A comprehensive study on machine learning models combining with oversampling for bronchopulmonary dysplasia-associated pulmonary hypertension in very preterm infants.

BACKGROUND: Bronchopulmonary dysplasia-associated pulmonary hypertension (BPD-PH) remains a devastating clinical complication seriously affecting the therapeutic outcome of preterm infants. Hence, early prevention and timely diagnosis prior to pathological change is the key to reducing morbidity and improving prognosis. Our primary objective is to utilize machine learning techniques to build predictive models that could accurately identify BPD infants at risk of developing PH. METHODS: The data utilized in this study were collected from neonatology departments of four tertiary-level hospitals in China. To address the issue of imbalanced data, oversampling algorithms synthetic minority over-sampling technique (SMOTE) was applied to improve the model. RESULTS: Seven hundred sixty one clinical records were collected in our study. Following data pre-processing and feature selection, 5 of the 46 features were used to build models, including duration of invasive respiratory support (day), the severity of BPD, ventilator-associated pneumonia, pulmonary hemorrhage, and early-onset PH. Four machine learning models were applied to predictive learning, and after comprehensive selection a model was ultimately selected. The model achieved 93.8% sensitivity, 85.0% accuracy, and 0.933 AUC. A score of the logistic regression formula greater than 0 was identified as a warning sign of BPD-PH. CONCLUSIONS: We comprehensively compared different machine learning models and ultimately obtained a good prognosis model which was sufficient to support pediatric clinicians to make early diagnosis and formulate a better treatment plan for pediatric patients with BPD-PH.

Multiple on-line active valves based centrifugal microfluidics for dynamic solid-phase enrichment and purification of viral nucleic acid.

Point of care testing (POCT) of nucleic acids holds significant importance in the realm of infectious disease prevention and control, as well as the advancement of personalized precision medicine. Nevertheless, conventional nucleic acid testing methods continue to face challenges such as prolonged detection times and dependence on extensive specialized equipment and personnel, rendering them unsuitable for point of care applications. Here, we proposed an innovative active centrifugal microfluidic system (ACMS) for automatic nucleic acid extraction, encompassing modules for active valve control and magnetic control. An on-chip centrifugal puncture valve (PV) was devised based on the elastic tolerance differences between silicone membranes and tinfoils to release pre-embedded liquid reagents on demand. Furthermore, we have utilized the returnable valve (RV) technology to accurately control the retention and release of liquids, leveraging the high elastic tolerance of the silicone membrane. By incorporating an online controllable magnetic valve, we have achieved controlled and rapid aggregation and dispersion of magnetic beads. The final chip encapsulates multiple reagents and magnetic beads necessary for nucleic acid extraction. Upon sample addition and loading into the instrument, automated on-chip sample loading and nucleic acid extraction, purification, and collection can be accomplished within 30 minutes, halving the overall operation time and even increasing the efficiency of pseudovirus extraction by three orders of magnitude. Consequently, real-time fluorescence quantitative PCR amplification has successfully detected multiple targets of the SARS-CoV-2 virus (with an impressive detection limit as low as 10 copies per µL), along with targeted sequencing analysis yielding a conformity rate of 99%.

Fully integrated and automated centrifugal microfluidic chip for point-of-care multiplexed molecular diagnostics.

Public health events caused by pathogens have imposed significant economic and societal burdens. However, conventional methods still face challenges including complex operations, the need for trained operators, and sophisticated instruments. Here, we proposed a fully integrated and automated centrifugal microfluidic chip, also termed IACMC, for point-of-care multiplexed molecular diagnostics by harnessing the advantages of active and passive valves. The IACMC incorporates multiple essential components including a pneumatic balance module for sequential release of multiple reagents, a pneumatic centrifugation-assisted module for on-demand solution release, an on-chip silicon membrane module for nucleic acid extraction, a Coriolis force-mediated fluid switching module, and an amplification module. Numerical simulation and visual validation were employed to iterate and optimize the chip's structure. Upon sample loading, the chip automatically executes the entire process of bacterial sample lysis, nucleic acid capture, elution quantification, and isothermal LAMP amplification. By optimizing crucial parameters including centrifugation speed, direction of rotation, and silicone membrane thickness, the chip achieves exceptional sensitivity (twenty-five Salmonella or forty Escherichia coli) and specificity in detecting Escherichia coli and Salmonella within 40 min. The development of IACMC will drive advancements in centrifugal microfluidics for point-of-care testing and holds potential for broader applications in precision medicine including high-throughput biochemical analysis immune diagnostics, and drug susceptibility testing.

The impact of the HER2-low status on conditional survival in patients with breast cancer.

Introduction: With recent advances in breast cancer (BC) treatment, the disease-free survival (DFS) of patients is increasing and the risk factors for recurrence and metastasis are changing. However, a dynamic approach to assessing the risk of recurrent metastasis in BC is currently lacking. This study aimed to develop a dynamically changing prediction model for recurrent metastases based on conditional survival (CS) analysis. Methods: Clinical and pathological data from patients with BC who underwent surgery at the Affiliated Hospital of Qingdao University between August 2011 and August 2022 were retrospectively analysed. The risk of recurrence and metastasis in patients with varying survival rates was calculated using CS analysis, and a risk prediction model was constructed. Results: A total of 4244 patients were included in this study, with a median follow-up of 83.16 ± 31.59 months. Our findings suggested that the real-time DFS of patients increased over time, and the likelihood of DFS after surgery correlated with the number of years of prior survival. We explored different risk factors for recurrent metastasis in baseline patients, 3-year, and 5-year disease-free survivors, and found that low HER2 was a risk factor for subsequent recurrence in patients with 5-year DFS. Based on this, conditional nomograms were developed. The nomograms showed good predictive ability for recurrence and metastasis in patients with BC. Conclusion: Our study showed that the longer patients with BC remained disease-free, the greater their chances of remaining disease-free again. Predictive models for recurrence and metastasis risk based on CS analysis can help improve the confidence of patients fighting cancer and help doctors personalise treatment and follow-up plans.

Conditional survival in breast cancer With recent advances in breast cancer (BC) treatment, the disease-free survival of patients is increasing and the risk factors for recurrence and metastasis are changing. One of the key risk factor is the human epidermal growth factor receptor 2 (HER2). However, the recent advent of anti-HER2 antibody-drug conjugates (ADC) has challenged the traditional binary classification based on HER2. Patients in the traditional HER2-negative group can now be further classified as HER2-low (ISH-negative with IHC1 or IHC2) or HER2-0 (ISH-negative and IHC-0). Does this categorisation also have some value for the prognosis of BC? To figure this out, we retrospectively analysed the clinical and pathological data of BC patients who underwent surgery at the Affiliated Hospital of Qingdao University between August 2011 and August 2022. The risk of recurrence and metastasis in patients with varying survival rates was calculated using conditional survival analysis, and a risk prediction model was constructed.Our findings suggested that the real-time disease-free survival (DFS) of patients increased over time, and the likelihood of DFS after surgery correlated with the number of years of prior survival. Conditional nomograms were developed for baseline patients, 3-year and 5-year disease-free survivors. The nomograms showed good predictive ability for recurrence and metastasis in patients with BC.

Differences in the attitudes towards resuscitation of extremely premature infants between neonatologists and obstetricians: a survey study in China.

Objectives: Neonatologists and obstetricians are crucial decision-makers regarding the resuscitation of extremely preterm infants (EPIs). However, there is a scarcity of research regarding the differing perspectives on EPI resuscitation between these medical professionals. We aim to determine the differences and influential factors of their attitudes towards EPIs resuscitation in China. Methods: This cross-sectional study was conducted in public hospitals of 31 provinces in Chinese mainland from June to July 2021. Influential factors of binary variables and those of ordinal variables were analyzed by modified Poisson regression models and multinomial logistic regression models due to the invalid parallel line assumption of ordinal logistic regression models. Results: A total of 832 neonatologists and 1,478 obstetricians who were deputy chief physicians or chief physicians participated. Compared with obstetricians, neonatologists delivered a larger proportion of infants of <28-week gestational age (87.74% vs. 84.91%) and were inclined to think it inappropriate to use 28 weeks as the cutoff of gestational age for providing full care to premature infants [63.34% vs. 31.60%, adjusted prevalence ratio = 1.61 (95% CI: 1.46-1.77)], and to suggest smaller cutoffs of gestational age and birth weight for providing EPIs resuscitation. Notably, 46.49% of the neonatologists and 19.01% of the obstetricians believed infants ≤24 weeks' gestation should receive resuscitation. Conclusions: In China, notable disparities exist in attitudes of neonatologists and obstetricians towards resuscitating EPIs. Strengthening collaboration between these two groups and revising the pertinent guidelines as soon as possible would be instrumental in elevating the resuscitation rate of EPIs.

Experience of treating congenital complete atrioventricular block with epicardial pacemaker in infants and young children: a retrospective study.

BACKGROUND: This article summarizes the treatment experience for congenital complete atrioventricular block (CCAVB) in newborns and infants, and discusses the necessity and feasibility of treating CCAVB with permanent pacemaker implantation in this population. METHODS: In this study, the clinical data and follow-up results of nine children admitted at our center with CCAVB from January 2005 to March 2023 were retrospectively analyzed. Among them, two children received early implantation of permanent pacemakers (within 1 year of age), two children received non-early implantation (1 year or older), and the remaining five children received no pacemaker implantation. CCAVB diagnosis was confirmed by clinical symptoms and clinical examinations, including electrocardiography and echocardiography before surgery. After surgery, the pacing and sensing functions of the pacemaker were observed using electrocardiography, echocardiography, and pacing threshold monitoring. A comprehensive assessment of the treatment efficacy was conducted, encompassing improvements in clinical symptoms, growth and development, as well as the absence of any additional potential complications. The children who did not receive pacemaker implantation were followed up. RESULTS: Among the four children who successfully received pacemaker implantation, one child who received non-early implantation died. For the remaining three children, the threshold level, amplitude, impedance, and minute ventilation sensor function of the pacemaker were good during the follow-up period, with a heart rate at the pacing rate. The growth and development of the aforementioned patients who received pacemaker implantation demonstrated adherence to the percentile curve, and their motor and cognitive development remained unaffected. However, among the children who did not undergo pacemaker implantation, two experienced death, while three were lost to follow-up, thereby limiting the evaluation of their long-term outcomes. CONCLUSIONS: Early implantation of an epicardial pacemaker at an early stage in newborns and infants diagnosed with CCAVB can significantly improve clinical symptoms without affecting their growth and development. These data are in line with current literature and suggest that early implantation of an epicardial pacemaker in newborns and infants diagnosed with CCAVB but further studies are needed.

Receipt of COVID-19 vaccine in preterm-born children aged 3-7 in China.

Objectives: To determine the COVID-19 vaccination rate in preterm-born children aged 3-7 in China and influential factors, identify vaccination-related adverse reactions, and clarify reasons behind parental refusal of vaccination to their children. Methods: This cross-sectional study was conducted in parents of preterm-born children aged 3-7 in different regions of China through WeChat. Results: Of 1,924 Chinese preterm-born children aged 3-7 included in this study, 1,552 (80.7%) had been vaccinated against COVID-19, with a higher vaccination rate in eastern China. Children older than 4 years, kids in kindergartens and primary schools, children living in eastern or western China, and children whose fathers had received at least one dose of a COVID-19 vaccine tended to be vaccinated against COVID-19 after adjusting for other covariates. Conversely, children living in urban areas, children whose annual family income was < 50,000 CNY or more than 300,000 CNY, premature children who underwent hospital transfers, and children with underlying diseases were less likely to get vaccinated. Adverse reactions occurred in 59/1,552 (3.8%) vaccinated children. Parents of 118/372 (31.7%) children expressed their concerns over adverse reactions to COVID-19 vaccination. Other reasons like the absence of information about the place where they could get vaccination were mentioned as well. Conclusions: COVID-19 vaccination-related adverse reactions rarely occurred and most of them were mild among preterm-born children aged 3-7. Higher vaccination coverage can be achieved as parents are provided with more scientific data about benefits of vaccination, vaccination contraindications and precautions, and more information about vaccination sites.

Clinicopathological characteristics and prognosis of early-stage HER2 low-expression breast cancer: A single-center retrospective study.

Background: Owing to the emergence of drugs targeting human epidermal growth factor receptor 2 (HER2), remarkable prognostic enhancement has been seen for patients with HER2-positive breast carcinoma. However, anti-HER2 medicines are applicable merely to individuals with HER2-positive tumors, and the benefit for those with low HER2 expression is unclear. The DESTINY-Breast04 phase III and RC48 clinical trial results showed the benefit of antibody-drug couples for low HER2-expressing individuals with breast carcinoma, challenging the traditional dichotomy between HER2-negative and -positive tumors. Hence, the purposes of the present work are to explore the clinicopathological traits and prognostic differences in the HER2-low expression Chinese population with early-stage breast carcinoma. Methods: Data from the database of the Breast Center of the Affiliated Hospital of Qingdao University were collected from January 2008 to December 2017. We screened a total of 4,598 patients, of which 2,837 had HER2-0 tumors and 1,761 had HER2-low tumors. Additionally, clinicopathological characteristics, survival, and prognostic information were obtained. Difference comparisons were made between HER2-0 and HER2-low groups regarding the clinical traits and outcomes. Results: We enrolled 4598 patients, with the HR-positive subjects suffering from HER2-low breast carcinoma higher in proportion than the HR-negative patients. In contrast to HER2-0 tumors, the HER2-low tumors were linked to an older median age at diagnosis, T1 tumors, N1 stage, a higher Ki-67 index, as well as inferior histological grade. Insignificant inter-group difference was noted regarding overall survival (OS), although the HER2-0 group exhibited better disease-free survival (DFS) than the HER2-low group for the entire (P = 0.003), lymph node-negative (P = 0.009) and HR-positive (P = 0.007) populations. According to the multivariate regression finding, low HER2 expression was an inferior DFS prognostic factor in the HER2-negative population with early-stage breast cancer (HR,1.33;95% CI, 1.06-1.66; P = 0.013). Conclusion: The clinical traits of the HER2-low carcinomas differed from those of HER2-0 tumors. Despite the insignificant inter-group difference in OS, the differences in DFS were found for the overall, lymph node-negative and HR-positive subjects, suggesting the possibility of HER2-low as an inferior prognostic factor for disease progression in early-stage breast cancer.

Acceptability of COVID-19 vaccination in Chinese children aged 3-7 years with bronchopulmonary dysplasia.

OBJECTIVES: To describe the status of coronavirus disease 2019 (COVID-19) vaccination with inactivated vaccines BBIBP-CorV and CoronaVac in Chinese children aged 3-7 years with bronchopulmonary dysplasia (BPD), and explore factors influencing vaccination and reasons for nonvaccination. METHODS: This cross-sectional study involving parents of 397 BPD children aged 3-7 years was conducted through WeChat or follow-up telephone interviews using a standardized questionnaire form. Factors influencing COVID-19 vaccination were explored by using modified Poisson regression models. RESULTS: The overall COVID-19 vaccination rate was 69.0% (95% confidence interval: 64.3%-73.4%). COVID-19 vaccination was less likely to be accepted in children whose mothers had a relatively high educational background (university and above), who lived in urban areas and had a low birth weight (<1 kg), a history of hospitalization for lung diseases in the past 12 months, and intellectual disability. Conversely, kindergarten students and children from families with an annual income of >300,000 CNY ( ≈ $\approx $ 41,400 USD) were more likely to accept vaccination. Adverse reactions occurred in 13/274 children (4.7%) within 10 days after vaccination. With respect to reasons of not accepting COVID-19 vaccination, 95 parents (77.2%) worried about the adverse reactions, and 17 parents (13.8%) refused vaccination on the excuse of not being convenient to go to the vaccination station or not knowing where to get the vaccines. CONCLUSIONS: The COVID-19 vaccination rate in BPD children aged 3-7 years needs to be further improved in China. Continuous efforts are required to monitor postvaccination adverse reactions in BPD children, and make vaccination more convenient and accessible.

Obstetricians' Attitudes Toward the Treatment of Extremely Preterm Infants in China.

Importance: Extremely preterm infants (EPIs) are at high risk of mortality and disability, and whether obstetricians are active in treating EPIs is directly related to whether EPIs can get an opportunity to enter the neonatal intensive care unit (NICU) for treatment. A greater understanding of the attitudes of obstetricians toward the treatment of EPIs is needed to improve treatment of this population and optimize pediatric health policies and services. Objective: To clarify the attitudes of obstetricians toward the treatment of EPIs in China. Design, Setting, and Participants: A cross-sectional, online, questionnaire-based survey was conducted among obstetricians from various provinces and cities in China through the wenjuanxing application (a survey platform) between June and July 2021. The questionnaire included characteristics of the participants, their experiences in delivering EPIs, their attitudes toward EPI resuscitation, and their opinions about the cutoff for providing full care to preterm infants in China. Possible factors associated with their attitudes toward the cutoff for providing full care to preterm infants were analyzed by logistic regression. Data analysis was performed from August 2021 to January 2022. Main Outcomes and Measures: The attitudes of obstetricians toward the resuscitation and treatment of EPIs, and the current cutoff for providing full care to premature infants. Results: A total of 2817 valid questionnaires were recovered from 30 provinces and cities in mainland China. Of the 2817 obstetricians (mean [SD] age, 41.76 [8.50] years) investigated, 156 (5.5%) were male, 2661 (94.5%) were female, 1339 (47.5%) were deputy chief physicians or chief physicians, 1662 (59.0%) were from tertiary hospitals, and 2048 (72.7%) had experience in delivering EPIs. The proportion of obstetricians who supported resuscitation of preterm infants was 19.1% (539 respondents) at a gestational age 24 weeks, 24.1% (679 respondents) at 25 weeks, 54.8% (1543 respondents) at 26 weeks, and 100.0% (2817 respondents) at 27 weeks. A total of 1326 obstetricians (47.1%) reported that it was common or very common for EPIs to be withdrawn from resuscitation and not to be admitted to the NICU for treatment. Regarding the treatment of EPIs with higher possibility of survival, 1621 obstetricians (57.5%) maintained that appropriate information should be communicated but their parents' wishes should be respected. Most obstetricians (2051 respondents [72.8%]) maintained that 28 weeks was the cutoff for providing full care to preterm infants in China; 766 respondents (27.2%) thought of it as inappropriate, suggesting the cutoff should be less than 28 weeks. Logistic regression analysis showed that these differences were significantly associated with the professional titles of the obstetricians, geographical regions, hospital levels and types, whether they had any experience in delivering EPIs, and the total number of EPIs born yearly in their units. Conclusions and Relevance: In this cross-sectional study, most Chinese obstetricians maintained a conservative attitude toward the treatment of EPIs. It was very common for EPIs to be withdrawn from treatment without entering the NICU directly after birth. Most obstetricians maintained that 28 weeks' gestational age should be the cutoff for providing full care to premature infants.

Correlation between microbiota and flavours in fermentation of Chinese Sichuan Paocai.

Sichuan Paocai (SCP), a traditional fermentationed food, possesses unique flavours driven by various microbiota in fermentation ecosystems. However, the association between these microbiota and flavours is poorly understood. Here, we measured the structural dynamics of the microbial diversity and flavour compounds during SCP fermentation (0-7 days) using high-throughput sequencing and flavour analyses. Firstly, a total of 90 bacteria and 135 fungi were identified. The results showed that fermentation process was initiated by environmental microorganisms, such as Micrococcaceae, followed by a heterolactic fermentation phase dominated by Leuconostocaceae, and finally succeeded by homolactic fermentation led by Lactobacillaceae. Secondly, 6 organic acids, 12 amino acids and 86 volatile flavours were detected. The fermentation process was divided into 4 stages based on flavours: Day 0; Days 1-3; Days 4-6; and Day 7. Analysis of the correlation between microbiota and flavours indicated that bacteria contributed more to flavours formation than did fungi, and Lactobacillus, Leuconostoc, Achromobacter and Pediococcus were closely correlated with flavours. This study provides a systematic method for understanding the characteristics of fermented foods and useful guidelines for screening of strains that produce desirable flavours and functional substances.

Efficacy of Toric intraocular lens implantation in eyes with high myopia: A prospective, case-controlled observational study.

The present prospective clinical observational study aimed to evaluate the efficacy of Toric intraocular lenses (IOL) to achieve rotational stability and astigmatism correction in eyes with high myopia. A total of 27 consecutive cataract patients (39 eyes) with pre-existing corneal astigmatism (1.5-3.5 D) were divided into two groups according to their refractive status: One group of 18 eyes with high myopia -(12.5-6.0 D) and another group consisting of 21 eyes with emmetropia or low myopia (-3.0-0.0 D). All eyes underwent cataract phacoemulsification surgeries by the same surgeon, with the implantation of an AcrySof® Toric IOL at the pre-designed degree. Uncorrected visual acuity, best corrected visual acuity and phoropter examination results were recorded at the 1st day, 1st week, 1st month and 3rd month after the surgery. By analyzing digital images from slim-lamp photography with a self-designed software, the rotational stability was observed. The contrast sensitivity was also measured. No significant difference in the baseline and post-operative residual astigmatism was identified between the two groups (P>0.05). In addition, no significant difference in the degree of rotation was observed between the two groups. All patients had significantly improved visual quality after the surgery (P<0.05). In conclusion, the present study observed an equal astigmatism-correction efficiency and rotational stability in the two groups. A second auxiliary spot-penetrating incision, removal of visco-elastic substances and tight adherence of the IOL to the posterior capsular membrane are essential for a successful surgery.