Artificial intelligence in cancer pathology: Challenge to meet increasing demands of precision medicine.

Clinical efforts on precision medicine are driving the need for accurate diagnostic, new prognostic and novel drug predictive assays to inform patient selection and stratification for disease treatment. Accumulating evidence suggests that a combination of cancer pathology and artificial intelligence (AI) can meet this requirement. In the present review, the past, present and emerging integrations of AI into cancer pathology were comprehensively reviewed, which were divided into four main groups to highlight the roles of AI­integrated cancer pathology in precision medicine. Furthermore, the unsolved problems and future challenges in AI­integrated cancer pathology were also discussed. It was found that, although AI­integrated cancer pathology could enable the amalgamation of complex morphological phenotypes with the multi­omics datasets that drove precision medicine, synergies of cancer pathology with other medical tools could be more promising for the clinic when making an accurate and rapid decision in personalized treatments for patients. It was hypothesized by the authors that exploring the potential advantages of the multimodal integration of cancer pathology, imaging­omics, protein­omics and other­omics, as well as clinical data to decide upon appropriate management and improve patient outcomes may be the most challenging issue of cancer precision medicine in the future.

[Professor ZHANG Wei-hua's clinical experience in chronic somatic pain treated with zhidong needling techniques].

The paper summarizes professor ZHANG Wei-hua's clinical experience for the treatment of chronic somatic pain with zhidong needling techniques. In terms of the characteristics of chronic somatic pain, professor ZHANG has integrated zhidong needling with acupuncture kinetic therapy. The satisfactory therapeutic effects are obtained by selecting the painful points and regions as the treatment sites and the specific techniques of zhidong needling depending on the size of affected area, the depth of illness, the size and shape of the cord-like muscle, etc. Five techniques of zhidong needling are used accordingly with twirling, pulling, lifting and thrusting, surrounding needling methods involved, as well as with the manipulation speed, direction and frequency considered.

Miniaturized CO2 Gas Sensor Using 20% ScAlN-Based Pyroelectric Detector.

NDIR CO2 gas sensors using a 10-cm-long gas channel and CMOS-compatible 12% doped ScAlN pyroelectric detector have previously demonstrated detection limits down to 25 ppm and fast response time of ∼2 s. Here, we increase the doping concentration of Sc to 20% in our ScAlN-based pyroelectric detector and miniaturize the gas channel by ∼65× volume with length reduction from 10 to 4 cm and diameter reduction from 5 to 1 mm. The CMOS-compatible 20% ScAlN-based pyroelectric detectors are fabricated over 8-in. wafers, allowing cost reduction leveraging on semiconductor manufacturing. Cross-sectional TEM images show the presence of abnormally oriented grains in the 20% ScAlN sensing layer in the pyroelectric detector stack. Optically, the absorption spectrum of the pyroelectric detector stack across the mid-infrared wavelength region shows ∼50% absorption at the CO2 absorption wavelength of 4.26 µm. The pyroelectric coefficient of these 20% ScAlN with abnormally oriented grains shows, in general, a higher value compared to that for 12% ScAlN. While keeping the temperature variation constant at 2 °C, we note that the pyroelectric coefficient seems to increase with background temperature. CO2 gas responses are measured for 20% ScAlN-based pyroelectric detectors in both 10-cm-long and 4-cm-long gas channels, respectively. The results show that for the miniaturized CO2 gas sensor, we are able to measure the gas response from 5000 ppm down to 100 ppm of CO2 gas concentration with CO2 gas response time of ∼5 s, sufficient for practical applications as the average outdoor CO2 level is ∼400 ppm. The selectivity of this miniaturized CO2 gas sensor is also tested by mixing CO2 with nitrogen and 49% sulfur hexafluoride, respectively. The results show high selectivity to CO2 with nitrogen and 49% sulfur hexafluoride each causing a minimum ∼0.39% and ∼0.36% signal voltage change, respectively. These results bring promise to compact and miniature low cost CO2 gas sensors based on pyroelectric detectors, which could possibly be integrated with consumer electronics for real-time air quality monitoring.

Comparison of outcomes between Zero-p implant and anterior cervical plate interbody fusion systems for anterior cervical decompression and fusion: a systematic review and meta-analysis of randomized controlled trials.

PURPOSE: The clinical outcomes of using a zero-profile for anterior cervical decompression and fusion were evaluated by comparison with anterior cervical plates. METHODS: All of the comparative studies published in the PubMed, Cochrane Library, Medline, Web of Science, EBSOChost, and EMBASE databases as of 1 October 2021 were included. All outcomes were analysed using Review Manager 5.4. RESULTS: Seven randomized controlled studies were included with a total of 528 patients, and all studies were randomized controlled studies. The meta-analysis outcomes indicated that the use of zero-profile fixation for anterior cervical decompression and fusion was better than anterior cervical plate fixation regarding the incidence of postoperative dysphagia (P < 0.05), adjacent-level ossification (P < 0.05), and operational time (P < 0.05). However, there were no statistically significant differences in intraoperative blood loss, Visual Analogue Scale, Neck Disability Index, or Japanese Orthopaedic Association scale (all P > 0.05) between the zero-profile and anterior cervical plate groups. CONCLUSIONS: The systematic review and meta-analysis indicated that zero-profile and anterior cervical plates could result in good postoperative outcomes in anterior cervical decompression and fusion. No significant differences were found in intraoperative blood loss, Visual Analogue Scale, Neck Disability Index, or Japanese Orthopaedic Association scale. However, the zero-profile is superior to the anterior cervical plate in the following measures: incidence of postoperative dysphagia, adjacent-level ossification, and operational time. PROSPERO registration CRD42021278214.

Target-swiped DNA lock for electrochemical sensing of miRNAs based on DNAzyme-assisted primer-generation amplification.

As an extremely important post-transcriptional regulator, miRNAs are involved in a variety of crucial biological processes, and the abnormal expressions of miRNAs are closely related to a variety of diseases. In this work, for the first time, we designed a nucleic acid lock nanostructure for specific detection of miRNA-21, which changes the self-structure to "active conformation" by binding the target, in order to generate triggers to initiate the subsequent reaction. Emphatically, this flexible nucleic acid lock is capable of self-cleaving without the assistance of external component, overcoming the disadvantages of the complex design and requiring protease assistance in traditional nanostructure. Moreover, the combination of DNAzyme and RCA technology not only greatly improves the efficiency of signal amplification but also enables primer generation to simultaneous cascade RCA amplification. Additionally, the electrochemical detection technology based on silver nanoclusters overcomes the shortcomings of traditional detection methods such as low sensitivity and complex operation. The detection limit achieved was 9.3 aM with a wide dynamic response ranging from 10 aM to 100 pM (at the DPV peak of - 0.5 V), which is comparable to most of the reported studies. Therefore, our work provided an ultra-sensitive way for the detection of miRNAs using nanostructures and revealed an effective means for disease theranostics and cancer diagnosis. In this work, for the first time, we designed a nucleic acid lock nanostructure based on its self-structural transformation for the specific detection of miRNA. And the combination of DNAzyme and cascade RCA reaction greatly improved the signal amplification efficiency.

Significantly boosted oxygen electrocatalysis with cooperation between cobalt and iron porphyrins.

Developing electrocatalysts for the oxygen reduction reaction (ORR) and the oxygen evolution reaction (OER) is of great importance. Herein, Co tetrakis(pentafluorophenyl)porphyrin (Co-P) and Fe chloride tetrakis(pentafluorophenyl)porphyrin (Fe-P) were loaded on carbon nanotubes (CNTs) for combining the electrocatalytic advantages of both Co-P and Fe-P. The resultant (Co-P)0.5(Fe-P)0.5@CNT composite displayed significantly boosted activity for the selective four-electron ORR with a half-wave potential of 0.80 V versus reversible hydrogen electrode (RHE) and for the OER with a potential of 1.65 V versus RHE to obtain 10 mA cm-2 current density in 0.1 M KOH. A Zn-air battery assembled from (Co-P)0.5(Fe-P)0.5@CNT exhibited a small charge-discharge voltage gap of 0.74 V at 2 mA cm-2, a high power density of 174.5 mW cm-2 and a good rechargeable stability (>120 cycles).

In-situ monitoring of phenol in surface waters by diffusive gradients in thin films technique based on the nanocomposites of zero-valent iron@biochar.

The nano-sized zero valent iron assisted biochar from hazelnut shell (nZVI@biochar) was prepared and assessed for the feasibility as the binding agent in diffusive gradients in thin-films (DGT) technique. The 1.5% agarose solution containing the optimal nZVI@biochar dose of 15 g L-1 was used to prepare the nZVI@biochar binding gel which owned a high capacity (1010 ± 50 µg disc-1) and a rapid uptake within 30 min. The elution efficiency of phenol from the loaded binding gel was up to 99.3% using the mixture of 1% hydroxylamine hydrochloride and 0.05 mol L-1 HCl. The phenol uptake of nZVI@biochar-DGT increased linearly with the increase of deployment time (R2 = 0.9938) and was in accord with the theoretical values from DGT equation, while there was no notable interference of the sample matrixes on the phenol uptake of nZVI@biochar-DGT in the spiked freshwaters. The good performance of nZVI@biochar-DGT was found under a range of pH (4.1-10.2), ionic strength (as pNaNO3) (0.155-4), and dissolved organic matter up to 20 mg L-1. In field, the monitoring of nZVI@biochar-DGT was more representative than the results from the grab-sampling with better precision and lower sampling frequency, which can provide reliable information, reduce the cost of human resources, and improve efficiency. These illustrate that the nZVI@biochar is more suitable as the binding agent of DGT for uptake of phenol and nZVI@biochar-DGT is an effective tool to monitor in-situ phenol in waters.

Relationship between histogram metrics of pharmacokinetic parameters of DCE-MRI and histological phenotype in breast cancer.

BACKGROUND: To investigate the correlation between quantitative pharmacokinetic parameters and clinicopathological prognostic biomarkers including estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and MiB1 (Ki-67) in patients with breast cancer, the image histogram analysis was performed on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). METHODS: The reference region model (RRM) was used to calculate the quantitative permeability parameters, including reference region volume transfer constant (Ktrans,RR ), the rate constant of tissue of interest (Kep,TOI ), and the rate constant of reference region (Kep,RR ). Histogram analysis was performed to compare these parameters between ER/PR/HER2/Ki-67 positive and negative groups. The performance of the histogram parameters Ktrans,RR , Kep,TOI and Kep,RR in differential diagnosis of immunohistochemistry results was conducted by receiver operating characteristic (ROC) curve analysis. RESULTS: All the histogram metrics of Kep,TOI significantly differed between ER/PR positive and negative groups (P<0.05). However, Ktrans,RR and Kep,RR did not significantly differ between ER/PR positive and negative groups (P>0.05). The 10th percentile, energy, entropy and variance of Ktrans,RR , and almost all the histogram parameters of Kep,TOI except for variance significantly differed between HER2 positive and negative groups (all P<0.05). The energy of Ktrans,RR significantly differed between Ki-67 positive and negative groups (P<0.05). The skewness and energy of Kep,TOI showed the highest AUC of 0.977 and 0.879 in differentiating ER/PR status. The energy of Ktrans,RR presented the highest AUC in the differentiation of HER2 and Ki-67. CONCLUSIONS: Histogram analysis on quantitative pharmacokinetic breast parameters using DCE-MRI improves the performance in differentiation of histological phenotypes of breast cancer.

Ureter tissue engineering with vessel extracellular matrix and differentiated urine-derived stem cells.

OBJECTIVE: To assess the possibility of ureter tissue engineering using vessel extracellular matrix (VECM) and differentiated urine-derived stem cells (USCs) in a rabbit model. METHODS: VECM was prepared by a modified technique. USCs were isolated from human urine samples and cultured with an induction medium for the differentiation of the cells into urothelium and smooth muscle phenotypes. For contractile phenotype conversion, the induced smooth muscle cells were transfected with the miR-199a-5p plasmid. The differentiated cells were seeded onto VECM and cultured under dynamic conditions in vitro for 2 weeks. The graft was tubularized and wrapped by two layers of the omentum of a rabbit for vascularization. Then, the maturated graft was used for ureter reconstruction in vivo. RESULTS: VECM has microporous structures that allow cell infiltration and exhibit adequate biocompatibility with seeding cells. USCs were isolated and identified by flow cytometry. After induction, the urothelium phenotype gene was confirmed at mRNA and protein levels. With the combined induction by TGF-ß1 and miR-199a-5p, the differentiated cells can express the smooth muscle phenotype gene and convert to the contractile phenotype. After seeding cells onto VECM, the induced urothelium cells formed a single epithelial layer, and the induced smooth muscle cells formed a few cell layers during dynamic culture. After 3 weeks of omental maturation, tubular graft was vascularized. At 2 months post ureter reconstruction, histological evaluation showed a clearly layered structure of ureter with multilayered urothelium over the organized smooth muscle tissue. CONCLUSION: By seeding differentiated USCs onto VECM, a tissue-engineered graft could form multilayered urothelium and organized smooth muscle tissue after ureteral reconstruction in vivo. STATEMENT OF SIGNIFICANCE: Cell-based tissue engineering offers an alternative technique for urinary tract reconstruction. In this work, we describe a novel strategy for ureter tissue engineering. We modified the techniques of vessel extracellular matrix (VECM) preparation and used a dynamic culture system for seeding cells onto VECM. We found that VECM had the trait of containing VEGF and exhibited blood vessel formation potential. Urine-derived stem cells (USCs) could be differentiated into urothelial cells and functional contractile phenotype smooth muscle cells in vitro. By seeding differentiated USCs onto VECM, a tissue-engineered graft could form multilayered urothelium and organized smooth muscle tissue after ureteral reconstruction in vivo. This strategy might be applied in clinical research for the treatment of long-segment ureteral defect.

Role of magnetic resonance spectroscopy and susceptibility weighted imaging in cerebral alveolar echinococcosis.

BACKGROUND: To analyze the characteristic performance of magnetic resonance spectroscopy (MRS) and susceptibility weighted imaging (SWI) in cerebral alveolar echinococcosis (CAE). METHODS: We retrospectively analyzed 10 clinical-identified CAE cases MR performance, and summarized the MRS and SWI performance of CAE. RESULTS: The 10 cases of CAE all had the history of primary HAE, among who 6 cases had single lesion (60%), while the rest 4 cases had multiple lesions (40%); and 4 cases were concomitant with lung metastases. MRI performance: T2WI lesions were coal-like low-signal shadow, with multiple small vesicles inside the lesions; MRS performance: NAA, Cho and Cr significantly reduced, an abnormally high and steep crest was found at 1.4 ppm; the phase diagram and strength diagram of SWI showed isointensity. CONCLUSION: The MRS and SWI of CAE could provide important supplemental information for the diagnosis of CAE, especially the abnormally high and steep crest at 1.4 ppm provide the reliable image basis for the diagnosis and differential diagnosis of CAE.

Compact microelectrode array system: tool for in situ monitoring of drug effects on neurotransmitter release from neural cells.

This paper presents a compact microelectrode array (MEA) system, to study potassium ion-induced dopamine release from PC12 neural cells, without relying on a micromanipulator and a microscope. The MEA chip was integrated with a custom-made "test jig", which provides a robust electrical interfacing tool between the microchip and the macroenvironment, together with a potentiostat and a microfluidic syringe pump. This integrated system significantly simplifies the operation procedures, enhances sensing performance, and reduces fabrication costs. The achieved detection limit for dopamine is 3.8 x 10-2 muM (signal/noise, S/N = 3) and the dopamine linear calibration range is up to 7.39 +/- 0.06 muM (mean +/- SE). The effects of the extracelluar matrix collagen coating of the microelectrodes on dopamine sensing behaviors, as well as the influences of K+ and l-3,4-digydroxyphenylalanine concentrations and incubation times on dopamine release, were extensively studied. The results show that our system is well suited for biologists to study chemical release from living cells as well as drug effects on secreting cells. The current system also shows a potential for further improvements toward a multichip array system for drug screening applications.