[Cerebral oxygen metabolism and brain electrical activity of healthy full-term neonates in high-altitude areas: a multicenter clinical research protocol]. / é«˜æµ·æ‹”åœ°åŒºå¥åº·è¶³æœˆæ–°ç”Ÿå„¿è„‘æ°§ä»£è°¢åŠè„‘ç”µæ´»åŠ¨å·®å¼‚çš„å¤šä¸­å¿ƒä¸´åºŠç ”ç©¶æ–¹æ¡ˆ.

Further evidence is needed to explore the impact of high-altitude environments on the neurologic function of neonates. Non-invasive techniques such as cerebral near-infrared spectroscopy and amplitude-integrated electroencephalography can provide data on cerebral oxygenation and brain electrical activity. This study will conduct multiple cerebral near-infrared spectroscopy and amplitude-integrated electroencephalography monitoring sessions at various time points within the first 3 days postpartum for healthy full-term neonates at different altitudes. The obtained data on cerebral oxygenation and brain electrical activity will be compared between different altitudes, and corresponding reference ranges will be established. The study involves 6 participating centers in the Chinese High Altitude Neonatal Medicine Alliance, with altitude gradients divided into 4 categories: 800 m, 1 900 m, 2 400 m, and 3 500 m, with an anticipated sample size of 170 neonates per altitude gradient. This multicenter prospective cohort study aims to provide evidence supporting the impact of high-altitude environments on early brain function and metabolism in neonates.

CRISPR-Cas12a-activated palindrome-catalytic hairpin assembly for ultrasensitive fluorescence detection of HIV-1 DNA.

Accurate analysis of HIV DNA is valuable for the diagnosis of AIDS. Herein, an ultrasensitive and specific fluorescence method was developed for HIV-1 DNA detection based on CRISPR-Cas12a-activated palindrome-catalytic hairpin assembly (CRISPR-Cas12a-PCHA). The presence of HIV-1 DNA activated the trans-cleavage activity of CRISPR-Cas12a, which could continuously digest the DNA fragment of hairpins connected to magnetic beads to expose single-stranded RNA. After magnetic separation, the exposed RNA triggered multiple PCHA reactions, generating many Y-shaped DNA structures that were self-assembled into the DNA superstructures via the hybridization of palindromic sticky ends, leading to the release of amounts of fluorescence signal. Different from the reported recently biosensing strategies of nucleic acid amplification technologies-activated CRISPR-Cas12a, CRISPR-Cas12a-PCHA endowed the strategy with unique advantages of simple sample pretreatment, direct duplex target detection, and ultrahigh sensitivity. The strategy was able to resist the interference of the complex matrix in real sample and distinguish between HIV patients and healthy persons. Thus, the method is a promising tool for ultrasensitive and specific detection of HIV-1 DNA for AIDS diagnosis.

Case report: novel mutations of NDUFS6 and NHLRC2 genes potentially cause the quick postnatal death of a Chinese Hani minority neonate with mitochondrial complex I deficiency and FINCA syndrome.

INTRODUCTION: Mitochondrial complex I deficiency (MCID) and abbFINCA syndrome are lethal congenital diseases and cases in the neonatal period are rarely reported. Here, we identified a Chinese Hani minority neonate with rare MCID and FINCA syndrome. This study was to analyze the clinical manifestations and pathogenic gene variations, and to investigate causes of quick postnatal death of patient and possible molecular pathogenic mechanisms. PATIENT CONCERNS: A 17-day-old patient had reduced muscle tension, diminished primitive reflexes, significantly abnormal blood gas analysis, and progressively increased blood lactate and blood glucose. Imaging studies revealed pneumonia, pulmonary hypertension, and brain abnormalities. DIAGNOSIS: Whole-exome sequencing revealed that the NDUFS6 gene of the patient carried c. 344G > T (p.C115F) novel homozygous variation, and the NHLRC2 gene carried c. 1749C > G (p.F583L) and c. 2129C > T (p.T710M) novel compound heterozygous variation. INTERVENTIONS AND OUTCOMES: The patient was given endotracheal intubation, respiratory support, high-frequency ventilation, antishock therapy, as well as iNO and Alprostadil to reduce pulmonary hypertension and maintain homeostatic equilibrium. However, the patient was critically ill and died in 27 days. CONCLUSION: The patient has MCID due to a novel mutation in NDUFS6 and FINCA syndrome due to novel mutations in NHLRC2, which is the main reason for the rapid onset and quick death of the patient.

Corrigendum: Deep Learning-Enabled Clinically Applicable CT Planbox for Stroke With High Accuracy and Repeatability.

[This corrects the article DOI: 10.3389/fneur.2022.755492.].

Deep Learning-Enabled Clinically Applicable CT Planbox for Stroke With High Accuracy and Repeatability.

Background: Computed tomography (CT) plays an essential role in classifying stroke, quantifying penumbra size and supporting stroke-relevant radiomics studies. However, it is difficult to acquire standard, accurate and repeatable images during follow-up. Therefore, we invented an intelligent CT to evaluate stroke during the entire follow-up. Methods: We deployed a region proposal network (RPN) and V-Net to endow traditional CT with intelligence. Specifically, facial detection was accomplished by identifying adjacent jaw positions through training and testing an RPN on 76,382 human faces using a preinstalled 2-dimensional camera; two regions of interest (ROIs) were segmented by V-Net on another training set with 295 subjects, and the moving distance of scanning couch was calculated based on a pre-generated calibration table. Multiple cohorts including 1,124 patients were used for performance validation under three clinical scenarios. Results: Cranial Automatic Planbox Imaging Towards AmeLiorating neuroscience (CAPITAL)-CT was invented. RPN model had an error distance of 4.46 ± 0.02 pixels with a success rate of 98.7% in the training set and 100% with 2.23 ± 0.10 pixels in the testing set. V-Net-derived segmentation maintained a clinically tolerable distance error, within 3 mm on average, and all lines presented with a tolerable angle error, within 3° on average in all boundaries. Real-time, accurate, and repeatable automatic scanning was accomplished with and a lower radiation exposure dose (all P < 0.001). Conclusions: CAPITAL-CT generated standard and reproducible images that could simplify the work of radiologists, which would be of great help in the follow-up of stroke patients and in multifield research in neuroscience.

Evaluation of the clinical effect of an artificial intelligence-assisted diagnosis and treatment system for neonatal seizures in the real world: a multicenter clinical study protocol. / æ–°ç”Ÿå„¿æƒŠåŽ¥æ™ºèƒ½è¯Šç–—ç³»ç»ŸçœŸå®žåœºæ™¯ä¸´åºŠå®žæ–½æ•ˆæžœç»¼åˆè¯„ä»·çš„å¤šä¸­å¿ƒä¸´åºŠç ”ç©¶æ–¹æ¡ˆ.

Neonatal seizures are the most common clinical manifestations of critically ill neonates and often suggest serious diseases and complicated etiologies. The precise diagnosis of this disease can optimize the use of anti-seizure medication, reduce hospital costs, and improve the long-term neurodevelopmental outcomes. Currently, a few artificial intelligence-assisted diagnosis and treatment systems have been developed for neonatal seizures, but there is still a lack of high-level evidence for the diagnosis and treatment value in the real world. Based on an artificial intelligence-assisted diagnosis and treatment systems that has been developed for neonatal seizures, this study plans to recruit 370 neonates at a high risk of seizures from 6 neonatal intensive care units (NICUs) in China, in order to evaluate the effect of the system on the diagnosis, treatment, and prognosis of neonatal seizures in neonates with different gestational ages in the NICU. In this study, a diagnostic study protocol is used to evaluate the diagnostic value of the system, and a randomized parallel-controlled trial is designed to evaluate the effect of the system on the treatment and prognosis of neonates at a high risk of seizures. This multicenter prospective study will provide high-level evidence for the clinical application of artificial intelligence-assisted diagnosis and treatment systems for neonatal seizures in the real world.

Ultrasensitive electrochemical detection of hepatitis C virus core antigen using terminal deoxynucleotidyl transferase amplification coupled with DNA nanowires.

Early diagnosis of hepatitis C virus (HCV) infection is essential to prevent disease from spreading and progression. Herein, a novel electrochemical biosensor was developed for ultrasensitive detection of HCV core antigen (HCVcAg) based on terminal deoxynucleotidyl transferase (TdT) amplification and DNA nanowires (DNW). After sandwich-type antibody-antigen recognition, the antibody-conjugated DNA was pulled to the electrode surface and further extended into a long DNA sequence by robust TdT reaction. Then, large numbers of methylene blue-loaded DNW (MB@DNW) as signal labels are linked to the extended DNA sequence. This results in an amplified electrochemical signal for HCVcAg determination, typically measured at around -0.25 V (Ag/AgCl). Under the optimum conditions, the proposed biosensor achieved a wide linear range for HCVcAg from 0.1 to 312.5 pg/mL with a low limit of detection of 32 fg/mL. The good practicality of the biosensor was demonstrated by recovery experiment (recoveries from 98 to 104% with RSD of 2.5-4.4%) and comparison with enzyme-linked immunosorbent assay (ELISA). Given the highlighted performance, the biosensor is expected to act as a reliable sensing tool for HCVcAg determination in clinics. Schematic representation of the ultrasensitive electrochemical biosensor based on terminal deoxynucleotidyl transferase (TdT) amplification linked with methylene blue-loaded DNA nanowires (MB@DNW), which can be applied to the determination of hepatitis C virus core antigen (HCVcAg) in clinical samples. dTTPs, 2'-deoxythymidine 5'-triphosphate.

Ecological and Human Health Risks of Heavy Metals in Shooting Range Soils: A Meta Assessment from China.

Contamination of shooting ranges by heavy metals in particular Pb represents a widespread environmental issue attracting concern worldwide. Contaminant accumulation in shooting range soils can pose potential ecological risks and health risks for shooters and workers. Based on the published data on metal contamination at five shooting ranges in China, potential ecological and human health risks of several metals, and in particular, Pb were assessed for the five surveyed shooting ranges. Data show the mean concentrations of Pb, Cu, Hg, Sb, Ni and Cr in various ranges were all higher than the local soil background values, implying their accumulation was induced by shooting activities. The degree of contamination varied with sites and metals, very high Pb contamination at Range 1, Range 2 and Range 5-1, while moderate Pb contamination at Range 3 and Range 5-2. Comparatively, As, Zn and Co showed no contamination. Among the surveyed metals, Pb, Cu, Hg and Sb in shooting range soils displayed relatively high potential ecological risks. The overall degree of potential ecological risk was very high at Range 1 and Range 2, considerable at Range 4 and Range 5-1, and low at Range 3 and Range 5-2. The mean HI (hazard index) of Pb at Range 2 and the maximum HI values at Range 1 and Range 4 were higher than 1, suggesting a possibility of non-carcinogenic risks of Pb contamination at these sites. However, Pb in other range soils and other metals, across the five ranges, all exhibited no non-carcinogenic risks. The cancer risks of the four carcinogenic contaminants (As, Co, Cr, and Ni) were acceptable or negligible at all ranges. In conclusion, contamination of Pb and other metals such as Cu, Hg and Sb can cause various potential ecological risks at all the surveyed ranges, but only Pb at three ranges shows possible health risks. Contamination of Pb in the surveyed shooting ranges should be managed to reduce its possible environmental and health risks.

[Association between interleukin-8 rs4073 polymorphisms and susceptibility to neonatal sepsis].

OBJECTIVE: To study the association between interleukin-8 (IL-8) rs4073 polymorphisms and susceptibility to sepsis in full-term neonates through a prospective study. METHODS: A total of 50 neonates who were diagnosed with sepsis based on positive blood culture from January to December 2017 were enrolled as the sepsis group. Fifty neonates who had clinical symptoms and negative blood culture were enrolled as the clinical sepsis group. Fifty neonates without infection were enrolled as the control group. Sequencing was used to detect the polymorphisms of IL-8 rs4073. The three groups were compared in terms of the frequencies of genotypes and alleles. A multivariate logistic regression analysis was used to investigate the association of IL-8 rs4073 genotypes with sepsis in full-term neonates. RESULTS: There were significant differences in the frequencies of genotypes and alleles at IL-8 rs4073 among the three groups (P<0.05). The logistic regression analysis showed that a low gestational age and TT genotype at IL-8 rs4073 were risk factors for the pathogenesis of sepsis in neonates (P<0.05). CONCLUSIONS: The full-term neonates with TT genotype at IL-8 rs4073 may be susceptible to sepsis.

Precise pulmonary scanning and reducing medical radiation exposure by developing a clinically applicable intelligent CT system: Toward improving patient care.

BACKGROUND: Interstitial lung disease requires frequent re-examination, which directly causes excessive cumulative radiation exposure. To date, AI has not been applied to CT for enhancing clinical care; thus, we hypothesize AI may empower CT with intelligence to realize automatic and accurate pulmonary scanning, thus dramatically decrease medical radiation exposure without compromising patient care. METHODS: Facial boundary detection was realized by recognizing adjacent jaw position through training and testing a region proposal network (RPN) on 76,882 human faces using a preinstalled 2-dimensional camera; the lung-fields was then segmented by V-Net on another training set with 314 subjects and calculated the moving distance of the scanning couch based on a pre-generated calibration table. A multi-cohort study, including 1,186 patients was used for validation and radiation dose quantification under three clinical scenarios. FINDINGS: A U-HAPPY (United imaging Human Automatic Planbox for PulmonarY) scanning CT was designed. Error distance of RPN was 4·46±0·02 pixels with a success rate of 98·7% in training set and 2·23±0·10 pixels with 100% success rate in testing set. Average Dice's coefficient was 0·99 in training set and 0·96 in testing set. A calibration table with 1,344,000 matches was generated to support the linkage between camera and scanner. This real-time automation makes an accurate plan-box to cover exact location and area needed to scan, thus reducing amounts of radiation exposures significantly (all, P<0·001). INTERPRETATION: U-HAPPY CT designed for pulmonary imaging acquisition standardization is promising for reducing patient risk and optimizing public health expenditures. FUNDING: The National Natural Science Foundation of China.

Involvement of human and canine MRP1 and MRP4 in benzylpenicillin transport.

The blood-brain barrier (BBB) is a dynamic and complex interface between blood and the central nervous system (CNS). It protects the brain by preventing toxic substances from entering the brain but also limits the entry of therapeutic agents. ATP-binding cassette (ABC) efflux transporters are critical for the functional barrier and present a formidable impediment to brain delivery of therapeutic agents including antibiotics. The aim of this study was to investigate the possible involvement of multidrug resistance-associated protein 1 and 4 (MRP1 and MRP4), two ABC transporters, in benzylpenicillin efflux transport using wild-type (WT) MDCKII cells and cells overexpressing those human transporters, as well as non-selective and selective inhibitors. We found that inhibiting MRP1 or MRP4 significantly increased [3H]benzylpenicillin uptake in MDCKII-WT, -MRP1 or -MRP4 cells. Similar results were also found in HepG2 cells, which highly express MRP1 and MRP4, and hCMEC/D3 cells which express MRP1. The results indicate that human and canine MRP1 and MRP4 are involved in benzylpenicillin efflux transport. They could be potential therapeutic targets for improving the efficacy of benzylpenicillin for treating CNS infections since both MRP1 and MRP4 express at human blood-brain barrier.

Role of Human Breast Cancer Related Protein versus P-Glycoprotein as an Efflux Transporter for Benzylpenicillin: Potential Importance at the Blood-Brain Barrier.

While the blood-brain barrier (BBB) protects the brain by controlling the access of solutes and toxic substances to brain, it also limits drug entry to treat central nervous system disorders. Many drugs are substrates for ATP-binding cassette (ABC) transporters at the BBB that limit their entry into the brain. The role of those transporters in limiting the entry of the widely prescribed therapeutic, benzylpenicillin, has produced conflicting results. This study investigated the possible potential involvement of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP), two ABC transporters, in benzylpenicillin transport at BBB in human using MDCKII cells overexpressing those transporters as well as pharmacological inhibition. MDCKII cells overexpressing human BCRP (MDCKII-BCRP) but not those overexpressing human P-gp (MDCKII-MDR cells) had reduced [3H]benzylpenicillin uptake. Similarly, inhibiting BCRP increased [3H]benzylpenicillin uptake in MDCKII-BCRP cells, while inhibiting P-gp in MDCKII-MDR cells had no effect on uptake although there was evidence that benzylpenicillin is a substrate for canine P-gp. While inhibiting BCRP affected [3H]benzylpenicillin cell concentrations it did not affect transepithelial flux in MDCKII-BCRP cells. In summary, the results indicate that human BCRP and not human P-gp is involved in benzylpenicillin transport. However, targeting BCRP alone was not sufficient to alter transepithelial flux in MDCKII cells. Whether it would be sufficient to alter blood-to-brain flux at the human BBB remains to be investigated.