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Pneumonia is the leading cause of infectious related death costing 12 billion dollars annually in the United States alone. Despite improvements in clinical care, total mortality remains around 4%, with inpatient mortality reaching 5-10%. For unknown reasons, mortality risk remains high even after hospital discharge and there is a need to identify those patients most at risk. Also of importance, clinical symptoms alone do not distinguish viral from bacterial infection which may delay appropriate treatment and may contribute to short-term and long-term mortality. Biomarkers have the potential to provide point of care diagnosis, identify high-risk patients, and increase our understanding of the biology of disease. However, there have been mixed results on the diagnostic performance of many of the analytes tested to date. Urine represents a largely untapped source for biomarker discovery and is highly accessible. To test this hypothesis, we collected urine from hospitalized patients with community-acquired pneumonia (CAP) and performed a comprehensive screen for urinary tract microbiota signatures, metabolite, and cytokine profiles. CAP patients were diagnosed with influenza or bacterial (S. aureus and S. pneumoniae) etiologies and compared with healthy volunteers. Microbiome signatures showed marked shifts in taxonomic levels in patients with bacterial etiology versus influenza and CAP versus normal. Predictive modeling of 291 microbial and metabolite values achieved a +90% accuracy with LASSO in predicting specific pneumonia etiology. This study demonstrates that urine from patients hospitalized with pneumonia may serve as a reliable and accessible sample to evaluate biomarkers that may diagnose etiology and predict clinical outcomes.Author SummaryUrine has been classically considered sterile since most microorganisms are not readily culturable under healthy circumstances. Further, many pneumonia patients are immediately placed on antibiotics rendering culture-based techniques useless. However, the advent of next generation sequencing has enabled unprecedented analysis of the microbial communities – living or detected as free DNA – found in many niches of the human body. Here, we describe a urine microbiome as well as metabolites and cytokines measured in patients newly admitted to the hospital diagnosed with influenza or bacterial (S. aureus and S. pneumoniae) infection pneumonia, compared with healthy controls. Using these parameters alone, we were able to achieve high success in predicting patient pneumonia. This study provides a proof of concept that urine samples, which are easily accessible in outpatient and inpatient settings, could provide additional diagnostic insights to patient infectious status and future risk factor for complication.

When assembling individual quantum components into a mesoscopic circuit, the interplay between Coulomb interaction and charge granularity breaks down the classical laws of electrical impedance composition. Here we explore experimentally the thermal consequences, and observe an additional quantum mechanism of electronic heat transport. The investigated, broadly tunable test-bed circuit is composed of a micron-scale metallic node connected to one electronic channel and a resistance. Heating up the node with Joule dissipation, we separately determine, from complementary noise measurements, both its temperature and the thermal shot noise induced by the temperature difference across the channel (`delta-$T$ noise'). The thermal shot noise predictions are thereby directly validated, and the electronic heat flow is revealed. The latter exhibits a contribution from the channel involving the electrons' partitioning together with the Coulomb interaction. Expanding heat current predictions to include the thermal shot noise, we find a quantitative agreement with experiments., Minor differences with published article: additional reference [29], more explicit identification 'thermal shot noise' - 'delta-T noise', includes the supplementary figures

We investigated whether metabolic phenotype improvements following gastric bypass are associated with gastric resection strategy in high-fat diet-induced obese (DIO) mice.We developed the mouse Roux-en-Y gastric bypass (RYGB) model with different gastric pouch sizes: (i) RYGB with a large gastric pouch (RYGB-LP), where the stomach was transected, and the jejunum was anastomosed to the residual forestomach, in which 30% of the stomach is retained. (ii) RYGB with a small remnant gastric pouch (RYGB-SP), where the stomach was transected 0.8 cm distal to the esophagogastric junction, and the jejunum is attached to a small remnant of the forestomach (~ 10% of the stomach). (iii) RYGB without gastric pouch (RYGB-NP), where the jejunum is anastomosed to the lower portion of the esophagus.Surgical success rate (or 4-week mouse survival rate) of the RYGB-LP, RYGB-SP, and RYGB-NP procedures was 50, 75, and 85%, respectively. Our data demonstrate that all RYGB procedures improved body weight, glucose tolerance, and liver steatosis, compared with untreated DIO mice at 8-week post-surgery. Major surgical complication, such as obstruction at the forestomach, occurred predominantly in RYGB-LP mice, resulting in a higher mortality. Pre- and post-prandial plasma ghrelin levels did not correlate with improved metabolic phenotype after gastric bypass.We conclude that RYGB with different gastric pouch equally improves obesity and glucose tolerance independent of gastric pouch size and total plasma ghrelin levels in the mouse model of RYGB surgery.

We review the intriguing many-body physics resulting out of the interplay of a single, local impurity and the two-particle interaction in a one-dimensional Fermi system. Even if the underlying homogeneous correlated system is taken to be metallic, this interplay leads to an emergent quantum phase transition between metallic and insulating states. We show that the zero temperature critical point and the universal low-energy physics associated to it, is realized in two different models, the field theoretical local sine-Gordon model and spinless fermions on a lattice with nearest-neighbor hopping and two-particle interaction, as well as in an experimental setup consisting of a highly tunable quantum circuit. Despite the different high-energy physics of the three systems the universal low-energy scaling curves of the conductance as a function of temperature agree up to a very high precision without any free parameter. Overall this provides a convincing example of how emergent universality in complex systems originating from a common underlying quantum critical point establishes a bridge between different fields of physics. In our case between field theory, quantum many-body theory of correlated Fermi systems, and experimental circuit quantum electrodynamics., version as accepted for publication in EPJST

Gut microbial diurnal oscillations are important diet-dependent drivers of host circadian rhythms and metabolism that ensure optimal energy balance. Yet, the interplay between diet, microbes, and host factors that sustain intestinal oscillations is complex and poorly understood. We report the host C-type lectin antimicrobial peptide REG3γ works with key ileal microbes to orchestrate these interactions in a bi-directional manner, independent from the intestinal core circadian clock. High fat diet diminishes physiologically relevant microbial oscillators essential for host metabolic homeostasis, resulting in arrhythmic host REG3γ expression and increased abundance and oscillation of REG3γ-independent gut microbes. This illustrates a transkingdom co-evolved biological rhythm involving reciprocating, sensor-effector signals between key host and microbial components that ultimately drive metabolism, but are also heavily influenced by diet. Restoring the gut microbiota’s capacity to sense and transduce dietary signals mediated by specific host factors such as REG3γ could be harnessed to improve metabolic dysfunction.

Current literature extols challenges that Black women in academia face. The evidence typically suggests lack of a critical mass of Black women in institutions are to blame for their diminished access to mentoring relationships, stifled tenure, promotion, and advancement rates, and contributes to an overall sense of isolation and overwork. Started in 2001, the Sisters of the Academy (SOTA) Institute created a network of Black women in academia. With a focus on professional development and mentoring, SOTA’s mission is to ensure that Black women thrive despite the oppression they experience in academia. Using a culturally responsive model for mentoring, the SOTA Research BootCamp serves as a professional counterspace focused on research development for early career scholars, advanced doctoral students, and junior scholars, while centering the perspectives of Black women to ground participants’ experiences. In this chapter we explore how culturally responsive mentoring serves as a model for: challenging the current deficit narrative about Black women in academia; developing culturally responsive mentors and proteges; and ensuring that Black women in academia thrive.

SUMMARY It is now accepted that the gut microbiome is an important component in shaping human and animal homeostasis and disease susceptibility. Through its diverse roles in digestion and nutrient absorption, production of essential vitamins, release of novel small molecules and metabolites, stimulation of immune development and function, and broad modulation of regulatory systems in the body ranging from endocrine to neuronal, the microbiome has proven an important frontier in our understanding of animal biology and nutrition. This chapter reviews the rise and current state of microbiome science and focuses on how nutrient interactions with our microbial organ system shape nutritional health and outcomes under numerous pathophysiological states.

Objectives: This study sought to delineate clinical phenotype and investigate pathophysiological mechanisms of arrhythmogenic right ventricular cardiomyopathy (ARVC5) in vivo.Background: Mutation p.S358L in TMEM43/LUMA causes ARVC5, a fully penetrant gender- and exercise-dependent disease. Exact pathophysiological mechanisms of ARVC5 remain incomplete and controversial. Methods: Knock-in Tmem43S358L mice were generated using conventional targeting. Assessment of cardiac and intestinal phenotypes, transcriptome and protein analysis were performed. Results: Onset of systolic dysfunction and rhythm asymmetry was apparent in 3-month-old homozygote mutants. Heterozygote 6-month-old mutants displayed systolic dysfunction as well. Biventricular myocardial fibro-fatty infiltration and subcellular abnormalities were found in both mutants, while acute stress caused ventricular tachycardia and death in homozygotes. Microarray revealed that WNT-b-catenin and PPARG signaling-associated genes were differentially expressed between LV and RV. Tmem43S358L mutants displayed significantly reduced PPARG activities and downregulation of PPARG-downstream metabolic genes in the heart. Expression of b-catenin were significantly reduced, while JUP was translocated into nuclei of mutant cardiomyocytes. Conversely in small intestine, b-catenin and PPARG-associated genes responsible for cholesterol, bile acid, and lipid transport were upregulated in Tmem43S358L mutants resulting in elevated lipids absorption, hyperlipidemia, and reciprocal fecal lipids reduction. These abnormalities were associated with elongated villi, fatty infiltrations, and gut epithelial proliferation markers in small intestine. Conclusions: We defined novel distinct effects of the TMEM43-S358L mutation on small intestine homeostasis in addition to cardiac damage. Tmem43-S358L perturbs PPARG and WNT-b-catenin signaling in the heart as well as in intestine, elevating lipids absorption from gut lumen whereby triggering ACM pathophysiology.

The phase change from the amorphous to crystalline state which occurs upon thermal annealing in prototypical Ge2Sb2Te5 and nitrogen-doped Ge2Sb2Te5 phase-change-materials (PCM) thin films is studied by concomitant, complementary and combined in situ and ex situ X-ray diffraction (XRD) and X-ray reflectivity (XRR) techniques. It is demonstrated that combined in situ X-ray scattering techniques allow accurate investigation and clarification of the structural, morphological and mechanical variations occurring in the films upon crystallization. The crystallization process is correlated with volume shrinkage (densification and thickness reduction) and with structural change with a tensile strain build-up. The comparison of Ge2Sb2Te5 and nitrogen-doped Ge2Sb2Te5 reveals a significant slowdown of the crystallization process, induced by the incorporation of nitrogen. However, the mechanisms involved in the phase change are not strongly modified by the incorporation; rather, the crystallization process is inhibited because of the presence of nitrogen. In this way, different stages of the crystallization process can be observed. The combined XRD/XRR analysis gives new insights on the stress components built up in phase-change materials. First, at the early stage of crystallization, a large hydrostatic tensile stress builds up in the PCM thin film. Afterwards, concomitant grain growth, viscous flow, densification and thickness accommodation are observed, which lead to a partial stress relaxation in the PCM films. This combined characterization technique offers a new approach that may further our understanding of the phase change involved.

These data support the findings that dietary micronutrients influence the inflammatory responses and intestinal microbial community structure and function in a model of pouchitis-like small bowel inflammation reported in “Dietary Antioxidant Micronutrients Alter Mucosal Inflammatory Risk in a Murine Model of Genetic and Microbial Susceptibility” (Pierre et al., 2018) [1]. Briefly, wild-type and IL-10 deficient mice underwent surgical placement of small intestinal self-filling loops (SFL) and were subsequently fed purified control diet (CONT) or control diet supplemented with 4 micronutrients (AOX), retinoic acid, Vitamin C, Vitamin E, and selenium, for 14 days. These data include changes in host markers, such as body weight, mucosal levels of myeloperoxidase and syndecan-1, and luminal IgA and IgG levels. These data also include changes in the microbial compartment, including 16S community structure in the self-filling loop, conventionalized germ-free mice, and microbial substrate preference performed through anaerobic bacterial culturing of SLF CONT and AOX microbiota.

Transmitting quantum states The coherence of electrons in mesoscopic structures is thought to be unlikely to survive in a disordered environment. Duprez et al. show that this is not necessarily the case. They studied a metallic island as an example of a disordered environment. They made an electron interferometer and incorporated the island in one of the two paths through the interferometer. At sufficiently low temperatures and in the quantum Hall regime, they observed a clear interference pattern, indicating successful transmission of the electrons' quantum state across the island. Science , this issue p. 1243

The objectives of this study were to implement, test adherence to and examine the preliminary effectiveness of a summertime weight-gain prevention intervention in youth from a low-income, Rhode Island community. In 2016, 51 children, ages 6–12 years, participated in a daily, summertime intervention, which offered a minimum of two hours of physical activity programming and free lunch through the USDA's Summer Food Service Program (SFSP). Thirty children from the same community with similar SFSP access served as a comparison group. Height and weight were measured before and at the end of summer to assess change in body mass index z-score (BMIz). Diet and physical activity were assessed midsummer. Multivariate mixed models were used to test group differences in change in BMIz over the summer and weight-related behaviors midsummer. Repeated measures ANOVA was used to examine the relationships of intervention participation with change in BMIz and weight-related behaviors in intervention participants. On average, intervention participants attended 65.6% of program sessions. They lost 0.04 BMIz units, while those in the comparison group gained 0.03 BMIz units (p = 0.07). Midsummer, intervention participants spent 4.6% less time sedentary on weekdays as compared to comparison participants (p = 0.03). Among intervention participants, attendance was significantly associated with change in BMIz (p = 0.01), spending 41 more minutes in moderate to vigorous physical activity (MVPA) (p = 0.004) and 8.5% less time sedentary (p, Highlights • Implementing a weight gain prevention intervention in the summer is feasible. • Findings suggest that participation was associated with reductions in BMIz. • Participants were more active and less sedentary on days they attended the program. • Preventing summer weight gain may be possible in youth from low-income communities.

Bioengineered marine microalgae Schizochytrium sp. is currently used to produce docosahexaenoic acid (DHA). However, following DHA extraction, the remaining protein-rich materials are not well utilized. In this study, we report that marine microalgae bioengineered Schizochytrium sp. hydrolysate (MESH), which exhibits a unique peptide profile as identified by Ultra Performance Liquid Chromatography coupled with Q-TOF mass spectrometry(UPLC/Q-TOF-MS), ameliorated bowel inflammation in mice. In a mouse model of experimentalcolitis induced by dextran sulfate sodium, compared with the control mice, the mice treated with MESH were highly resistant to colitis, as demonstrated by marked reductions in body weight loss, clinical colitis scores, colonic histological damage, and colonic inflammation. Mechanistically, MESH attenuated the induction of pro-inflammatory cytokines and increased the induction of anti-inflammatory cytokines. MESH also promoted the proliferation of colonic crypt stem cells and progenitor cells required for crypt repair. Collectively, these results reveal a previously unrecognized role of MESH as a potential anti-inflammatory treatment for colitis.

Somatic mutations in tet methylcytosine dioxygenase 2 (TET2), which encodes an epigenetic modifier enzyme, drive the development of haematopoietic malignancies1–7. In both humans and mice, TET2 deficiency leads to increased self-renewal of haematopoietic stem cells with a net developmental bias towards the myeloid lineage1,4,8,9. However, pre-leukaemic myeloproliferation (PMP) occurs in only a fraction of Tet2−/− mice8,9 and humans with TET2 mutations1,3,5–7, suggesting that extrinsic non-cell-autonomous factors are required for disease onset. Here we show that bacterial translocation and increased interleukin-6 production, resulting from dysfunction of the small-intestinal barrier, are critical for the development of PMP in mice that lack Tet2 expression in haematopoietic cells. Furthermore, in symptom-free Tet2−/− mice, PMP can be induced by disrupting intestinal barrier integrity, or in response to systemic bacterial stimuli such as the toll-like receptor 2 agonist. PMP was reversed by antibiotic treatment and failed to develop in germ-free Tet2−/− mice, which illustrates the importance of microbial signals in the development of this condition. Our findings demonstrate the requirement for microbial-dependent inflammation in the development of PMP and provide a mechanistic basis for the variation in PMP penetrance observed in Tet2−/− mice. This study will prompt new lines of investigation that may profoundly affect the prevention and management of haematopoietic malignancies.

Background Lung ultrasound (LU) is a bedside point-of-care technique in critical care and emergency medicine. LU is quick and non-irradiating, and provides accurate diagnostic information when compared with chest radiographs. Specific LU signs have been described for bronchiolitis. This study aimed to evaluate the correlation between severity of LU-diagnosed lung lesions, using a quantitative LU score, and the length of non-invasive ventilation (LOV) for infants diagnosed with severe viral bronchiolitis. Methods This was a prospective observational single-center study conducted at a level 3 pediatric intensive care unit. A LU score was calculated for 47 infants under 6 months of age with severe acute viral bronchiolitis during the 2015–2016 epidemic, and the number of intercostal spaces with consolidation or interstitial syndrome was counted for each lung. The LU score is based on the presence of A lines or B-line artifacts and consolidation (0–2 points). The modified Wood score (mWCAS) was used to define clinical severity. Other parameters such as gestational age at birth, age, supplemental oxygen (LOS), and length of stay were recorded. All LU scans were later reviewed by two trained ultrasonographers to assess the score's inter-rater reproducibility. Results The LU score on admission (3.5 ± 2.6) did not correlate with LOV (69 ± 68.6), mWCAS score (4 ± 1.6), LOS (3 ± 3.4), or length of stay (4 ± 3.4). However, there was a significant correlation between the number of affected intercostal spaces on the right and LOS (Spearman's Rho 0.318; P = 0.037). Conclusion This is the first study to evaluate the use of LU in infants needing PICU admission for severe acute bronchiolitis. The LU score does not correlate with LOV, mWCAS, LOS, or length of stay, but the number of pathological intercostal spaces on the right side correlates significantly with LOS. Although LU scores have been validated for the newborn and the adult, this has been in the setting of restrictive lung diseases. Bronchiolitis is a predominantly obstructive lung disease and this may explain the lack of performance observed.

BACKGROUND: The aim of this study was to assess diagnosis severity, perioperative management and outcomes of two common urgent general surgery situations, appendicitis and cholecystitis, during the COVID-19 outbreak in a region with a high incidence of COVID. METHODS: Retrospective analysis of all appendicitis and cholecystitis cases in a region of western Switzerland (population 850,000) during the first pandemic peak. Primary endpoints were delay after first symptoms to consultation and delay to surgery. Secondary endpoints were disease severity and postoperative outcome compared with the same period in 2019. RESULTS: 214 patients were included: 99 during the 2020 pandemic and 115 in 2019. Median time to consultation for appendicitis was 48 hours (interquartile range [IQR] 24–96) in 2020 and 24 hours (12–36) in 2019 (p = 0.004); for cholecystitis, it was 48 hours (24–96) in 2020 and 36 hours (24–72) in 2019 (p = 0.28). Median time to surgery after consultation for appendicitis was 6.5 hours (IQR 4–18) in 2020 and 7.3 hours (5–9) in 2019 (p = 0.68), for cholecystitis 20 hours (12–48) in 2020 and 23 hours (14–39) in 2019 (p = 0.91). More antibiotics were prescribed after appendectomy in 2020 (46 vs 31%, p = 0.026). Significantly more perforations/abscesses related to appendicitis and cholecystitis were observed in 2020 during the COVID-19 outbreak (p = 0.007 and p = 0.044, respectively). No differences were found for postoperative complications and length of stay. CONCLUSIONS: A delay in patients’ arrival at the emergency room was observed for appendicitis. No delay to surgery during the pandemic was observed. A higher rate of perforations and abscesses associated with appendicitis and cholecystitis was observed during the pandemic period. Morbidity and reoperation rate did not change.

SUMMARY Immune checkpoint blockade (ICB) has improved outcomes in some cancers. A major limitation of ICB is that most patients fail to respond, which is partly attributable to immunosuppression. Obesity appears to improve immune checkpoint therapies in some cancers, but impacts on breast cancer (BC) remain unknown. In lean and obese mice, tumor progression and immune reprogramming were quantified in BC tumors treated with anti-programmed death-1 (PD-1) or control. Obesity augments tumor incidence and progression. Anti-PD-1 induces regression in lean mice and potently abrogates progression in obese mice. BC primes systemic immunity to be highly responsive to obesity, leading to greater immunosuppression, which may explain greater anti-PD-1 efficacy. Anti-PD-1 significantly reinvigorates antitumor immunity despite persistent obesity. Laminin subunit beta-2 (Lamb2), downregulated by anti-PD-1, significantly predicts patient survival. Lastly, a microbial signature associated with anti-PD-1 efficacy is identified. Thus, anti-PD-1 is highly efficacious in obese mice by reinvigorating durable antitumor immunity., In brief Pingili et al. show that breast cancer exacerbates obesity-driven immunosuppression. Anti-PD-1 reinvigorates antitumor immunity in the tumor microenvironment, mammary fat pad, and peripherally. Lamb2, downregulated by anti-PD-1 in tumors, associates with obesity and poor survival in patients. A microbial signature associated with immune checkpoint inhibitor efficacy is identified., Graphical Abstract

The Si channel of advanced p-type transistors has been replaced by a compressively strained Silicon-Germanium channel (SiGe) in order to improve the device performances. The SiGe thickness and composition must be precisely controlled to reproducibly obtain the same characteristics. In this study, the benefits of X-ray Photoelectron Spectroscopy (XPS) for the process development and the industrial control of thin SiGe channel layers are shown. The use of a parallel Angle Resolved XPS (pARXPS) allowed us to obtain the germanium distribution in very thin SiGe channels, a useful information to better understand the impact of various process steps on the germanium distribution. The hybridization of in-line XPS and X-Ray Reflectivity (XRR) has been used as an industrial process control characterization method to jointly determine the SiGe channel's thickness and germanium composition. This hybrid industrial metrology technique has shown promising results.

Very few published studies have examined the outcomes of postgraduate scholarship programs. Basing our analysis on these studies and on internal reports from U.S. and Canadian organizations involved in scholarship programs, we have compiled an overview of the wide variety of indicators and methods that have been used, and conducted a comparative study of outcomes using the four most commonly used indicators: awarded diploma, obtained job, obtained related job, and pursuing studies. Our analysis revealed several methodological pitfalls in comparing the results. Although the use of available data limits the depth of a comparative analysis, our results show that scholarship programs tend to increase the rate of awarded diplomas.

Obesity is an emerging global epidemic with profound challenges to world health care economies and societies. Traditional approaches to fighting obesity have not shown promise in promoting a decline in obesity prevalence. The gut microbiota is becoming widely appreciated for its role in regulating metabolism and thus represents a target for new therapies to combat obesity and associated comorbidities. This article provides an overview of altered microbial community structure in obesity, dietary impact on the gut microbiota, host-microbe interactions contributing to the disease, and improvements in microbial assemblage after bariatric surgery and with therapies targeting the gut microbiome.

Airway microbial dysbiosis is associated with subsequent bronchopulmonary dysplasia (BPD) development in very preterm infants. However, the relationship of airway microbiome in normal pulmonary development has not been defined. To better understand the role of the airway microbiome, we compared normal and abnormal alveolar and pulmonary vascular development in mice with or without a microbiome. We hypothesized that the lungs of germ-free (GF) mice would have an exaggerated phenotypic response to hyperoxia compared with non–germ-free (NGF) mice. With the use of a novel gnotobiotic hyperoxia chamber, GF and NGF mice were exposed to either normoxia or hyperoxia. Alveolar morphometry, pulmonary mechanics, echocardiograms, inflammatory markers, and measures of pulmonary hypertension were studied. GF and NGF mice in normoxia showed no difference, whereas GF mice in hyperoxia showed protected lung structure and mechanics and decreased markers of inflammation compared with NGF mice. We speculate that an increase in abundance of pathogenic bacteria in NGF mice may play a role in BPD pathogenesis by regulating the proinflammatory signaling and neutrophilic inflammation in lungs. Manipulation of the airway microbiome may be a potential therapeutic intervention in BPD and other lung diseases.

During the newborn period, intestinal commensal bacteria influence pulmonary mucosal immunology via the gut-lung axis. Epidemiological studies have linked perinatal antibiotic exposure in human newborns to an increased risk for bronchopulmonary dysplasia, but whether this effect is mediated by the gut-lung axis is unknown. To explore antibiotic disruption of the newborn gut-lung axis, we studied how perinatal maternal antibiotic exposure influenced lung injury in a hyperoxia-based mouse model of bronchopulmonary dysplasia. We report that disruption of intestinal commensal colonization during the perinatal period promotes a more severe bronchopulmonary dysplasia phenotype characterized by increased mortality and pulmonary fibrosis. Mechanistically, metagenomic shifts were associated with decreased IL-22 expression in bronchoalveolar lavage and were independent of hyperoxia-induced inflammasome activation. Collectively, these results demonstrate a previously unrecognized influence of the gut-lung axis during the development of neonatal lung injury, which could be leveraged to ameliorate the most severe and persistent pulmonary complication of preterm birth.