Dying for Oxygen: Roles of Hypoxia Inducible Factor 2a and 3a during lung development

Congenital lung lesions comprise a broad spectrum of rare but clinically significant developmental abnormalities, including congenital cystic adenomatoid malformation, bronchopulmonary sequestrations, congenital lobar emphysema, and bronchogenic cysts, which are commonly surgically treated. Although the terms congenital cystic adenomatoid malformation, bronchopulmonary sequestrations, congenital lobar emphysema, and bronchogenic cysts are entrenched in clinical usage and comfortably correspond to rigid pathologic definitions, there is a considerable overlap in the findings. Disregarding the controversy about lesion nomenclature and classification, it is widely accepted that congenital lung lesions result from perturbations in lung and airway embryogenesis. It is generally accepted that both place (level in the tracheobronchial tree) and timing (gestational age) of the embryologic insult correlates with the type of lesion and histopathology that is manifested. The objective of this review is to briefly review normal lung development and to analyze the known molecular mechanisms underlying those diseases

TANGO: Time-Reversal Latent GraphODE for Multi-Agent Dynamical Systems

Learning complex multi-agent system dynamics from data is crucial across many domains, such as in physical simulations and material modeling. Extended from purely data-driven approaches, existing physics-informed approaches such as Hamiltonian Neural Network strictly follow energy conservation law to introduce inductive bias, making their learning more sample efficiently. However, many real-world systems do not strictly conserve energy, such as spring systems with frictions. Recognizing this, we turn our attention to a broader physical principle: Time-Reversal Symmetry, which depicts that the dynamics of a system shall remain invariant when traversed back over time. It still helps to preserve energies for conservative systems and in the meanwhile, serves as a strong inductive bias for non-conservative, reversible systems. To inject such inductive bias, in this paper, we propose a simple-yet-effective self-supervised regularization term as a soft constraint that aligns the forward and backward trajectories predicted by a continuous graph neural network-based ordinary differential equation (GraphODE). It effectively imposes time-reversal symmetry to enable more accurate model predictions across a wider range of dynamical systems under classical mechanics. In addition, we further provide theoretical analysis to show that our regularization essentially minimizes higher-order Taylor expansion terms during the ODE integration steps, which enables our model to be more noise-tolerant and even applicable to irreversible systems. Experimental results on a variety of physical systems demonstrate the effectiveness of our proposed method. Particularly, it achieves an MSE improvement of 11.5 % on a challenging chaotic triple-pendulum systems

Application of extracorporeal membrane oxygenation to adults with cardiogenic shock and cardiac arrest in hospital

Objective·To assess the effect of veno-arterial extracorporeal membrane oxygenation (VA-ECMO) treatment on the mortality rate of patients suffering from cardiogenic shock and cardiac arrest in hospital.Methods·A total of 19 patients with cardiogenic shock or cardiac arrest who were treated with VA-ECMO treatment in Suzhou Kowloon Hospital, Shanghai Jiao Tong University School of Medicine from September 2017 to March 2022 were included in the retrospective study. Patients were divided into extracorporeal cardiopulmonary resuscitation (ECPR) group (n=9) and VA-ECMO for cardiogenic shock (E-CS) group (n=10) according to whether cardiac arrest had occurred. The general demographic data, clinical data, Sequential Organ Failure Assessment (SOFA) scores, postoperative complications and prognostic indicators of the two groups of patients were collected. Univariate and multivariate Cox proportional hazard regression analyses were used to evaluate the correlation between each covariate and hospital mortality.Results·Among the included patients, there were 15 males (78.9%), with an average age of 46.5 (34.5, 61.6) years. The incidence of postoperative complications was as follows: bleeding (47.4%), AKI (36.8%), infection (31.6%), limb ischemia (15.8%) and cerebrovascular accident (5.3%). The duration of VA-ECMO was 4.0 (2.0, 6.8) days, and the intensive care duration was 11.5 (5.8, 26.2) days; the ECMO withdrawal success rate was 63.2%, and the hospital mortality was 63.2%. The results of univariate Cox proportional hazard regression analysis showed that AKI (prior to VA-ECMO initiation), postoperative complications of infection and limb ischemia were correlated with the hospital mortality of patients (all P<0.05). The results of multivariate Cox proportional hazard regression analysis showed that AKI (prior to VA-ECMO initiation), postoperative complications of infection and limb ischemia were also independent risk factors for the hospital mortality of patients (all P<0.05).Conclusion·For patients with cardiogenic shock and cardiac arrest treated with VA-ECMO, AKI (prior to VA-ECMO initiation), postoperative infection and limb ischemia are independently associated with higher hospital mortality

Serotonin and corticosterone rhythms in mice exposed to cigarette smoke and in patients with COPD:implication for COPD-associated neuropathogenesis

The circadian timing system controls daily rhythms of physiology and behavior, and disruption of clock function can trigger stressful life events. Daily exposure to cigarette smoke (CS) can lead to alteration in diverse biological and physiological processes. Smoking is associated with mood disorders, including depression and anxiety. Patients with chronic obstructive pulmonary disease (COPD) have abnormal circadian rhythms, reflected by daily changes in respiratory symptoms and lung function. Corticosterone (CORT) is an adrenal steroid that plays a considerable role in stress and anti-inflammatory responses. Serotonin (5-hydroxytryptamine; 5HT) is a neurohormone, which plays a role in sleep/wake regulation and affective disorders. Secretion of stress hormones (CORT and 5HT) is under the control of the circadian clock in the suprachiasmatic nucleus. Since smoking is a contributing factor in the development of COPD, we hypothesize that CS can affect circadian rhythms of CORT and 5HT secretion leading to sleep and mood disorders in smokers and patients with COPD. We measured the daily rhythms of plasma CORT and 5HT in mice following acute (3 d), sub-chronic (10 d) or chronic (6 mo) CS exposure and in plasma from non-smokers, smokers and patients with COPD. Acute and chronic CS exposure affected both the timing (peak phase) and amplitude of the daily rhythm of plasma CORT and 5HT in mice. Acute CS appeared to have subtle time-dependent effects on CORT levels but more pronounced effects on 5HT. As compared with CORT, plasma 5HT was slightly elevated in smokers but was reduced in patients with COPD. Thus, the effects of CS on plasma 5HT were consistent between mice and patients with COPD. Together, these data reveal a significant impact of CS exposure on rhythms of stress hormone secretion and subsequent detrimental effects on cognitive function, depression-like behavior, mood/anxiety and sleep quality in smokers and patients with COPD

Multimodal Single-Cell/Nucleus RNA Sequencing Data Analysis Uncovers Molecular Networks Between Disease-Associated Microglia and Astrocytes With Implications for Drug Repurposing in Alzheimer’s Disease

Because disease-associated microglia (DAM) and disease-associated astrocytes (DAA) are involved in the pathophysiology of Alzheimer\u27s disease (AD), we systematically identified molecular networks between DAM and DAA to uncover novel therapeutic targets for AD. Specifically, we develop a network-based methodology that leverages single-cell/nucleus RNA sequencing data from both transgenic mouse models and AD patient brains, as well as drug-target network, metaboliteenzyme associations, the human protein-protein interactome, and large-scale longitudinal patient data. Through this approach, we find both common and unique gene network regulators between DAM (i.e., PAK1, MAPK14, and CSF1R) and DAA (i.e., NFKB1, FOS, and JUN) that are significantly enriched by neuro-inflammatory pathways and well-known genetic variants (i.e., BIN1). We identify shared immune pathways between DAM and DAA, including Th17 cell differentiation and chemokine signaling. Last, integrative metabolite-enzyme network analyses suggest that fatty acids and amino acids may trigger molecular alterations in DAM and DAA. Combining network-based prediction and retrospective case-control observations with 7.2 million individuals, we identify that usage of fluticasone (an approved glucocorticoid receptor agonist) is significantly associated with a reduced incidence of AD (hazard ratio [HR] = 0.86, 95% confidence interval [CI] 0.83-0.89, P \u3c 1.0 × 10 - 8). Propensity score-stratified cohort studies reveal that usage of mometasone (a stronger glucocorticoid receptor agonist) is significantly associated with a decreased risk of AD (HR = 0.74, 95% CI 0.68-0.81, P \u3c 1.0 × 10 - 8) compared to fluticasone after adjusting age, gender, and disease comorbidities. In summary, we present a network-based, multimodal methodology for single-cell/nucleus genomics-informed drug discovery and have identified fluticasone and mometasone as potential treatments in AD

Cluster-Like Headache Secondary to Anamnesis of Sphenoid Ridge Meningioma: A Case Report and Literature Review

Cluster headache is generally considered to be a primary headache; secondary cluster-like headache is quite rare, while cluster-like headache secondary to meningioma is even rarer. Here, we describe an unusual case with cluster-like headache 2.5 years after sphenoid ridge meningioma surgery. The cluster-like headache and meningioma were on the same side, and even at the same position. Furthermore, the cluster-like headache lasted for 6 months. In addition, the patient did not respond well to conventional treatments for cluster headache, such as oxygen inhalation, carbamazepine, and tramadol. Brain magnetic resonance imaging demonstrated a softening lesion, glial hyperplasia, and localized thickening and enhancement of the dura in the left frontal-temporal lobe. However, positron-emission computed tomography showed reduced metabolism in the left frontal-temporal lobe. Although the possibility of a primary headache cannot be completely eliminated, the association between cluster-like headache and probable tumor recurrence or postoperative changes should be considered

Hyperbaric oxygen therapy for late radiation-induced tissue toxicity: Prospectively patient-reported outcome measures in breast cancer patients

__Introduction:__ This study examines patient reported outcome measures of women undergoing hyperbaric oxygen treatment (HBOT) after breast-conserving therapy. __Method:__ Included were 57 women treated with HBOT for late radiation-induced tissue toxicity (LRITT) referred in the period January 2014-December 2015. HBOT consisted of (on average) 47 sessions. In total, 80 min of 100 % O2 was administered under increased pressure of 2.4 ATA. Quality of life was assessed before and after treatment using the European Organization for Research and Treatment of Cancer (EORTC) QLQ-BR23, and a NRS pain score. __Results:__ Fifty-seven women were available for evaluation before and after treatment. Before HBOT, patients had severe complaints of pain in the arm/shoulder (46 %), swollen arm/hand (14 %), difficulty to raise arm or move it sideways (45 %), pain in the area of the affected breast (67 %), swollen area of the affected breast (45 %), oversensitivity of the affected breast (54 %), and skin problems on/in the area of the affected breast (32 %); post HBOT, severe complaints were still experienced in 17, 7, 22, 15, 13, 15, and 11 % of the women, respectively. Differences were all significant. The NRS pain score improved at least 1 point (range 0-10) in 81 % of the patients (p < 0.05). __Conclusion:__ In these breast cancer patients treated with HBOT for LRITT, the patient-reported outcomes were positive and improvements were observed. HBOT was a well-tolerated treatment for LRITT and its side-effects were both minimal and reversible

Evidence for e+e−→γχc1,2e^+e^-\to\gamma\chi_{c1, 2} at center-of-mass energies from 4.009 to 4.360 GeV

Using data samples collected at center-of-mass energies of $\sqrt{s}$ = 4.009, 4.230, 4.260, and 4.360 GeV with the BESIII detector operating at the BEPCII collider, we perform a search for the process $e^+e^-\to\gamma\chi_{cJ}$ $(J = 0, 1, 2)$ and find evidence for $e^+e^-\to\gamma\chi_{c1}$ and $e^+e^-\to\gamma\chi_{c2}$ with statistical significances of 3.0$\sigma$ and 3.4$\sigma$, respectively. The Born cross sections $\sigma^{B}(e^+e^-\to\gamma\chi_{cJ})$, as well as their upper limits at the 90% confidence level are determined at each center-of-mass energy.Comment: 8 pages, 7 figures, 3 table