Miracle-dz/UniFAR-FTUs huggingface dataset:
Environmental effects on the genetic architecture of fitness components in a simultaneous hermaphrodite.

Understanding how environmental change affects genetic variances and covariances of reproductive traits is key to formulate firm predictions on evolutionary responses. This is particularly true for sex-specific variance in reproductive success, which has been argued to affect how populations can adapt to environmental change. Our current knowledge on the impact of environmental stress on sex-specific genetic architecture of fitness components is still limited and restricted to separate-sexed organisms. However, hermaphroditism is widespread across animals and may entail interesting peculiarities with respect to genetic constraints imposed on the evolution of male and female reproduction. We explored how food restriction affects the genetic variance-covariance (G) matrix of body size and reproductive success of the simultaneously hermaphroditic freshwater snail Physa acuta. Our results provide strong evidence that the imposed environmental stress elevated the opportunity for selection in both sex functions. However, the G matrix remained largely stable across the tested food treatments. Importantly, our results provide no support for cross-sex genetic correlations suggesting no strong evolutionary coupling of male and female reproductive traits. We discuss potential implications for the adaptation to changing environments and highlight the need for more quantitative genetic studies on male and female fitness components in simultaneous hermaphrodites.
Narrative Vs. Standard of Care Messages: Testing How Communication Can Positively Influence Adolescents with Type 1 Diabetes

Adolescents with type 1 diabetes (T1D) face a variety of challenges in disease management, and many struggle to achieve optimal glycemic control. Health communication through didactic messaging about the importance of self-management is a commonly used strategy for this population, but narratives have been underutilized. The purpose of this study was to determine if narratives would provide a better tool to improve disease management for adolescents overcoming T1D-specific issues. Adolescent ages 12–17 (N = 191) were enrolled in an online experiment and viewed sets of narratives or standard of care messages. Outcomes were broken into three categories: message evaluation, specifically perceived message effectiveness (PME), and positive emotional reactions; beliefs such as self-efficacy, outcome expectations, and stress and burnout perceptions, and behaviors including disease management and interpersonal communication. Narratives did not significantly outperform standard of care messages, but both message types scored high on PME and other outcomes. We conclude that both narrative and didactic formats may offer utility for healthcare providers working with adolescents, in that narratives provide stories that may inspire positive emotions while standard of care messages provide the necessary clinical information needed to set goals for self-management.
Comparison of pyrotinib or lapatinib with chemotherapy for patients with HER2 positive breast cancer after first-line treatment failure: a retrospective study.

OBJECTIVE To explore the difference in efficacy and safety of pyrotinib or lapatinib combined with chemotherapy in human epidermal growth factor receptor-2 (HER-2) positive breast cancer patients who failed the first-line trastuzumab-containing treatment. METHODS The present retrospective study included 164 HER-2 positive breast cancer patients admitted to our hospital. Among them, 68 cases received pyrotinib combined with chemotherapy after the failure of trastuzumab first-line treatment (pyrotinib group), and the other 96 cases received lapatinib combined chemotherapy (lapatinib group). The end of the follow-up time was set as June 1, 2020. The primary endpoint was progression free survival (PFS), and the secondary endpoints included best objective response rate (ORR) and safety. RESULTS Till the end of the follow-up, the best ORR (60.3% vs. 34.4%) in the pyrotinib group was significantly higher than that in the lapatinib group, and the median PFS (9.0 months vs. 6.2 months) was also largely prolonged (P<0.01). In addition, the median PFS of the patients with brain metastases in the pyrotinib group was 6.5 months, and was much longer that in the lapatinib group which wereth 3.5 months in length (P<0.05). Multivariate COX regression analysis showed that pyrotinib combined with chemotherapy (HR=0.653, P<0.05) was associated with longer PFS of patients, while the lapatinib group had a higher proportion of vomiting and hand foot syndrome than the pyrotinib group (P<0.05). CONCLUSION After the failure of first-line trastuzumab-containing treatment, combination of pyrotinib with chemotherapy has more significant short-term efficacy in HER-2 positive breast cancer patients than lapatinib combined with chemotherapy, especially in patients with brain metastasis.
The roles of the glucagon-like peptide-2 and the serum TGF-β1 levels in the intestinal barrier and immune functions in rats with obstructive jaundice.

OBJECTIVE To determine the mechanisms by which glucagon-like peptide-2 (GLP-2) impacts the intestinal barrier function, the immune function, and the serum transforming growth factor-β1 (TGF-β1) levels in rats with obstructive jaundice. METHODS Overall, 72 SPF-grade healthy Wistar rats were randomly divided into 4 groups containing 18 rats each: the observation group (ligation of common bile duct, intraperitoneal GLP-2 injection), the control group (ligation of common bile duct, normal saline), the sham-operated group (common bile duct exposed without ligation, normal saline), and the blank group. The serum immune function and the TGF-β1 levels were measured on days 3, 7, and 14 after the intervention. RESULTS The body mass was determined to be significantly less in the control group than in the other three groups on day 14 after the intervention (P < 0.05). The TGF-β1, endotoxin, alanine aminotransferase (ALT), and bilirubin were expressed at significantly higher levels in the control group compared with the blank and sham-operated groups and were the highest at each time point, but the levels in the observation group were significantly decreased after the intervention (P < 0.05). CONCLUSIONS We found that GLP-2 can decrease the serum TGF-β1 levels, regulate the immune function, reduce the endotoxin and bilirubin, and protect the intestinal barrier function in rats with obstructive jaundice.
Computed tomography to identify risk factors for left circumflex artery injury during mitral surgery.

OBJECTIVES Cases in which the left circumflex coronary artery (LCX) runs close to the mitral annulus are considered high risk for LCX injury during mitral surgery. We investigated the anatomical relationship between the LCX and the mitral annulus using 3-dimensional (3D) computed tomography (CT). METHODS We constructed 3D-CT images of the LCX and the mitral annulus before surgery in 122 patients with mitral regurgitation (MR). We classified coronary dominance by 3D-CT and MR aetiologies (degenerative, atrial functional MR, ventricular functional MR and Barlow's disease) using echocardiography. We detected the point on the mitral annulus closest to the LCX (X point) and measured the minimum distance from the LCX to the mitral annulus (mCAD). We judged whether atrioventricular disjunction existed using CT. We also investigated the factors affecting mCAD and examined how coronary dominance and MR aetiologies relate to the location of the X point. RESULTS The median mCAD was 4.2 mm (range 0.9-11.4 mm). Considering coronary dominance and MR aetiologies, mCAD was shorter in patients with left coronary dominance and Barlow's disease. The X point mostly existed on the lateral side of the posterior annulus, but it sometimes existed on the medial side. Multiple regression revealed left dominance and mitral annular disjunction as significant factors affecting mCAD (P = 0.01). CONCLUSIONS The anatomical relationship between the LCX and the mitral annulus can be recognized using superimposed 3D-CT images. This approach is useful to avoid LCX injury in mitral valve surgery since the X point varies between patients.
ERS clinical practice guidelines: high-flow nasal cannula in acute respiratory failure

Background High-flow nasal cannula (HFNC) has become a frequently used noninvasive form of respiratory support in acute settings; however, evidence supporting its use has only recently emerged. These guidelines provide evidence-based recommendations for the use of HFNC alongside other noninvasive forms of respiratory support in adults with acute respiratory failure (ARF). Materials and methodology The European Respiratory Society task force panel included expert clinicians and methodologists in pulmonology and intensive care medicine. The task force used the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) methods to summarise evidence and develop clinical recommendations for the use of HFNC alongside conventional oxygen therapy (COT) and noninvasive ventilation (NIV) for the management of adults in acute settings with ARF. Results The task force developed eight conditional recommendations, suggesting the use of 1) HFNC over COT in hypoxaemic ARF; 2) HFNC over NIV in hypoxaemic ARF; 3) HFNC over COT during breaks from NIV; 4) either HFNC or COT in post-operative patients at low risk of pulmonary complications; 5) either HFNC or NIV in post-operative patients at high risk of pulmonary complications; 6) HFNC over COT in nonsurgical patients at low risk of extubation failure; 7) NIV over HFNC for patients at high risk of extubation failure unless there are relative or absolute contraindications to NIV; and 8) trialling NIV prior to use of HFNC in patients with COPD and hypercapnic ARF. Conclusions HFNC is a valuable intervention in adults with ARF. These conditional recommendations can assist clinicians in choosing the most appropriate form of noninvasive respiratory support to provide to patients in different acute settings. This guideline provides evidence-based recommendations for the use of high-flow nasal cannula alongside other noninvasive forms of respiratory support in adults with acute respiratory failure https://bit.ly/3mgwO8h
Lung epithelial and endothelial damage, loss of tissue repair, inhibition of fibrinolysis, and cellular senescence in fatal COVID-19

Description Lung epithelial and endothelial cell damage and defective lung tissue repair contribute to fatal COVID-19. A window into lung injury in COVID-19 In new work, D’Agnillo et al. perform a systems biology analysis of lung autopsy samples from 18 patients with fatal COVID-19. They report that damage to the cells lining lung branches and blood vessel injury together with defective lung tissue repair after SARS-CoV-2 infection resulted in a fatal outcome. These findings further define the molecular features underlying the lung’s response to SARS-CoV-2 infection and indicate stages of disease progression that may help to guide development of therapies to treat patients with severe COVID-19. Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is characterized by respiratory distress, multiorgan dysfunction, and, in some cases, death. The pathological mechanisms underlying COVID-19 respiratory distress and the interplay with aggravating risk factors have not been fully defined. Lung autopsy samples from 18 patients with fatal COVID-19, with symptom onset-to-death times ranging from 3 to 47 days, and antemortem plasma samples from 6 of these cases were evaluated using deep sequencing of SARS-CoV-2 RNA, multiplex plasma protein measurements, and pulmonary gene expression and imaging analyses. Prominent histopathological features in this case series included progressive diffuse alveolar damage with excessive thrombosis and late-onset pulmonary tissue and vascular remodeling. Acute damage at the alveolar-capillary barrier was characterized by the loss of surfactant protein expression with injury to alveolar epithelial cells, endothelial cells, respiratory epithelial basal cells, and defective tissue repair processes. Other key findings included impaired clot fibrinolysis with increased concentrations of plasma and lung plasminogen activator inhibitor-1 and modulation of cellular senescence markers, including p21 and sirtuin-1, in both lung epithelial and endothelial cells. Together, these findings further define the molecular pathological features underlying the pulmonary response to SARS-CoV-2 infection and provide important insights into signaling pathways that may be amenable to therapeutic intervention.
Secondary hypoxic ischemia alters neurobehavioral outcomes, neuroinflammation, and oxidative stress in mice exposed to controlled cortical impact

Objective Hypoxic ischemia (HI) is a secondary insult that can cause fatal neurologic outcomes after traumatic brain injury (TBI), ranging from mild cognitive deficits to persistent vegetative states. We here aimed to unravel the underlying pathological mechanisms of HI injury in a TBI mouse model. Methods Neurobehavior, neuroinflammation, and oxidative stress were assessed in a mouse model of controlled cortical impact (CCI) injury followed by HI. Mice underwent CCI alone, CCI followed by HI, HI alone, or sham operation. HI was induced by one-vessel carotid ligation with 1 hour of 8% oxygen in nitrogen. Learning and memory were assessed using the novel object recognition test, contextual and cued fear conditioning, and Barnes maze test. Brain cytokine production and oxidative stress-related components were measured. Results Compared to TBI-only animals, TBI followed by HI mice exhibited significantly poorer survival and health scores, spatial learning and memory in the Barnes maze test, discrimination memory in the novel object recognition test, and fear memory following contextual and cued fear conditioning. Malondialdehyde levels were significantly lower, whereas glutathione peroxidase activity was significantly higher in TBI followed by HI mice compared to TBI-only and sham counterparts, respectively. Interleukin-6 levels were significantly higher in TBI followed by HI mice compared to both TBI-only and sham animals. Conclusion Post-traumatic HI aggravated deficits in spatial, fear, and discrimination memory in an experimental TBI mouse model. Our results suggest that increased neuroinflammation and oxidative stress contribute to HI-induced neurobehavioral impairments after TBI.
Ophthalmological Findings in Patients with SARS-CoV-2 Infection Examined at the National Institute of Infectious Diseases - INI/Fiocruz

ABSTRACT Purpose To describe the clinical characteristics, severity, and ophthalmological changes in SARS-CoV-2 patients through ophthalmological examinations performed at the reference center of the National Institute of Infectious Diseases, Brazil. Methods This cross-sectional study assessed the examination results of SARS-CoV-2 patients from July 2020 to November 2020. In total, 150 patients were included and allocated into three groups of 50 patients depending on the disease severity. Group 1 patients were in the intensive care unit (ICU), group 2 patients were in the semi-ICU, and group 3 patients were outpatients. Results Ten (6.7%) patients exhibited ophthalmological changes; five (10%), four (8%), and one (2%) patients in groups 1, 2, and 3, respectively. Ophthalmological findings included candle flame hemorrhage and cotton wool exudates. We analyzed the general characteristics of the 10 patients with ophthalmological changes. Nine were hospitalized and one was seen on an outpatient basis. Conclusion We observed ophthalmic changes in patients with SARS-CoV-2 infection, despite the absence of any clinical or laboratory risk factors indicative of such changes.
Molecular characterization of the aryl hydrocarbon receptor 2 gene in black rockfish, Sebastes schlegelii, and its expression patterns upon exposure to benzo[a]pyrene, 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin, and β‐naphthoflavone

The aryl hydrocarbon receptor (AhR) is a ligand‐activated transcription factor that mediates the toxicity of halogenated and polycyclic aromatic hydrocarbons in vertebrates. Thus, increased knowledge of AhR‐mediated responses to xenobiotics is imperative. Sebastes schlegelii is increasingly being used as a model for studying environmental toxicology; hence, in this study, the presence of AhR2 was evaluated in S. schlegelii. The results showed that the predicted AhR2 amino acid sequence contained regions characteristic of other vertebrate AhRs, including the basic helix–loop–helix and PER–ARNT–SIM domains in the N‐terminal half, but it had minor similarity with other vertebrate AhRs across the C‐terminal half; it did not contain the distinct glutamine‐rich domains found in mammalian AhR2. Phylogenetic analysis demonstrated that S. schlegelii AhR2 was clustered within the teleost AhR2 branch. Additionally, AhR2 mRNA was detectable in all 11 tissues tested, with the highest mRNA levels in the heart, pyloric ceca, and liver. Furthermore, exposure to the AhR agonists showed that 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin (TCDD, 1 μg/g body weight) induced a significantly higher increases in AhR2 expression in the gills, liver, kidneys, and spleen in 48 h than benzo[a]pyrene (2 μg/g body weight), and β‐naphthoflavone (50‐μg/g body weight); AhR2 mRNA levels upon TCDD exposure were up‐regulated by 16‐ and 10‐fold in the gills and liver, respectively. These findings indicated that AhR was a highly sensitive receptor against TCDD. Thus, investigating AhR2 expression in the presence of other xenobiotics might offer further information for the elucidation of its crucial role in mediating toxicant metabolism in S. schlegelii.
Serum cadmium positively correlates with inflammatory cytokines in patients with chronic obstructive pulmonary disease

Cadmium is a ubiquitous toxic heavy metal and environmental toxicant. Inflammation exerts central roles in the process of chronic obstructive pulmonary disease (COPD). However, few epidemiological studies on the correlation between cadmium exposure and COPD are available. The aim of this study was to evaluate the correlations among serum cadmium, inflammatory cytokines and pulmonary function in COPD patients.
Metabolomic differences in lung function metrics: evidence from two cohorts

Rationale The biochemical mechanisms underlying lung function are incompletely understood. Objectives To identify and validate the plasma metabolome of lung function using two independent adult cohorts: discovery—the European Prospective Investigation into Cancer–Norfolk (EPIC-Norfolk, n=10 460) and validation—the VA Normative Aging Study (NAS) metabolomic cohort (n=437). Methods We ran linear regression models for 693 metabolites to identify associations with forced expiratory volume in one second (FEV1) and the ratio of FEV1 to forced vital capacity (FEV1/FVC), in EPIC-Norfolk then validated significant findings in NAS. Significance in EPIC-Norfolk was denoted using an effective number of tests threshold of 95%; a metabolite was considered validated in NAS if the direction of effect was consistent and p<0.05. Measurements and main results Of 156 metabolites that associated with FEV1 in EPIC-Norfolk after adjustment for age, sex, body mass index, height, smoking and asthma status, 34 (21.8%) validated in NAS, including several metabolites involved in oxidative stress. When restricting the discovery sample to men only, a similar percentage, 18 of 79 significant metabolites (22.8%) were validated. A smaller number of metabolites were validated for FEV1/FVC, 6 of 65 (9.2%) when including all EPIC-Norfolk as the discovery population, and 2 of 34 (5.9%) when restricting to men. These metabolites were characterised by involvement in respiratory track secretants. Interestingly, no metabolites were validated for both FEV1 and FEV1/FVC. Conclusions The validation of metabolites associated with respiratory function can help to better understand mechanisms of lung health and may assist the development of biomarkers.
Effects of Primary Tumor Resection on Metastatic Breast Cancer Survival and the Predictive Power of Neutrophil: Lymphocyte Ratio on Prognosis.

Objective The aim was to investigate the effect of primary tumor resection (PTR) on survival in metastatic breast cancer patients and to assess the power of the neutrophil-to-lymphocyte ratio (NLR) regarding the prediction of prognosis in this patient group. Materials and Methods Female patients diagnosed with and starting treatment for metastatic breast cancer from 2003 to 2016 in the general surgery and oncology clinics at a single center were retrospectively reviewed. Pre-treatment NLR value and survival situations were evaluated. Results A total of 117 patients were enrolled. The disease-specific survival (DSS) of the patients was 41.4 months. When stratified into PTR and systemic treatment (ST) groups, there was no difference in the survival (p = 0.054); 43.5 months in the PTR group vs 30.7 months in the ST group. When hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative subgroups were analyzed, DSS was significantly longer (p = 0.02) in the PTR group (55.4 months) compared to the ST group (41.8 months). Finally, in patients with an NLR of <2.3, DSS was significantly longer (p = 0.03) in the PTR group (56.1 months) compared to the ST group (25.2 months). Conclusion These results suggest that DSS can be increased with PTR in selected patients with a diagnosis of metastatic breast cancer. NLR may be useful in selecting patients for appropraite treatment modality.
Regulatory T-cells inhibit microglia-induced pain hypersensitivity in female mice

Peripheral nerve injury-induced neuropathic pain is a chronic and debilitating condition characterized by mechanical hypersensitivity. We previously identified microglial activation via release of colony-stimulating factor 1 (CSF1) from injured sensory neurons as a mechanism contributing to nerve injury-induced pain. Here, we show that intrathecal administration of CSF1, even in the absence of injury, is sufficient to induce pain behavior, but only in male mice. Transcriptional profiling and morphologic analyses after intrathecal CSF1 showed robust immune activation in male but not female microglia. CSF1 also induced marked expansion of lymphocytes within the spinal cord meninges, with preferential expansion of regulatory T-cells (Tregs) in female mice. Consistent with the hypothesis that Tregs actively suppress microglial activation in females, Treg deficient (Foxp3DTR) female mice showed increased CSF1-induced microglial activation and pain hypersensitivity equivalent to males. We conclude that sexual dimorphism in the contribution of microglia to pain results from Treg-mediated suppression of microglial activation and pain hypersensitivity in female mice.