROC curve (AUC) for 3-year OS status was 0.8298 and 0.7571, respectively, in the training set and the test set. The PFS time of the low-risk patients was significantly longer than the high-risk patients (p < 0.0001; log-rank test) by further validation using GSE102995 data. Conclusion: The seven-gene panel may serve as a reliable predictive tool for HNSCC patients treated with platinum-based radio (chemo) therapy, and may be potential therapeutic targets for HNSCC patients. [ABSTRACT FROM AUTHOR]

Summary: Neuroblastoma (NB) is a common tumor in children, usually in the retroperitoneum. After various treatments, low- and intermediate-risk patients have achieved good results, but the prognosis of high-risk patients is still very poor. Therefore, it is necessary to find new effective targets for the treatment of high-risk patients. In this study, comprehensive bioinformatics analysis was used to identify the differentially expressed genes (DEG and DEM) between high-risk patients and non-high-risk patients, and it was identified that ADRB2 may affect the survival status of high-risk patients due to miR -30a-5p regulation. The GSE49710, GSE73517, and GSE121513 datasets were downloaded from the Gene Expression Synthesis (GEO) database, and DEG and DEM were selected. Then, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were applied to the selected DEGs. The STRING database and Cytoscape software were used to construct protein-protein interaction (PPI) networks and perform modular analysis of the DEGs. The TARGET data set containing information on overall survival days were used for the prognostic analysis of central genes. We identified a total of 255 DEGs from GSE49710 and GSE73517, and 193 DEMs from GSE121513. We identified the 5 most important central genes from the PPI network, performed a prognostic analysis in the target data set, and verified their expression using RT-qPCR to select the most important ADRB2 gene to predict miRNA. Integrating the differential miRNA predicted by miRDB and miRSystem and GSE121513 between the targeted miRNA and the prognosis, miR-30a-5p was finally identified as the targeted miRNA of ADRB2. [ABSTRACT FROM AUTHOR]

The outbreak of coronavirus disease 2019 (COVID-19) is a global health emergency. Various omics results have been reported for COVID-19, but the molecular hallmarks of COVID-19, especially in those patients without comorbidities, have not been fully investigated. Here we collect blood samples from 231 COVID-19 patients, prefiltered to exclude those with selected comorbidities, yet with symptoms ranging from asymptomatic to critically ill. Using integrative analysis of genomic, transcriptomic, proteomic, metabolomic and lipidomic profiles, we report a trans-omics landscape for COVID-19. Our analyses find neutrophils heterogeneity between asymptomatic and critically ill patients. Meanwhile, neutrophils over-activation, arginine depletion and tryptophan metabolites accumulation correlate with T cell dysfunction in critical patients. Our multi-omics data and characterization of peripheral blood from COVID-19 patients may thus help provide clues regarding pathophysiology of and potential therapeutic strategies for COVID-19. COVID-19 is a critical public health threat, but molecular characterizations of patients' immunity is still lacking. Here the authors collected blood from patients with various disease severity, and prefiltered to exclude selected comorbidity, to obtain genomic, transcriptomic, proteomic, metabolomic and lipidomic profiles to report a trans-omics landscape. [ABSTRACT FROM AUTHOR]

To determine the factors predicting the probability of severe postpartum hemorrhage (SPPH) in women undergoing repeat cesarean delivery (RCD). This multicenter, retrospective cohort study involved women who underwent RCD from January 2017 to December 2017, in 11 public tertiary hospitals within 7 provinces of China. The all-variables model and the multivariable logistic regression model (pre-operative, operative and simple model) were developed to estimate the probability of SPPH in development data and external validated in validation data. Discrimination and calibration were evaluated and clinical impact was determined by decision curve analysis. The study consisted of 11,074 women undergoing RCD. 278 (2.5%) women experienced SPPH. The pre-operative simple model including 9 pre-operative features, the operative simple model including 4 pre-operative and 2 intraoperative features and simple model including only 4 closely related pre-operative features showed AUC 0.888, 0.864 and 0.858 in development data and 0.921, 0.928 and 0.925 in validation data, respectively. Nomograms were developed based on predictive models for SPPH. Predictive tools based on clinical characteristics can be used to estimate the probability of SPPH in patients undergoing RCD and help to allow better preparation and management of these patients by using a multidisciplinary approach of cesarean delivery for obstetrician. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the performance of a knowledge-based RapidPlan, for optimisation of intensity-modulated proton therapy (IMPT) plans applied to hepatocellular cancer (HCC) patients. Methods: A cohort of 65 patients was retrospectively selected: 50 were used to "train" the model, while the remaining 15 provided independent validation. The performance of the RapidPlan model was benchmarked against manual optimisation and was also compared to volumetric modulated arc therapy (RapidArc) photon plans. A subanalysis appraised the performance of the RapidPlan model applied to patients with lesions ≤300 cm3 or larger. Quantitative assessment was based on several metrics derived from the constraints of the NRG-GI003 clinical trial. Results: There was an equivalence between manual plans and RapidPlan-optimised IMPT plans, which outperformed the RapidArc plans. The planning dose–volume objectives were met on average for all structures except for D0.5cm3 ≤30 Gy in the bowels. Limiting the results to the class-solution proton plans (all values in Gy), the data for manual plans vs RapidPlan-based IMPT plans, respectively, showed the following: D99% to the target of 47.5 ± 1.4 vs 47.2 ± 1.2; for organs at risk, the mean dose to the healthy liver was 6.7 ± 3.6 vs 6.7 ± 3.7; the mean dose to the kidneys was 0.2 ± 0.5 vs 0.1 ± 0.2; D0.5cm3 for the bowels was 33.4 ± 16.4 vs 30.2 ± 16.0; for the stomach was 17.9 ± 19.9 vs 14.9 ± 18.8; for the oesophagus was 17.9 ± 15.1 vs 14.9 ± 13.9; for the spinal cord was 0.5 ± 1.6 vs 0.2 ± 0.7. The model performed similarly for cases with small or large lesions. Conclusion: A knowledge-based RapidPlan model was trained and validated for IMPT. The results demonstrate that RapidPlan can be trained adequately for IMPT in HCC. The quality of the RapidPlan-based plans is at least equivalent compared to what is achievable with manual planning. RapidPlan also confirmed the potential to optimise the quality of the proton therapy results, thus reducing the impact of operator planning skills on patient results. [ABSTRACT FROM AUTHOR]

Purpose: Critically ill COVID-19 patients have significantly increased risk of death. Although several circulating biomarkers are thought to be related to COVID-19 severity, few studies have focused on the characteristics of critically ill patients with different outcomes. The objective of this study was to perform a longitudinal investigation of the potential mechanisms affecting the prognosis of critically ill COVID-19 patients. Methods: In addition to clinical data, 113 whole blood samples and 85 serum samples were collected from 33 severe and critical COVID-19 patients without selected comorbidities. Multi-omics analysis was then performed using longitudinal samples. Results: Obvious transcriptional transitions were more frequent in critical survivors than in critical non-survivors, indicating that phase transition may be related to survival. Based on analysis of differentially expressed genes during transition, the erythrocyte differentiation pathway was significantly enriched. Furthermore, clinical data indicated that red blood cell counts showed greater fluctuation in survivors than in non-survivors. Moreover, declining red blood cell counts and hemoglobin levels were validated as prognostic markers of poor outcome in an independent cohort of 114 critical COVID-19 patients. Protein–metabolite–lipid network analysis indicated that tryptophan metabolism and melatonin may contribute to molecular transitions in critical COVID-19 patients with different outcomes. Conclusions: This study systematically and comprehensively depicted the longitudinal hallmarks of critical COVID-19 patients and indicated that multi-omics transition may impact the prognosis. Take home message: Frequent transcriptional phase transitions may contribute to outcome in critically ill COVID-19 patients. Furthermore, fluctuation in red blood cell and hemoglobin levels may relate to poor prognosis. The biological function of melatonin was suppressed in COVID-19 non-survivors, which may provide a potential theoretical basis for clinical administration. [ABSTRACT FROM AUTHOR]

Melanoma is a skin cancer with great metastatic potential, which is responsible for the major deaths in skin cancer. Although the prognosis of melanoma patients has been improved with the comprehensive treatment, for patients with metastasis, the complexity and heterogeneity of diffuse diseases make prognosis prediction and systematic treatment difficult and ineffective. Therefore, we established a novel personalized immune-related gene pairs index (IRGPI) to predict the prognosis of patients with metastatic melanoma, which was conducive to provide new insights into clinical decision-making and prognostic monitoring for metastatic melanoma. Through complex analysis and filtering, we identified 24 immune-related gene pairs to build the model and obtained the optimal cut-off value from receiver operating characteristic curves, which divided the patients into high and low immune-risk groups. Meantime, the Kaplan–Meier analysis, Cox regression analysis and subgroup analysis showed that IRGPI had excellent prognostic value. Furthermore, IRGPI was shown that was closely associated with immune system in the subsequent tumor microenvironment analysis and gene set enrichment analysis. In addition, we broken through the data processing limitations of traditional researches in different platforms through the application of gene pairs, which would provide great credibility for our model. We believe that our research would provide a new perspective for clinical decision-making and prognostic monitoring in metastatic melanoma. [ABSTRACT FROM AUTHOR]