Mesenchymal Stem Cell-Derived Exosomes Ameliorate Diabetic Kidney Disease Through the NLRP3 Signaling Pathway.

Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease worldwide. Exosomes (Exo) derived from human umbilical cord mesenchymal stem cells (HUC-MSCs) have been demonstrated to be an effective therapy for DKD, but the underlying mechanisms of this action remain poorly defined. We investigated the association of DKD with inflammasome activation and the pathophysiological relevance of Exo-mediated inflammation relief as well as damage repair in this progression. We co-cultured podocytes and HUC-MSCs derived Exo (MSCs-Exo) under high glucose (HG) and injected MSCs-Exo into diabetic mice, then we detected the NLRP3 inflammasome both in vitro and in vivo. We found that HG reduced the viability of podocytes, activated the NLRP3 signaling pathway and increased inflammation in podocytes and diabetic mice. MSCs-Exo attenuated the inflammation, including the expression of IL-6, IL-1ß, IL-18, TNF-α; depressed the activation of NLRP3 signaling pathway in podocytes under HG and diabetic mice, ameliorated kidney injury. Furthermore, miR-22-3p, which is relatively highly expressed miRNAs in exosomes of MSCs, may be the key point in this progress, by suppressing the expression of its known target, NLRP3. Knocking down miR-22-3p from MSCs-Exo abolished their anti-inflammation activity and beneficial function both in vitro and in vivo. Collectively, our results have demonstrated that exosomes transferring miR-22-3p protected the podocytes and diabetic mice from inflammation by mediating NLRP3 inflammasome, indicating that MSC-derived exosomes may be a promising therapeutic cell-free strategy for DKD.

Mesenchymal stem cell-derived exosomes ameliorate diabetic kidney disease through NOD2 signaling pathway.

BACKGROUND AND AIMS: Diabetic kidney disease (DKD) is one of the most common complications of diabetes. It is reported that mesenchymal stem cells (MSCs) derived exosomes (MSCs-Exo) may have great clinical application potential for the treatment of DKD, but the underlying mechanism has not been illustrated. To clarify the effect of MSC-Exo on NOD2 signaling pathway in podocytes under high glucose (HG) and DKD, we conduct this study. METHODS: We co-cultured podocytes and MSCs-Exo under 30 mM HG and injected MSCs-Exo into DKD mice, then we detected the NOD2 signaling pathway by western blot, qRT-PCT, immunofluorescence, transmission electron microscopy and immunohistochemistry both in vitro and in vivo. RESULTS: In vitro, HG lead to the apoptosis, increased the ROS level and activated the NOD2 signaling pathway in podocytes, while MSCs-Exo protected podocytes from injury reduced the expression of inflammatory factors including TNF-α, IL-6, IL-1ß, and IL-18 and alleviated the inflammatory response, inhibited the activation of NOD2 signaling pathway and the expression of it's downstream protein p-P65, p-RIP2, prevented apoptosis, increased cell viability in podocytes caused by HG. In vivo, MSCs-Exo alleviated renal injury in DKD mice, protected renal function, decreased urinary albumin excretion and inhibited the activation of NOD2 signaling pathway as well as the inflammation in renal tissue. CONCLUSION: MSCs-Exo protected the podocytes and DKD mice from inflammation by mediating NOD2 pathway, MSCs-Exo may provide a new target for the treatment of DKD.

Development and validation of a clinicoradiomic nomogram to assess the HER2 status of patients with invasive ductal carcinoma.

BACKGROUND: The determination of HER2 expression status contributes significantly to HER2-targeted therapy in breast carcinoma. However, an economical, efficient, and non-invasive assessment of HER2 is lacking. We aimed to develop a clinicoradiomic nomogram based on radiomics scores extracted from multiparametric MRI (mpMRI, including ADC-map, T2W1, DCE-T1WI) and clinical risk factors to assess HER2 status. METHODS: We retrospectively collected 214 patients with pathologically confirmed invasive ductal carcinoma between January 2018 to March 2021 from Fudan University Shanghai Cancer Center, and randomly divided this cohort into training set (n = 128, 42 HER2-positive and 86 HER2-negative cases) and validation set (n = 86, 28 HER2-positive and 58 HER2-negative cases) at a ratio of 6:4. The original and transformed pretherapy mpMRI images were treated by semi-automated segmentation and manual modification on the DeepWise scientific research platform v1.6 ( http://keyan.deepwise.com/ ), then radiomics feature extraction was implemented with PyRadiomics library. Recursive feature elimination (RFE) based on logistic regression (LR) and LASSO regression were adpoted to identify optimal features before modeling. LR, Linear Discriminant Analysis (LDA), support vector machine (SVM), random forest (RF), naive Bayesian (NB) and XGBoost (XGB) algorithms were used to construct the radiomics signatures. Independent clinical predictors were identified through univariate logistic analysis (age, tumor location, ki-67 index, histological grade, and lymph node metastasis). Then, the radiomics signature with the best diagnostic performance (Rad score) was further combined with significant clinical risk factors to develop a clinicoradiomic model (nomogram) using multivariate logistic regression. The discriminative power of the constructed models were evaluated by AUC, DeLong test, calibration curve, and decision curve analysis (DCA). RESULTS: 70 (32.71%) of the enrolled 214 cases were HER2-positive, while 144 (67.29%) were HER2-negative. Eleven best radiomics features were retained to develop 6 radiomcis classifiers in which RF classifier showed the highest AUC of 0.887 (95%CI: 0.827-0.947) in the training set and acheived the AUC of 0.840 (95%CI: 0.758-0.922) in the validation set. A nomogram that incorporated the Rad score with two selected clinical factors (Ki-67 index and histological grade) was constructed and yielded better discrimination compared with Rad score (p = 0.374, Delong test), with an AUC of 0.945 (95%CI: 0.904-0.987) in the training set and 0.868 (95%CI: 0.789-0.948; p = 0.123) in the validation set. Moreover, calibration with the p-value of 0.732 using Hosmer-Lemeshow test demonstrated good agreement, and the DCA verified the benefits of the nomogram. CONCLUSION: Post largescale validation, the clinicoradiomic nomogram may have the potential to be used as a non-invasive tool for determination of HER2 expression status in clinical HER2-targeted therapy prediction.

Characterization and Phylogenetic Analysis of the Mitochondrial Genome Sequence of Nisia fuliginosa (Hemiptera: Fulgoroidea: Meenoplidae).

We explored characterization of the mitochondrial genome (mitogenome or mtGenome) and phylogenetic analysis between 32 Fulgoroid species by sequencing and analyzing the mitogenome of Nisia fuliginosa Yang and Hu, 1985 (Hemiptera: Fulgoroidea: Meenoplidae), thereby making it the first determined mitogenome from the family Meenoplidae. The mitogenome was found to be 15,754 bp in length and contained 13 protein-coding genes (PCGs), 22 tRNA genes, two ribosomal RNA genes (rRNAs), and a control region. All PCGs started with typical ATN codons, except for nad1, which used GTG as the start codon. Canonical TAA termination codons were found in 10 PCGs and the remaining three genes (cox2, nad6, and nad1) had incomplete stop codons T. All tRNAs could fold into typical cloverleaf secondary structures, with the exception of trnC, trnV, and trnS1. Additionally, we compared the AT and GC skews of 13 PCGs of 32 Fulgoroidea mitogenomes, on the L-strand, the AT and GC skews were negative and positive, respectively. However, on the H-strand, the AT skew could be positive or negative and the GC skew was always negative. Phylogenetic results showed that the eight families of Fulgoroidea were divided into two large groups. Delphacidae formed a monophyletic group sister to a clade comprising Meenoplidae and other six families (Fulgoridae, Ricaniidae, Flatidae, Issidae, Caliscelidae, and Achilidae). Meenoplidae was located near the clade of Delphacidae, and Fulgoridae was located near the clade of Meenoplidae. Furthermore, Caliscelidae, Issidae, Ricaniidae, and Flatidae are closely related and they collectively formed a sister group to Achilidae.

Azopyrazole-Based Photoswitchable Anion Receptor for Dihydrogen Phosphate Transport.

Small-molecule anion carriers are potential reagents used in the treatment of diseases caused by dysregulated anion transport. Photoswitchable anion receptors, which can be reversibly switched between isomers by light and thereby cause reversible changes in anion binding affinity, have been receiving enormous interest. Here, based on the well-known photoswitch 1-N-methyl-3-phenylazopyrazole (3pzH), we designed a novel tetramethylamide-3pzH (3pzH_TA) photoswitchable receptor that achieves highly efficient and durable anion transportation. It enables high photoisomerization ratios of E → Z (>98%) and Z → E (97%) with a thermal half-life two times longer than that of 3pzH. We further demonstrated the high sensitivity of 3pzH_TA toward H2PO4- anion and revealed the key role of hydrogen bonds between H2PO4- and Z isomer in the strength of anion binding. Our findings open up a new strategy for the rational design and understanding of new types of photoswitchable anion receptors.

Evidences Suggesting that Distinct Immunological and Cellular Responses to Light Damage Distinguishes Juvenile and Adult Rat Retinas.

To unravel the mechanisms behind the higher resistance to light damage of juvenile (JR) versus adult (AR) rats, Sprague Dawley rats were exposed to a bright luminous environment of 10, 000 lux. The light-induced retinopathy (LIR) was assessed with histology, electroretinography and immunohistochemistry (IHC). In JR, 2 days of exposure induced the typical LIR, while >3 days added little LIR. IHC revealed a subtle migration of microglia (Iba1 marker) from the inner to the outer retina after 3 days of exposure in JR contrasting with the stronger reaction seen after 1 day in AR. Similarly, in JR, the Müller cells expressed less intense GFAP, CNTF and FGF2 staining compared to AR. Our results suggest that in JR the degree of retinal damage is not proportional to the duration of light exposure (i.e., dose-independent retinopathy), contrasting with the dose-dependent LIR reported in AR. The immature immune system in JR may explain the delayed and/or weaker inflammatory response compared to AR, a finding that would also point to the devastating contribution of the immune system in generating the LIR phenotype, a claim also advanced to explain the pathophysiology of other retinal degenerative disorders such as Age-related Macular Degeneration, Diabetic Retinopathy and Retinitis Pigmentosa.

ZnO nanorod/porous silicon nanowire hybrid structures as highly-sensitive NO2 gas sensors at room temperature.

ZnO nanorod/porous silicon nanowire (ZnO/PSiNW) hybrids with three different structures as highly sensitive NO2 gas sensors were obtained. PSiNWs were first synthesized by metal-assisted chemical etching, and then seeded in three different ways. After that ZnO nanorods were grown on the seeded surface of PSiNWs using a hydrothermal procedure. ZnO/PSiNW hybrids showed excellent gas sensing performance for various NO2 concentrations (5-50 ppm) at room temperature, and the electrical resistance change rate reached as high as 35.1% when responding to 50 ppm NO2. The distinct enhancement was mainly attributed to the faster carrier transportation after combination, the increase in gas sensing areas and the oxygen vacancy (VO) concentration. Moreover, the p-type gas sensing behavior was explained by the gas sensing mechanism and the effect of VO concentration on gas sensing properties was also discussed concerning the photoluminescence (PL) spectra performance.

Nitro-oleic acid attenuates OGD/R-triggered apoptosis in renal tubular cells via inhibition of Bax mitochondrial translocation in a PPAR-γ-dependent manner.

BACKGROUND: Nitroalkene derivatives of oleic acid (OA-NO2) serve as high-affinity ligand for PPAR-γ, which regulates apoptosis, oxidation and inflammation and plays a central role in ischemia-reperfusion injury. In the present study, we elucidated the protective mechanisms of OA-NO2 against renal ischemia-reperfusion injury. METHODS: HK-2 cells were subjected to oxygen and glucose deprivation followed by re-oxygenation (OGD/R) to mimic renal ischemia-reperfusion injury. Cell apoptosis was analyzed by flow cytometry. Bax mitochondrial translocation, cytochrome c and apoptosis-inducing factor (AIF) cytosolic leakage and Akt/Gsk 3ß phosphorylation were evaluated by Western blotting. Bax activation was visualized by immunocytochemistry. GW9662 and siRNA transfection were employed to examine the involvement of PPAR-γ. RESULTS: OGD/R injury promoted mitochondrial translocation and activation of Bax, leakage of cytochrome c and AIF, subsequent caspase-3 activation, and eventually cell apoptosis. Pre-incubation with OA-NO2 (1.25 µM, 45min) inhibited Bax activation and blocked apoptotic cascade, while the protective effects were negated by GW9662 or PPAR-γ siRNA. Moreover, OA-NO2 restored Akt and Gsk 3ß phosphorylation in a PPAR-γ-dependent way. CONCLUSION: These findings suggest that OA-NO2 attenuates OGD/R-induced apoptosis by inhibiting Bax translocation and activation and the subsequent mitochondria-dependent apoptotic cascade in a PPAR-γ dependent manner.

Enhanced field-emission of silver nanoparticle-graphene oxide decorated ZnO nanowire arrays.

This work presents a new method to improve the field emission (FE) properties of semiconductors decorated with low-cost graphene oxide (GO) nanosheets and trace amounts of noble metal. The Ag/GO/ZnO composite emitter exhibited efficient FE properties with a low turn-on field of 1.4 V µm(-1) and a high field enhancement factor of 7018. The excellent FE properties of the Ag/GO/ZnO composite can be attributed to the tunneling effect of electrons through the heterojunction. The FE properties of the Ag/GO/ZnO composite are slightly better than those of the Ag/ZnO composite which forms an energy well that collects electrons on interfaces when an electric field is applied. This behavior is associated with heterostructures that offer more contact points and protrusions between ZnO nanowire arrays (NWAs) and Ag/GO, which leads to easier electron transfer. High-resolution transmission electron microscopy (HRTEM) and X-ray photoelectron spectroscopy (XPS) were employed to characterise the connection and evolution of the ZnO NWAs and Ag/GO composites.

Stability of Hydrated Methylamine: Structural Characteristics and H2N···H-O Hydrogen Bonds.

Methylamine is the simplest aliphatic amine found in human urine, blood, and tissues. It is thought to play a significant part in central nervous system disturbances observed during renal and hepatic disease. In this work we have investigated the methylamine hydration clusters using a basin hopping (BH) algorithm with the density functional theory (DFT). The results presented herein yield a detailed understanding of the structure and stability for a system consisting of one methylamine molecule and up to seven waters: the most stable geometries arise from a fusion of tetramer or pentamer rings; by the geometrical parameters and topological parameters analysis, the strengths of the H2N···H-O hydrogen bonds of the global minima increase as the sizes of clusters increase, except for n = 5 where there is a slight fluctuation. This work may shed light on the form mechanism of methylamine existing in organisms and the hydration structures of larger molecules containing amino functional groups and their interaction with the water molecules nearby.

Properties and Atmospheric Implication of Methylamine-Sulfuric Acid-Water Clusters.

The presence of amines can increase aerosol formation rates. Most studies have been devoted to dimethylamine as the representative of amine; however, there have been a few works devoted to methylamine. In this study, theoretical calculations are performed on CH3NH2(H2SO4)m(H2O)n (m = 0-3, n = 0-3) clusters. In addition to the structures and energetics, we focused on determining the following characteristics: (1) the growth mechanism, (2) the hydrate distributions and the influences of humidity and temperature, (3) Rayleigh scattering properties. We explored the cluster growth mechanism from a thermodynamics aspect by calculating the Gibbs free energy of adding a water or sulfuric acid molecule step by step at three atmospherically relevant temperatures. The relative ease of the reaction at each step is discussed. From the analysis of hydrate distributions, we find that CH3NH2(H2SO4)(H2O)2, CH3NH2(H2SO4)2, and CH3NH2(H2SO4)3 are most likely to exist in the atmosphere. The general trend of hydration in all cases is more extensive with the growing relative humidity (RH), whereas the distributions do not significantly change with the temperature. Analysis of the Rayleigh scattering properties showed that both H2SO4 and H2O molecules could increase the Rayleigh scattering intensities and isotropic mean polarizabilities, with greater influence by the sulfuric acid molecules. This work sheds light on the mechanism for further research on new particle formation (NPF) containing methylamine in the atmosphere.

Two new species of the planthopper genus Metanigrus Tsaur, Yang & Wilson from China (Hemiptera: Fulgoromorpha: Meenoplidae), with an updated checklist and key to species.

Two new species of genus Metanigrus Tsaur, Yang & Wilson, 1986 (Fulgoromorpha, Meenoplidae), M. afflatus sp. nov. from Hainan Province and M. angularus sp. nov. from Yunnan Province, are described and illustrated, bringing the total number of species within the genus to 8. An updated checklist and identification key to known species of Metanigrus are provided.

Three new species of the planthopper genus Oecleopsis Emeljanov, 1971 from China (Hemiptera, Fulgoromorpha, Cixiidae).

Three new species of the genus Oecleopsis Emeljanov, 1971 from China, O.acerbus Lv & Chen, sp. nov. and O.panxianensis Lv & Chen, sp. nov. from Guizhou Province, and O.digitatus Lv & Chen, sp. nov. from Sichuan Province, are described and illustrated. With these additions, the number of species in the genus is increased to 18. An updated identification key and checklist of all known species of Oecleopsis are provided as well as a map of their geographic distributions.

Short-term effect of low-dose roxadustat combined with erythropoiesis-stimulating agent treatment for erythropoietin-resistant anemia in patients undergoing maintenance hemodialysis.

Background: Erythropoietin resistance is present in some patients with chronic kidney disease, especially in those undergoing hemodialysis, and is often treated using roxadustat rather than iron supplements and erythropoiesis-stimulating agents (ESAs). However, some patients cannot afford full doses of roxadustat. This retrospective study investigated the efficacy of low-dose roxadustat combined with recombinant human erythropoietin (rhuEPO) therapy in 39 patients with erythropoietin-resistant renal anemia undergoing maintenance hemodialysis (3-4 sessions/week). Methods: The ability of the combination of low-dose roxadustat and rhuEPO to increase the hemoglobin concentration over 12 weeks was assessed. Markers of iron metabolism were evaluated. Eligible adults received 50-60% of the recommended dose of roxadustat and higher doses of rhuEPO. Results: The mean hemoglobin level increased from 77.67 ± 11.18 g/dL to 92.0 ± 8.35 g/dL after treatment, and the hemoglobin response rate increased to 72%. The mean hematocrit level significantly increased from 24.26 ± 3.99% to 30.04 ± 3.69%. The soluble transferrin receptor level increased (27.29 ± 13.60 mg/L to 38.09 ± 12.78 mg/L), while the total iron binding capacity (49.22 ± 11.29 mg/L to 43.91 ± 12.88 mg/L) and ferritin level (171.05 ± 54.75 ng/mL to 140.83 ± 42.03 ng/mL) decreased. Conclusion: Therefore, in patients with ESA-resistant anemia who are undergoing hemodialysis, the combination of low-dose roxadustat and rhuEPO effectively improves renal anemia and iron metabolism.

Renal lymphatic ligation aggravates renal dysfunction through induction of tubular epithelial cell apoptosis in mononephrectomized rats.

AIMS: To further explore the mechanisms of apoptosis in mononephrectomized rats with renal lymph circulation disorder. METHODS: Animals were divided into three groups: rats with left renal lymph ligation and right nephrectomy (KL), rats with only right nephrectomy (KN) and sham-operated rats (sham). 24-h proteinuria and serum creatinine level were monitored. Indexes of oxidative stress were measured. Renal apoptosis was examined. Further biochemical analysis was provided using real-time PCR, western blot and Elisa techniques. RESULTS: Our results showed that renal lymphatic ligation induced renal tubular epithelial cell apoptosis and aggravated renal dysfunction in mononephrectomized rats. In addition, renal lymphatic ligation increased the activities of caspase-3, caspase-8 and caspase-9. Further investigation of mechanisms showed that renal lymphatic ligation up-regulated Fas expression, increased the ratio of Bax/Bcl-2, and also increased the levels of reactive oxygen species (ROS), malondialdehyde (MDA) while reducing superoxide dismutase (SOD) activity. CONCLUSION: These results indicated that disturbance of renal lymphatic circulation might lead to tubular epithelial cell apoptosis through activation of intrinsic and extrinsic apoptotic pathways, suggestive of an essential role of renal lymphatic circulation in the maintenance of tubular integrity and function.

Two new species of the planthopper genus Deferunda Distant from China (Hemiptera: Fulgoromorpha: Achilidae), with the first description of the male of Deferunda acuminata Chou & Wang.

Two new species of the genus Deferunda Distant, 1912, D. dentata sp. nov. and D. interanea sp. nov. from China (Shandong and Hainan provinces, respectively), are described and illustrated, bringing the total number of species within the genus to 17. The male genitalia of D. acuminata Chou & Wang, 1985 is described and illustrated for the first time. Geographical information, a checklist and key to all known species of Deferunda are provided.

FN1 and TGFBI are key biomarkers of macrophage immune injury in diabetic kidney disease.

The pathogenesis of diabetic kidney disease (DKD) is complex, and the existing treatment methods cannot control disease progression well. Macrophages play an important role in the development of DKD. This study aimed to search for biomarkers involved in immune injury induced by macrophages in DKD. The GSE96804 dataset was downloaded and analyzed by the CIBERSORT algorithm to understand the differential infiltration of macrophages between DKD and normal controls. Weighted gene co-expression network analysis was used to explore the correlation between gene expression modules and macrophages in renal tissue of DKD patients. Protein-protein interaction network and machine learning algorithm were used to screen the hub genes in the key modules. Subsequently, the GSE30528 dataset was used to further validate the expression of hub genes and analyze the diagnostic effect by the receiver operating characteristic curve. The clinical data were applied to explore the prognostic significance of hub genes. CIBERSORT analysis showed that macrophages increased significantly in DKD renal tissue samples. A total of ten modules were generated by weighted gene co-expression network analysis, of which the blue module was closely associated with macrophages. The blue module mainly played an important role in biological processes such as immune response and fibrosis. Fibronectin 1 (FN1) and transforming growth factor beta induced (TGFBI) were identified as hub genes of DKD patients. Receiver operating characteristic curve analysis was performed in the test cohort: FN1 and TGFBI had larger area under the curve values (0.99 and 0.88, respectively). Clinical validation showed that 2 hub genes were negatively correlated with the estimated glomerular filtration rate in DKD patients. In addition, FN1 and TGFBI showed a strong positive correlation with macrophage alternative activation. FN1 and TGFBI are promising biomarkers for the diagnosis and treatment of DKD patients, which may participate in immune response and fibrosis induced by macrophages.

Characterizing the Complete Mitochondrial Genomes of Three Bugs (Hemiptera: Heteroptera) Harming Bamboo.

Herein, we report the mitochondrial genomic characteristics of three insect pests, Notobitus meleagris, Macropes harringtonae, and Homoeocerus bipunctatus, collected from bamboo plants in Guizhou Province, China. For the first time, the damaged conditions and life histories of M. harringtonae and H. bipunctatus are described in detail and digital photographs of all their life stages are provided. Simultaneously, the mitochondrial genome sequences of three bamboo pests were sequenced and analyzed. Idiocerus laurifoliae and Nilaparvata lugens were used as outgroups, and the phylogenetic trees were constructed. The mitochondrial genomes of the three bamboo pests contained 37 classical genes, including 13 protein-coding genes (PCGs), two ribosomal RNA genes (rRNAs), 22 transfer RNAs (tRNAs), and a control region, with a total length of 16,199 bp, 15,314 bp, and 16,706 bp, respectively. The A+T values of the three bamboo pests were similar, and trnS1 was a cloverleaf structure with missing arms. The phylogenetic analyses, using the Bayesian inference (BI) and Maximum likelihood (ML), supported that N. meleagris and H. bipunctatus belonged to the Coreoidea family, whereas M. harringtonae belonged to the Lygaeoidea family with high support values. This study involves the first complete sequencing of the mitochondrial genomes of two bamboo pests. By adding these newly sequenced mitochondrial genome data and detailed descriptions of life histories, the database of bamboo pests is improved. These data also provide information for the development of bamboo pest control methods by quick identification techniques and the use of detailed photographs.

Comparison of Wired and Wireless Heart Rate Monitoring in the Neonatal Intensive Care Unit.

In the Neonatal Intensive Care Unit (NICU), infants' vital signs are monitored on a continuous basis via wired devices. These often interfere with patient care and pose increased risks of skin damage, infection, and tangling around the body. Recently, a wireless system for neonatal monitoring called ANNEⓇ One (Sibel Health, Chicago, USA) was developed. We designed an ongoing study to evaluate the feasibility, reliability and accuracy, of using this system in the NICU. Vital signals were simultaneously acquired by using the standard, wired clinical monitor and the ANNEⓇ device. Data from 10 NICU infants were recorded for 8 hours per day during 4 consecutive days. Initial analysis of the heart rate (HR) data revealed four problems in comparing the signals: 1) gaps in the signals - periods of time for which data were unavailable, 2) wired and wireless signals were sampled at different rates, 3) a delay between the sampled values of wired and wireless signals, and 4) this delay increased with time. To address these problems, we developed a pre-processing algorithm that interpolated samples in short gaps, resampled the signals to an equal rate, estimated the delay and drift rate between corresponding signals, and aligned the signals. Applications of the pre-processing algorithm to 40 recordings demonstrated that it was very effective. A strong agreement between wireless and wired HR signals was seen, with an average correlation of 0.95±0.04, a slope of 1.00, and a variance accounted for 89.56±7.62%. Bland-Altman analysis showed a low bias across the ensemble, with an average difference of 0.11 (95% confidence interval of -0.02 to 0.24) bpm.Clinical relevance- This algorithm provides the means for a detailed comparison of wired and wireless monitors in the NICU.

The use of wireless sensors in the neonatal intensive care unit: a study protocol.

Background: Continuous monitoring of vital signs and other biological signals in the Neonatal Intensive Care Unit (NICU) requires sensors connected to the bedside monitors by wires and cables. This monitoring system presents challenges such as risks for skin damage or infection, possibility of tangling around the patient body, or damage of the wires, which may complicate routine care. Furthermore, the presence of cables and wires can act as a barrier for parent-infant interactions and skin to skin contact. This study will investigate the use of a new wireless sensor for routine vital monitoring in the NICU. Methods: Forty-eight neonates will be recruited from the Montreal Children's Hospital NICU. The primary outcome is to evaluate the feasibility, safety, and accuracy of a wireless monitoring technology called ANNE® One (Sibel Health, Niles, MI, USA). The study will be conducted in 2 phases where physiological signals will be acquired from the standard monitoring system and the new wireless monitoring system simultaneously. In phase 1, participants will be monitored for 8 h, on four consecutive days, and the following signals will be obtained: heart rate, respiratory rate, oxygen saturation and skin temperature. In phase 2, the same signals will be recorded, but for a period of 96 consecutive hours. Safety and feasibility of the wireless devices will be assessed. Analyses of device accuracy and performance will be accomplished offline by the biomedical engineering team. Conclusion: This study will evaluate feasibility, safety, and accuracy of a new wireless monitoring technology in neonates treated in the NICU.