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BackgroundTo explore the safety, efficacy, and survival benefits of laparoscopic digestive tract nutrition reconstruction (LDTNR) combined with conversion therapy in patients with unresectable gastric cancer with obstruction.MethodsThe clinical data of patients with unresectable gastric cancer with obstruction who was treated in Fujian Provincial Hospital from January 2016 to December 2019, were analyzed. LDTNR was performed according to the type and degree of obstruction. All patients received the epirubicin + oxaliplatin + capecitabine regimen as conversion therapy.ResultsThirty-seven patients with unresectable obstructive gastric cancer underwent LDTNR, while thirty-three patients received chemotherapy only. In LDTNR group patients, the proportion of nutritional risks gradually decreased, the rate of severe malnutrition decreased, the proportion of neutrophil-lymphocyte ratio (NLR)

A new species of Oreocharis, O. guangwushanensis from the Sichuan Province of south-western China, is described and illustrated here. This new species has a pink corolla that is different from other species of Oreocharis in southwest China and, although it is morphologically similar to O. ronganensis and O. reticuliflora, it has significant differences in the colour and shape of the corolla, the apex of the corolla limb, shape and indumentum of the filaments and a shorter pistil. A detailed description, colour photographs, distribution and habitat, as well as the IUCN conservation status, are also provided.

BackgroundIntracorporeal anastomosis (IA) is a difficult but popular anastomotic approach for reconstruction of digestive tract after laparoscopic right hemicolectomy, which may reduce some limitations faced during extracorporeal anastomosis (EA).MethodsA retrospective review of 78 patients who underwent laparoscopic right hemicolectomy by a veteran surgeon in a high-volume public tertiary hospital, including 50 patients with IA and 28 patients with EA. The intraoperative-related factors and short-term results of the two anastomotic approaches were compared.ResultsThere was no significant difference in demographics and clinical characteristics between the two groups (P>0.05). The intraoperative blood loss was less (P=0.010) and the incision length was shorter (P

To improve the network switching performance and efficiency of mobile phone terminals and establish an efficient mobile communication network connection, this paper constructs the SDN+MPTCP+CP (Software Defined Network, Multi-Path TCP, and Mobile Terminal) mobile communication network model and designs a network switching algorithm with a preselected available access point name (APN) based on the potential game method. The constructed network model integrates a 5G mobile communication network, satellite communication, the SDN network, and the MPTCP multi-way communication technology. APN access point is preselected by using Kalman filtering theory, and dual problems are resolved with the Lagrange function. To determine the MPTCP sub-flow transmission path, the differential derivative calculation is introduced. The performance of the network switching strategy is evaluated based on the Jacobian matrix. Then, the game coefficient is designed, and the game function is calculated. A potential game balance point is found, and an updating strategy is formulated to determine the best APN access point. The simulation network model is constructed, and the parameters of the performance evaluation are defined to find the performance comprehensively. The experimental results demonstrated the extreme reliability, stability, and compatibility of the proposed algorithm.

ObjectiveUltrasound imaging has been widely used in breast cancer screening. Recently, ultrasound super-resolution imaging (SRI) has shown the capability to break the diffraction limit to display microvasculature. However, the application of SRI on differential diagnosis of breast masses remains unknown. Therefore, this study aims to evaluate the feasibility and clinical value of SRI for visualizing microvasculature and differential diagnosis of breast masses.MethodsB mode, color-Doppler flow imaging (CDFI) and contrast-enhanced ultrasound (CEUS) images of 46 patients were collected respectively. SRI were generated by localizations of each possible contrast signals. Micro-vessel density (MVD) and microvascular flow rate (MFR) were calculated from SRI and time to peak (TTP), peak intensity (PI) and area under the curve (AUC) were obtained by quantitative analysis of CEUS images respectively. Pathological results were considered as the gold standard. Independent chi-square test and multivariate logistic regression analysis were performed using these parameters to examine the correlation.ResultsThe results showed that SRI technique could be successfully applied on breast masses and display microvasculature at a significantly higher resolution than the conventional CDFI and CEUS images. The results showed that the PI, AUC, MVD and MFR of malignant breast masses were significantly higher than those of benign breast masses, while TTP was significantly lower than that of benign breast masses. Among all five parameters, MVD showed the highest positive correlation with the malignancy of breast masses.ConclusionsSRI is able to successfully display the microvasculature of breast masses. Compared with CDFI and CEUS, SRI can provide additional morphological and functional information for breast masses. MVD has a great potential in assisting the differential diagnosis of breast masses as an important imaging marker.

ObjectiveUltrasound imaging provides a fast and safe examination of thyroid nodules. Recently, the introduction of super-resolution imaging technique shows the capability of breaking the Ultrasound diffraction limit in imaging the micro-vessels. The aim of this study was to evaluate its feasibility and value for the differentiation of thyroid nodules.MethodsIn this study, B-mode, contrast-enhanced ultrasound, and color Doppler flow imaging examinations were performed on thyroid nodules in 24 patients. Super-resolution imaging was performed to visualize the microvasculature with finer details. Microvascular flow rate (MFR) and micro-vessel density (MVD) within thyroid nodules were computed. The MFR and MVD were used to differentiate the benign and malignant thyroid nodules with pathological results as a gold standard.ResultsSuper-resolution imaging (SRI) technique can be successfully applied on human thyroid nodules to visualize the microvasculature with finer details and obtain the useful clinical information MVD and MFR to help differential diagnosis. The results suggested that the mean value of the MFR within benign thyroid nodule was 16.76 ± 6.82 mm/s whereas that within malignant thyroid was 9.86 ± 4.54 mm/s. The mean value of the MVD within benign thyroid was 0.78 while the value for malignant thyroid region was 0.59. MFR and MVD within the benign thyroid nodules were significantly higher than those within the malignant thyroid nodules respectively (p < 0.01).ConclusionsThis study demonstrates the feasibility of ultrasound super-resolution imaging to show micro-vessels of human thyroid nodules via a clinical ultrasound platform. The important imaging markers, such as MVD and MFR, can be derived from SRI to provide more useful clinical information. It has the potential to be a new tool for aiding differential diagnosis of thyroid nodules.

Krabbe disease (KD), also known as globoid cell leukodystrophy, is a rare autosomal recessive condition caused by mutations in the galactocerebrosidase (GALC) gene. KD is more common in infants and young children than in adults. We reported the case of an adult-onset KD presenting with progressive myoclonic epilepsy (PME) and cortical lesions mimicking mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome. The whole-exome sequencing (WES) identified a pathogenic homozygous missense mutation of the GALC gene. Parents of the patient were heterozygous for the mutation. The clinical, electrophysiological, and radiological data of the patient were retrospectively analyzed. The patient was a 24-year-old woman presenting with generalized seizures, progressive cognitive decline, psychiatric symptoms, gait ataxia, and action-induced myoclonus. The brain magnetic resonance imaging (MRI) revealed a right occipital cortical ribbon sign without any other damage. This single case expands the clinical phenotypes of adult-onset KD.

Adsorption is a fundamentally important process but challenging to quantify, especially at the nanoscale. Here, the authors map the adsorption affinity and cooperativity of various ligands on single gold nanoparticles and discover adsorption crossover behaviors between different facets, leading to a strategy to control particle shape.

Abstract Synaptic loss is an early and clinically relevant feature of many neurodegenerative diseases. Here we assess three adults at risk of frontotemporal dementia from C9orf72 mutation, using [11C]UCB‐J PET to quantify synaptic density in comparison with 19 healthy controls and one symptomatic patient with behavioural variant frontotemporal dementia. The three pre‐symptomatic C9orf72 carriers showed reduced synaptic density in the thalamus compared to controls, and there was an additional extensive synaptic loss in frontotemporal regions of the symptomatic patient. [11C]UCB‐J PET may facilitate early, pre‐symptomatic assessment, monitoring of disease progression and evaluation of new preventive treatment strategies for frontotemporal dementia.

Abstract Background Primary adrenal insufficiency (PAI) is life-threatening, and a definitive aetiological diagnosis is essential for management and prognostication. We conducted this study to investigate the genetic aetiologies of PAI in South China and explore their clinical features. Methods Seventy children were enrolled in this cross-sectional study. Clinical information was collected, and combined genetic tests were performed according to the children’s manifestations. Statistical analysis was performed among the different groups. In silico or in vitro experiments were applied to determine the pathogenicity of novel variants. Results Among the 70 children, 84.3% (59/70) were diagnosed with congenital adrenal hyperplasia (CAH), and 21-hydroxylase deficiency (21-OHD) was genetically confirmed in 91.5% of these cases. Salt wasting (SW), simple virilization (SV), and non-classic (NC) CAH accounted for 66.1% (39/59), 30.5% (18/59), and 3.4% (2/59) of the cases, respectively. The 17-hydroxyprogesterone (17-OHP) and testosterone (TES) levels were significantly higher in children with SW than with SV. The 17-OHP and cortisol levels in female SW patients were significantly higher than those in males. The 17-OHP, cortisol, dehydroepiandrosterone (DHEAS) and TES levels in female SW patients were significantly higher than those in female SV patients. Additionally, 72.7% (8/11) of uncharacterized PAI patients had positive genetic findings. Among all the patients, two novel variants in the CYP21A2 gene (c.833dupT and c.651 + 2T > G) were found. A microdeletion (Xp21.2–21.3) and five novel variants, including 2 in the NR0B1 gene (c.323–324CG > GA and c.1231_1234delCTCA), 2 in the AAAS gene (c.399 + 1G > A and c.250delT) and 1 in the NNT gene (c.2274delT), were detected. The novel variant c.399 + 1G > A in the AAAS gene was further confirmed to lead to exon 4 skipping during mRNA transcription and produce a truncated ALADIN protein. Conclusions We found ethnicity-based differences in the CYP21A2 gene variant spectrum among different study populations. Female 21-OHD patients tended to have higher 17-OHP and TES levels, which warrants caution in relation to the effects of virilization. Novel gene variants detected in the CYP21A2, NR0B1, AAAS and NNT genes expanded the genetic spectrum of PAI, however, further improvement of genetic testing tools beyond our protocol are still needed to uncover the complete aetiology of PAI in children.

Purpose: To characterize our experience and the disease control and toxicity of proton therapy (PT) for patients with head and neck cancer (HNC). Patients and Methods: Clinical outcomes for patients with HNC treated with PT at our institution were prospectively collected in 2 institutional review board–approved prospective studies. Descriptive statistics were used to summarize patient characteristics and outcomes. Overall survival, local-regional control, and disease-free survival were estimated by the Kaplan-Meier method. Treatment-related toxicities were recorded according to the Common Terminology Criteria for Adverse Events (version 4.03) scale. Results: The cohort consisted of 573 patients treated from February 2006 to June 2018. Median patient age was 61 years. Oropharynx (33.3%; n = 191), paranasal sinus (11%; n = 63), and periorbital tissues (11%; n = 62) were the most common primary sites. Patients with T3/T4 or recurrent disease comprised 46% (n = 262) of the cohort. The intent of PT was definitive in 53% (n = 303), postoperative in 37% (n = 211), and reirradiation in 10% (n = 59). Median dose was 66 Gy (radiobiological equivalent). Regarding systemic therapy, 43% had received concurrent (n = 244), 3% induction (n = 19), and 15% (n = 86) had both. At a median follow-up of 2.4 years, 88 patients (15%) had died and 127 (22%) developed disease recurrence. The overall survival, local-regional control, and disease-free survival at 2 and 5 years were, respectively, 87% and 75%, 87% and 78%, and 74% and 63%. Maximum toxicity (acute or late) was grade 3 in 293 patients (51%), grade 2 in 234 patients (41%), and grade 1 in 31 patients (5%). There were 381 acute grade 3 and 190 late grade 3 unique toxicities across 212 (37%) and 150 (26%) patients, respectively. There were 3 late-grade 4 events across 2 patients (0.3%), 2 (0.3%) acute-grade 5, and no (0%) late-grade 5 events. Conclusions: The overall results from this prospective study of our initial decade of experience with PT for HNC show favorable disease control and toxicity outcomes in a multidisease-site cohort and provide a reference benchmark for future comparison and study.

Purpose: To report patient-reported outcomes (PROs) derived from the Functional Assessment of Cancer Therapy-Head and Neck (FACT-HN) tool, in patients with oropharynx cancer (OPC) treated with intensity-modulated proton therapy (IMPT) in the context of first-course irradiation. Materials and Methods: Patients with locally advanced OPC treated with radical IMPT between 2011 and 2018 were included in a prospective registry. FACT-HN scores were measured serially during and 24 months following IMPT. PRO changes in the FACT-HN scores over time were assessed with mixed-model analysis. Results: Fifty-seven patients met inclusion criteria. Median age was 60 years (range, 41-84), and 91% had human papillomavirus-associated disease. In total, 28% received induction chemotherapy and 68% had concurrent chemotherapy. Compliance to FACT-HN questionnaire completion was 59%, 48%, and 42% at 6, 12, and 24 months after treatment, respectively. The mean FACT-General (G), FACT-Total, and FACT-Trial Outcome Index (TOI) score changes were statistically and clinically significant relative to baseline from week 3 of treatment up to week 2 after treatment. Nadir was reached at week 6 of treatment for all scores, with maximum scores dropping by 15%, 20%, and 39% compared to baseline for FACT-G, FACT-Total, and FACT-TOI, respectively. Subdomain scores of physical well-being, functional well-being, and head and neck additional concerns decreased from baseline during treatment and returned to baseline at week 4 after treatment. Conclusions: IMPT was associated with a favorable PRO trajectory, characterized by an acute decline followed by rapid recovery to baseline. This study establishes the expected acute, subacute, and chronic trajectory of PROs for patients undergoing IMPT for OPC.

The SARS-CoV-2 spike protein contains a multi-basic cleavage site. Here, the authors show how this multi-basic cleavage site affects entry of SARS-CoV-2 into cells and transmission in the hamster model and identify host factors affecting entry of SARS-CoV-2 in a genome-wide CRISPR screen.

Daminozide, a plant growth regulator, is an effective inhibitor of the Jumonji domain-containing protein (JMJD) histone demethylase. Herein, four ruthenium(II)/rhenium(I)-daminozide conjugates, with molecular formulas [Ru(N-N)2bpy(4-CH2OH-4′-CH2O-daminozide)](PF6)2 (Ru-1/Ru-2) (N-N = 1,10-phenanthroline (phen, in Ru-1) and 4,7-diphenyl-1,10-phenanthroline (DIP, in Ru-2)) and Re(N-N)(CO)3(PyCH2O-daminozide) (Re-1/Re-2) (Py = pyridine, N-N = phen (in Re-1) and DIP (in Re-2)), were synthesized and characterized. Among these complexes, Ru-2 and Re-2 exhibited higher cytotoxicity against tumor cells than cisplatin. Upregulation of H3K9Me3 expression level was found in human cervical cancer cells (HeLa) treated with Ru-2 and Re-2, indicating that these two complexes can inhibit the activity of JMJD histone demethylase. Further investigation revealed that Re-2 can selectively accumulate in the mitochondria of HeLa cells. Both Ru-2 and Re-2 can cause mitochondrial damage, induce apoptosis, and inhibit cell migration and colony formation of HeLa cells. Overall, these complexes exhibit multiple anticancer functions, including inhibiting JMJD, inducing apoptosis, and inhibiting cell invasion, making them promising candidates for anticancer drugs.

BackgroundData are limited concerning the survival outcomes of patients with gastric outlet obstruction (GOO) caused by advanced gastric cancers according to laparoscopic gastrojejunostomy (LGJ) combined with multimodality therapy (MMT). Therefore, the purpose of this study was to examine the feasibility and efficacy of these therapies.MethodsThis single-centered, retrospective analysis included data of 184 patients with GOO due to advanced gastric cancer (AGC). Treatment models were: laparoscopic gastrojejunostomy combined with multimodality therapy (LGJ+MMT), endoscopic metal stent placement combined with multimodality therapy (EMSP+MMT), and multimodality therapy (MMT).ResultsImproved oral intake, better nutritional indices, and better response to chemotherapy were observed in the LGJ+MMT group. Subsequent gastrectomy was performed in 43 (61.4%) patients in the LGJ+MMT group, 23 (37.7%) in the EMSP+MMT group, and 11 (20.8%) in the MMT group (P

The spatiotemporal patterns of urban expansion have attracted worldwide attention and have been generalized into several prevalent hypotheses, such as the diffusion–coalescence hypothesis and the three-growth-type hypothesis. Although many studies have examined the applicability of these hypotheses, long-term research and evidence are still lacking. This study incorporated a compiled dataset of multisource remote sensing images and historical maps covering nine snapshots of the urban built-up area from 1914 to 2018 to monitor the urban expansion process in Hangzhou, China. A fractal analysis of the area–radius relationship was employed for areal demarcation to explore the heterogenous patterns across different intra-city spatial extents. The results show that (1) Hangzhou has experienced a turbulent period of primitive urbanization in the pre-reform era and a consecutive period of market-oriented urbanization after the economic reform; (2) the urban expansion pattern characterized by landscape metrics demonstrates the existence of multiple alternations between diffusion and coalescence phases with peculiarities across different intra-city spatial extents; (3) the analysis of urban growth types documents a consistent predominance of edge-expansion with wax and wane between infilling and leapfrogging; and (4) institutional reform, industrial development, and administrative division adjustment are the main drivers of urban expansion in Hangzhou. Our findings suggest that effective planning policies need to be raised to curb urban sprawl. Differentiated planning strategies should be proposed to accommodate unique conditions in different urban subregions. The integrated-analysis approach based on multisource remote sensing images and historical maps establishes a feasible pathway for long-term urban research.

Uveal melanoma is the most common primary intraocular tumor with a poor prognosis. Currently, treatment for UVM is limited, and the development of drug resistance and tumor recurrence are common. Therefore, it is important to identify new prognostic biomarkers of UVM and explore their role in the tumor microenvironment. Pyroptosis is a way of cell programmed death, and related research is in full throttle. However, the role of pyroptosis in UVM is unclear. In this study, we constructed the prognosis model of pyroptosis-related genes of UVM. This model can accurately guide the prognosis of UVM, and different groups differ in immune infiltration. We further verified our results in cell experiments. To some extent, our study can provide new ideas for the diagnosis and treatment of UVM.

ObjectiveThis study aimed to explore the value of elasticity score (ES) and strain ratio (SR) combined with conventional ultrasound in distinguishing benign and malignant breast masses and reducing biopsy of BI-RADS (Breast Imaging Reporting and Data System) 4a lesions.MethodsThis prospective, multicenter study included 910 patients from nine different hospitals. The acquisition and analysis of conventional ultrasound and strain elastography (SE) were obtained by radiologists with more than 5 years of experience in breast ultrasound imaging. The diagnostic sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under curve (AUC) of conventional ultrasound alone and combined tests with ES and/or SR were calculated and compared.ResultsThe optimal cutoff value of SR for differentiating benign from malignant masses was 2.27, with a sensitivity of 60.2% and a specificity of 84.8%. When combined with ES and SR, the AUC of the new BI-RADS classification increased from 0.733 to 0.824 (p < 0.001); the specificity increased from 48.1% to 68.5% (p < 0.001) without a decrease in the sensitivity (98.5% vs. 96.4%, p = 0.065); and the PPV increased from 52.2% to 63.7% (p < 0.001) without a loss in the NPV (98.2% vs. 97.1%, p = 0.327). All three combinations of conventional ultrasound, ES, and SR could reduce the biopsy rate of category 4a lesions without reducing the malignant rate of biopsy (from 100% to 68.3%, 34.9%, and 50.4%, respectively, all p < 0.001).ConclusionsSE can be used as a useful and non-invasive additional method to improve the diagnostic performance of conventional ultrasound by increasing AUC and specificity and reducing the unnecessary biopsy of BI-RADS 4a lesions.

Introduction: Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer still lacking effective treatment options. Chemotherapy in combination with immunotherapy can restrict tumor progression and repolarize the tumor microenvironment towards an anti-tumor milieu, improving clinical outcome in TNBC patients. The chemotherapeutic drug paclitaxel has been shown to induce immunogenic cell death (ICD), whereas inhibitors of the indoleamine 2,3-dioxygenase 1 (IDO1) enzyme, whose expression is shared in immune regulatory and tumor cells, have been revealed to enhance the anti-tumor immune response. However, poor bioavailability and pharmacokinetics, off target effects and hurdles in achieving therapeutic drug concentrations at the target tissue often limit the effectiveness of combination therapies. Methods: This work describes the development of novel biomimetic and carrier free nanobinders (NBs) loaded with both paclitaxel and the IDO1 inhibitor NLG919 in the form of bioresponsive and biomimetic prodrugs. A fine tuning of the preparation conditions allowed to identify NB@5 as the most suitable nanoformulation in terms of reproducibility, stability and in vitro effectiveness. Results and discussion: Our data show that NB@5 effectively binds to HSA in cellfree experiments, demonstrating its protective role in the controlled release of drugs and suggesting the potential to exploit the protein as the endogenous vehicle for targeted delivery to the tumor site. Our study successfully proves that the drugs encapsulated within the NBs are preferentially released under the altered redox conditions commonly found in the tumor microenvironment, thereby inducing cell death, promoting ICD, and inhibiting IDO1. [ABSTRACT FROM AUTHOR]

Abstract Background Focal segmental lesions (FSLs) are not uncommon in idiopathic membranous nephropathy (IMN). The reported percentage of IMN patients with focal segmental glomerulosclerosis (FSGS) lesions varies widely between studies. The objective of this study was to differentiate atypical FSL (aFSL) from typical FSGS in IMN and to analyse the clinicopathological predictors of primary outcome of IMN patients. Methods A total of 716 patients with biopsy-proven IMN between January 1, 2007 and December 31, 2017 were enrolled in the study. An atypical focal segmental lesion was defined as pure synechia, segmental hyperplasia of podocytes or thickening of the GBM accompanied by proliferation of the mesangial matrix, and absence of typical FSGS. The patients were divided into three groups: patients without FSL (FSL−), patients with typical FSGS (FSGS+), and patients with aFSL (aFSL+).The primary outcome was a 50% decline in the initial estimated glomerular filtration rate or end-stage renal disease (ESRD) incidence. Secondary outcomes included all-cause death and ESRD. Results FSGS was present in 174 patients, while aFSL was noted in 161 patients. Systolic blood pressure was higher in both aFSL+ group and FSGS+ groups compared with the FSL− group. IMN patients without FSL and with aFSL had lower serum creatinine levels than IMN patients with FSGS. Both the FSGS+ and aFSL+ groups had higher levels of proteinuria and lower albumin levels than the FSL− group. Renal tissue lesions, including tubulointerstitial fibrosis, glomerular obsolescence, and vascular sclerosis were significantly more severe in the FSGS+ group. Cox multivariate analysis showed that older age ≥ 60 years, eGFR

Abstract Background During maize early kernel development, the dramatic transcriptional reprogramming determines the rate of developmental progression, and phytohormone plays critical role in these important processes. To investigate the phytohormone levels and transcriptome reprogramming profiles during maize early kernel development, two maize inbreds with similar genetic background but different mature kernel sizes (ILa and ILb) were used. Results The levels of indole-3-acetic acid (IAA) were increased continuously in maize kernels from 5 days after pollination (DAP) to 10 DAP. ILa had smaller mature kernels than ILb, and ILa kernels had significantly lower IAA levels and significantly higher SA levels than ILb at 10 DAP. The different phytohormone profiles correlated with different transcriptional reprogramming in the two kernels. The global transcriptomes in ILa and ILb kernels were strikingly different at 5 DAP, and their differences peaked at 8 DAP. Functional analysis showed that the biggest transcriptome difference between the two kernels is those response to biotic and abiotic stresses. Further analyses indicated that the start of dramatic transcriptional reprogramming and the onset of significantly enriched functional categories, especially the “plant hormone signal transduction” and “starch and sucrose metabolism”, was earlier in ILa than in ILb, whereas more significant enrichment of those functional categories occurred at later stage of kernel development in ILb. Conclusions These results indicate that later onset of the significantly enriched functional categories, coincide with their stronger activities at a later developmental stage and higher IAA level, are necessary for young kernels to undergo longer mitotic activity and finally develop a larger kernel size. The different onset times and complex interactions of the important functional categories, especially phytohormone signal, and carbohydrate metabolism, form the most important molecular regulators mediating maize early kernel development.

Artificial intelligence (AI) has invaded our daily lives, and in the last decade, there have been very promising applications of AI in the field of medicine, including medical imaging, in vitro diagnosis, intelligent rehabilitation, and prognosis. Breast cancer is one of the common malignant tumors in women and seriously threatens women’s physical and mental health. Early screening for breast cancer via mammography, ultrasound and magnetic resonance imaging (MRI) can significantly improve the prognosis of patients. AI has shown excellent performance in image recognition tasks and has been widely studied in breast cancer screening. This paper introduces the background of AI and its application in breast medical imaging (mammography, ultrasound and MRI), such as in the identification, segmentation and classification of lesions; breast density assessment; and breast cancer risk assessment. In addition, we also discuss the challenges and future perspectives of the application of AI in medical imaging of the breast.

Purpose: This study hypothesized that insurance denial would lead to bias and loss of statistical power when evaluating the results from an intent-to-treat (ITT), per-protocol, and as-treated analyses using a simulated randomized clinical trial comparing proton therapy to intensity modulated radiation therapy where patients incurred increasing rates of insurance denial. Methods and Materials: Simulations used a binary endpoint to assess differences between treatment arms after applying ITT, per-protocol, and as-treated analyses. Two scenarios were developed: 1 with clinical success independent of age and another assuming dependence on age. Insurance denial was assumed possible for patients

Breast cancer is one of the most commonly diagnosed malignancies. Although endocrine therapy improves the survival of patients with hormone receptor (HR)-positive breast cancer, the post-endocrine therapy strategy for metastatic breast cancer remains challenging. Herein, we report two patients who benefited from antiestrogen agents combined with an immunotherapy regimen to support the notion that an immunotherapy combination regimen may be a potential treatment for patients with HR-positive metastatic breast cancer post-endocrine therapy. Case 1 involved a patient with relapsed breast cancer with ovarian and brain metastases after endocrine therapy. After undergoing surgery for the ovarian lesions, she received three cycles of chemotherapy. Given that the lesions in the brain did not change, chemotherapy was discontinued. A high T cell receptor (TCR) repertoire (high Shannon index and clonality) was observed in the tumor. Considering the patient's preference and safety, and the efficacy of immunotherapy, she was administered with letrozole combined with pembrolizumab. The patient achieved a partial response, and the progression-free survival (PFS) was more than 21 months. Case 2 involved a patient with breast cancer with multiple bone metastases. After failure of combined radiotherapy and chemotherapy, the patient received tamoxifen combined with pembrolizumab based on the patient's preference and clinical biomarkers of a positive differentiation cluster of eight tumor-infiltrating lymphocytes and a high TCR repertoire (high Shannon index and clonality) in the tumor. The patient's bone pain and biomarkers were relieved after the treatment. The patients completed six cycles of pembrolizumab, and the PFS was more than 21 months. In conclusion, our study confirmed that antiestrogen agents combined with an immunotherapy regimen is a promising treatment for patients with HR-positive metastatic breast cancer.

Early and profound pathological changes are evident in the locus coeruleus (LC) in dementia and Parkinson's disease, with effects on arousal, attention, cognitive and motor control. The LC can be identified in vivo using non-invasive magnetic resonance imaging techniques which have potential as biomarkers for detecting and monitoring disease progression. Technical limitations of existing imaging protocols have impaired the sensitivity to regional contrast variance or the spatial variability on the rostrocaudal extent of the LC, with spatial mapping consistent with post mortem findings. The current study employs a sensitive magnetisation transfer sequence using ultrahigh field 7T MRI to investigate the LC structure in vivo at high-resolution (0.4 × 0.4 × 0.5 mm). Magnetisation transfer images from 53 healthy older volunteers (52 - 84 years) clearly revealed the spatial features of the LC and were used to create a probabilistic LC atlas for older adults. This atlas may be especially relevant for studying disorders associated with older age. To use the atlas does not require use of the same MT sequence of 7T MRI, provided good co-registration and normalisation is achieved. Consistent rostrocaudal gradients of slice-wise volume, contrast and variance along the LC were observed, mirroring distinctive ex vivo spatial distributions of LC cells in its subregions. The contrast-to-noise ratios were calculated for the peak voxels, and for the averaged signals within the atlas, to accommodate the volumetric differences in estimated contrast. The probabilistic atlas is freely available, and the MRI dataset will be made available for non-commercial research, for replication or to facilitate accurate LC localisation and unbiased contrast extraction in future studies.

The smart grid with flexible topologies receives intensive attention recently. Transmission switching (TS) alters the power system topology during operation, and has been demonstrated for the advantage of economic and secure operation of power systems. TS includes a chain of sequential switching actions which bring disturbances to the system if the switching actions are not properly designed. Unfortunately, it is not considered or well-studied in existing works. In this paper, a new multi-period TS model that considers the transition security and a two-stage iterative method are proposed. In the TS model, we take into account the fact that only one line is permitted to switch up or down at a time and the security of each switching action is considered. The proposed iterative solution makes the TS model more tractable under AC framework. Case studies on a 6-bus system and the IEEE 57-bus test system have varified the effectiveness of the proposed model. Numerical results show that: ➀ the consideration of transition security of TS is essential; ➁ the transition path is directly related to secure and fast the transmission switching; ➂ the proposed model and solution method give an effective way to determine the switching sequence and switching timing under transition security criteria.