Automatic Nonnutritive Suck Waveform Discrimination and Feature Extraction in Preterm Infants

Background and Objective: The emergence of the nonnutritive suck (NNS) pattern in preterm infants reflects the integrity of the brain and is used by clinicians in the neonatal intensive care unit (NICU) to assess feeding readiness and oromotor development. A critical need exists for an integrated software platform that provides NNS signal preprocessing, adaptive waveform discrimination, feature detection, and batch processing of big data sets across multiple NICU sites. Thus, the goal was to develop and describe a crossplatform graphical user interface (GUI) and terminal application known as NeoNNS for single and batch file time series and frequency-domain analyses of NNS compression pressure waveforms using analysis parameters derived from previous research on NNS dynamics. Methods. NeoNNS was implemented with Python and the Tkinter GUI package. The NNS signal-processing pipeline included a low-pass filter, asymmetric regression baseline correction, NNS peak detection, and NNS burst classification. Data visualizations and parametric analyses included time- and frequency-domain view, NNS spatiotemporal index view, and feature cluster analysis to model oral feeding readiness. Results. 568 suck assessment files sampled from 30 extremely preterm infants were processed in the batch mode (\u3c50 minutes) to generate time- and frequency-domain analyses of infant NNS pressure waveform data. NNS cycle discrimination and NNS burst classification yield quantification of NNS waveform features as a function of postmenstrual age. Hierarchical cluster analysis (based on the Tsfresh python package and NeoNNS) revealed the capability to label NNS records for feeding readiness. Conclusions. NeoNNS provides a versatile software platform to rapidly quantify the dynamics of NNS development in time and frequency domains at cribside over repeated sessions for an individual baby or among large numbers of preterm infants at multiple hospital sites to support big data analytics. The hierarchical cluster feature analysis facilitates modeling of feeding readiness based on quantitative features of the NNS compression pressure waveform

Automatic Nonnutritive Suck Waveform Discrimination and Feature Extraction in Preterm Infants

Background and Objective: +e emergence of the nonnutritive suck (NNS) pattern in preterm infants reflects the integrity of the brain and is used by clinicians in the neonatal intensive care unit (NICU) to assess feeding readiness and oromotor development. A critical need exists for an integrated software platform that provides NNS signal preprocessing, adaptive waveform discrimination, feature detection, and batch processing of big data sets across multiple NICU sites. +us, the goal was to develop and describe a crossplatform graphical user interface (GUI) and terminal application known as NeoNNS for single and batch file time series and frequency-domain analyses of NNS compression pressure waveforms using analysis parameters derived from previous research on NNS dynamics. Methods. NeoNNS was implemented with Python and the Tkinter GUI package. +e NNS signal-processing pipeline included a low-pass filter, asymmetric regression baseline correction, NNS peak detection, and NNS burst classification. Data visualizations and parametric analyses included time- and frequency-domain view, NNS spatiotemporal index view, and feature cluster analysis to model oral feeding readiness. Results. 568 suck assessment files sampled from 30 extremely preterm infants were processed in the batch mode (\u3c50 minutes) to generate time- and frequency-domain analyses of infant NNS pressure waveform data. NNS cycle discrimination and NNS burst classification yield quantification of NNS waveform features as a function of postmenstrual age. Hierarchical cluster analysis (based on the Tsfresh python package and NeoNNS) revealed the capability to label NNS records for feeding readiness. Conclusions. NeoNNS provides a versatile software platform to rapidly quantify the dynamics of NNS development in time and frequency domains at cribside over repeated sessions for an individual baby or among large numbers of preterm infants at multiple hospital sites to support big data analytics. +e hierarchical cluster feature analysis facilitates modeling of feeding readiness based on quantitative features of the NNS compression pressure waveform

Amplitude-Integrated EEG and Range-EEG Modulation Associated with Pneumatic Orocutaneous Stimulation in Preterm Infants

Background—Controlled somatosensory stimulation strategies have demonstrated merit in developing oral feeding skills in premature infants who lack a functional suck, however, the effects of orosensory entrainment stimulation on electrocortical dynamics is unknown. Objective—To determine the effects of servo-controlled pneumatic orocutaneous stimulation presented during gavage feedings on the modulation of aEEG and rEEG activity. Methods—Two-channel EEG recordings were collected during 180 sessions that included orocutaneous stimulation and non-stimulation epochs among 22 preterm infants (mean gestational age = 28.56 weeks) who were randomized to treatment and control ‘sham’ conditions. The study was initiated at around 32 weeks post-menstrual age (PMA). The raw EEG was transformed into amplitude-integrated EEG (aEEG) margins, and range-EEG (rEEG) amplitude bands measured at 1-minute intervals and subjected to a mixed models statistical analysis. Results—Multiple significant effects were observed in the processed EEG during and immediately following 3-minute periods of orocutaneous stimulation, including modulation of the upper and lower margins of the aEEG, and a reorganization of rEEG with an apparent shift from amplitude bands D and E to band C throughout the 23-minute recording period that followed the first stimulus block when compared to the sham condition. Cortical asymmetry also was apparent in both EEG measures. Conclusions—Orocutaneous stimulation represents a salient trigeminal input which has both short- and long-term effects in modulating electrocortical activity, and thus, is hypothesized to represent a form of neural adaptation or plasticity that may benefit the preterm infant during this critical period of brain maturation

Amplitude-Integrated EEG and Range-EEG Modulation Associated with Pneumatic Orocutaneous Stimulation in Preterm Infants

Background—Controlled somatosensory stimulation strategies have demonstrated merit in developing oral feeding skills in premature infants who lack a functional suck, however, the effects of orosensory entrainment stimulation on electrocortical dynamics is unknown. Objective—To determine the effects of servo-controlled pneumatic orocutaneous stimulation presented during gavage feedings on the modulation of aEEG and rEEG activity. Methods—Two-channel EEG recordings were collected during 180 sessions that included orocutaneous stimulation and non-stimulation epochs among 22 preterm infants (mean gestational age = 28.56 weeks) who were randomized to treatment and control ‘sham’ conditions. The study was initiated at around 32 weeks post-menstrual age (PMA). The raw EEG was transformed into amplitude-integrated EEG (aEEG) margins, and range-EEG (rEEG) amplitude bands measured at 1-minute intervals and subjected to a mixed models statistical analysis. Results—Multiple significant effects were observed in the processed EEG during and immediately following 3-minute periods of orocutaneous stimulation, including modulation of the upper and lower margins of the aEEG, and a reorganization of rEEG with an apparent shift from amplitude bands D and E to band C throughout the 23-minute recording period that followed the first stimulus block when compared to the sham condition. Cortical asymmetry also was apparent in both EEG measures. Conclusions—Orocutaneous stimulation represents a salient trigeminal input which has both short- and long-term effects in modulating electrocortical activity, and thus, is hypothesized to represent a form of neural adaptation or plasticity that may benefit the preterm infant during this critical period of brain maturation

Modulation of EEG spectral edge frequency during patterned pneumatic oral stimulation in preterm infants

Background—Stimulation of the nervous system plays a central role in brain development and neurodevelopmental outcome. Thalamocortical and corticocortical development is diminished in premature infants and correlated to electroencephalography (EEG) progression. The purpose of this study was to determine the effects of orocutaneous stimulation on the modulation of spectral edge frequency, fc=90% (SEF-90) derived from EEG recordings in preterm infants. Methods—Twenty two preterm infants were randomized to experimental and control conditions. Pulsed orocutaneous stimulation was presented during gavage feedings begun at around 32 weeks postmenstrual age (PMA). The SEF-90 was derived from 2-channel EEG recordings. Results—Compared to the control condition, the pulsed orocutaneous stimulation produced a significant reorganization of SEF-90 in the left (p = 0.005) and right (p \u3c 0.0001) hemispheres. Notably, the left and right hemisphere showed a reversal in the polarity of frequency shift, demonstrating hemispheric asymmetry in the frequency domain. Pulsed orocutaneous stimulation also produced a significant pattern of short term cortical adaptation and a long term neural adaptation manifest as a 0.5 Hz elevation in SEF-90 after repeated stimulation sessions. Conclusion—This is the first study to demonstrate the modulating effects of a servo-controlled oral somatosensory input on the spectral features of EEG activity in preterm infants

Neutralization of IL- 10 produced by B cells promotes protective immunity during persistent HCV infection in humanized mice

Chronic HCV infection can lead to cirrhosis and is associated with increased mortality. Interleukin (IL)- 10- producing B cells (B10 cells) are regulatory cells that suppress cellular immune responses. Here, we aimed to determine whether HCV induces B10 cells and assess the roles of the B10 cells during HCV infection. HCV- induced B10 cells were enriched in CD19hi and CD1dhiCD5+ cell populations. HCV predominantly triggered the TLR2- MyD88- NF- κB and AP- 1 signaling pathways to drive IL- 10 production by B cells. In a humanized murine model of persistent HCV infection, to neutralize IL- 10 produced by B10 cells, mice were treated with pcCD19scFv- IL- 10R, which contains the genes coding the anti- CD19 single- chain variable fragment (CD19scFv) and the extracellular domain of IL- 10 receptor alpha chain (sIL- 10Ra). This treatment resulted in significant reduction of B10 cells in spleen and liver, increase of cytotoxic CD8+ T- cell responses against HCV, and low viral loads in infected humanized mice. Our results indicate that targeting B10 cells via neutralization of IL- 10 may offer a novel strategy to enhance anti- HCV immunotherapy.HCV predominantly triggers the TLR2- MyD88- NF- κB and AP- 1 signaling pathways to drive IL- 10 production by B cells. Neutralization of IL- 10 produced by B10 cells promotes anti- HCV immunity in a humanized murine model of persistent HCV infection. These results provide insight into a novel immunotherapy strategy for HCV treatment.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/162732/2/eji4736.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/162732/1/eji4736_am.pd

Defining the threshold: triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio’s non-linear impact on tubular atrophy in primary membranous nephropathy

BackgroundHyperlipidemia is common in primary membranous nephropathy (PMN) patients, and tubular atrophy (TA) is an unfavorable prognostic factor. However, the correlation between the triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio and TA is controversial. Therefore, our study aimed to investigate the association between the TG/HDL-C ratio and TA in PMN patients.MethodsWe conducted a cross-sectional study and collected data from 363 PMN patients at Shenzhen Second People’s Hospital from January 2008 to April 2023. The primary objective was to evaluate the independent correlation between the TG/HDL-C ratio and TA using binary logistic regression model. We used a generalized additive model along with smooth curve fitting and multiple sensitivity analyses to explore the relationship between these variables. Additionally, subgroup analyses were conducted to delve deeper into the results.ResultsOf the 363 PMN patients, 75 had TA (20.66%). The study population had a mean age of 46.598 ± 14.462 years, with 217 (59.78%) being male. After adjusting for sex, age, BMI, hypertension, history of diabetes, smoking, alcohol consumption, UPRO, eGFR, HB, FPG, and ALB, we found that the TG/HDL-C ratio was an independent risk factor for TA in PMN patients (OR=1.29, 95% CI: 1.04, 1.61, P=0.0213). A non-linear correlation was observed between the TG/HDL-C ratio and TA, with an inflection point at 4.25. The odds ratios (OR) on the left and right sides of this inflection point were 1.56 (95% CI: 1.17, 2.07) and 0.25 (95% CI: 0.04, 1.54), respectively. Sensitivity analysis confirmed these results. Subgroup analysis showed a consistent association between the TG/HDL-C ratio and TA, implying that factors such as gender, BMI, age, UPRO, ALB, hypertension and severe nephrotic syndrome had negligible effects on the link between the TG/HDL-C ratio and TA.ConclusionOur study demonstrates a non-linear positive correlation between the TG/HDL-C ratio and the risk of TA in PMN patients, independent of other factors. Specifically, the association is more pronounced when the ratio falls below 4.25. Based on our findings, it would be advisable to decrease the TG/HDL-C ratio below the inflection point in PMN patients as part of treatment strategies

The GECAM Real-Time Burst Alert System

Gravitational Wave High-energy Electromagnetic Counterpart All-sky Monitor (GECAM), consisting of two micro-satellites, is designed to detect gamma-ray bursts associated with gravitational-wave events. Here, we introduce the real-time burst alert system of GECAM, with the adoption of the BeiDou-3 short message communication service. We present the post-trigger operations, the detailed ground-based analysis, and the performance of the system. In the first year of the in-flight operation, GECAM was triggered by 42 GRBs. GECAM real-time burst alert system has the ability to distribute the alert within $\sim$1 minute after being triggered, which enables timely follow-up observations.Comment: 17 pages, 10 figures; Accepted for publication in RA

Perioperative dynamic alterations in peripheral regulatory T and B cells in patients with hepatocellular carcinoma

<p>Abstract</p> <p>Background</p> <p>Intratumoral and circulating regulatory T cells (Tregs) have been shown to be critical in the pathogenesis of hepatocellular carcinoma (HCC). However there is limited knowledge on the alterations of regulatory B cells (Bregs). We here investigated perioperative dynamic alterations of peripheral circulating Tregs and Bregs in HCC patients to reveal the relationship between regulatory lymphocytes and its clinical implications.</p> <p>Methods</p> <p>36 patients with HCC, 6 with chronic hepatitis B infection and 10 healthy donors were enrolled for this study. Frequencies of peripheral Tregs and Bregs were measured by flow cytometry with antibodies against CD4, CD25, CD127, CD19 and IL-10 before, and after radical surgery. Then, clinical informatics of HCC patients was achieved through Digital Evaluation Score System (DESS) for the assessment of disease severity. Finally, we analysed correlations between digitalized clinical features and kinetics of circulating regulatory lymphocytes.</p> <p>Results</p> <p>Level of circulating CD4⁺CD25⁺CD127^-Tregs in HCC patients was significantly lower than that in healthy donors and patients with chronic hepatitis B infection before surgery, but was increased after surgery. Preoperative level of CD19⁺IL-10⁺Bregs in HCC patients was also significantly lower than the other groups. However it dramatically was elevated right after surgery and remained elevated compared to controls (about 7 days after surgery, <it>P </it>= 0.04). Frequency of circulating Tregs was correlated with circulating leukocytes, ferritin, and clinical features suggesting tumor aggressiveness including portal vein thrombosis, hepatic vein involvement and advanced clinical stages. Frequency of circulating Bregs was associated with Hepatitis B e Antigen (HBeAg) and Hepatitis B virus (HBV) DNA copy number. In addition, DESS was significantly and positively correlated with other staging systems.</p> <p>Conclusion</p> <p>Frequencies of peripheral Tregs and Bregs in HCC patients increased after surgery. These results suggest that a postoperative combination of therapies against Tregs and Bregs may be beneficial for better outcome of HCC patients after resection.</p