Miracle-dz/UniFAR-FTUs huggingface dataset:
Perioperative Corticosteroid Therapy in Children Undergoing Cardiac Surgery: A Systematic Review and Meta-Analysis

Background: The benefit–risk profile of perioperative corticosteroids in pediatric patients undergoing cardiac surgery remains controversial. Objective: To investigate the influence of perioperative corticosteroids on the postoperative mortality and clinical outcomes in pediatric patients undergoing cardiac surgery with cardiopulmonary bypass. Methods: We conducted a systematic search using MEDLINE, EMBASE, and Cochrane Database through August 31, 2019. We included randomized controlled trials comparing perioperative corticosteroids with other clinical interventions, placebo, or no treatment in children between 0 and 18 years of age undergoing cardiac surgery. The primary outcome of interest was all-cause in-hospital mortality. The secondary outcomes were length of intensive care unit stay (LOIS), duration of mechanical ventilation (DMV), postoperative insulin therapy, postoperative low cardiac output syndrome (LCOS), postoperative infection, maximal temperature (Tmax) in the first 24 h postoperatively, urine output (UO) in the first 24 h postoperatively, serum lactate at postoperative day (POD) 1, blood glucose at POD 1, vasoactive inotrope score (VIS) at POD 1, and postoperative acute kidney injury (AKI). Study quality was assessed using the Cochrane Risk of Bias Assessment Tool. Results: Our analysis included 17 studies and 848 pediatric patients. The data demonstrated that children receiving corticosteroids showed no significant difference on the all-cause in-hospital mortality with a fixed-effect model (RR = 0.59, 95% CI = 0.28–1.25, P = 0.55) compared with controls. For the secondary outcomes, corticosteroids had a statistically significant reduction on the VIS at POD1 (MD = −2.04, 95% CI = −3.96 −0.12, P = 0.04), while it might be significantly associated with an increased blood glucose at POD1 (MD = 1.38, 95% CI = 0.68–2.09, P = 0.0001) and a 2.69-fold higher risk of postoperative insulin therapy (RR = 2.69, 95% CI = 1.37–5.27, P = 0.004). No statistical significance was shown in other secondary outcomes. Conclusion: Perioperative corticosteroids might not significantly improve clinical outcomes identified as mortality, LOIS, DMV, AKI, and LCOS other than VIS at POD1. However, it might increase the blood glucose and episodes of insulin therapy. Perioperative corticosteroids to attenuate the inflammatory response are not supported by available evidence from our study. Further results from ongoing randomized controlled trials with a larger sample size are required.
CBPR Partnerships and Near-Roadway Pollution: A Promising Strategy to Influence the Translation of Research into Practice

Community-based participatory research (CBPR) aims to engage those traditionally left out of the research process. Partnering with community stakeholders to design, plan, implement and disseminate research can facilitate translation into practice. Using qualitative research methods, we set out to explore the policy and practice implications of a CBPR partnership focused on reducing exposure to near-roadway pollution. Key Informant interviews (n = 13) were conducted with individuals from various entities (municipal, state and private) for whom partners to the Community Assessment of Freeway Exposure and Health (CAFEH) provided technical assistance between 2013 and 2017. The findings indicate community research partnerships may have the power to inform local planning efforts. Developers and planners who the partnership consulted indicated a greater awareness of the implications of near-roadway exposure. They also described making changes in their practice based on study findings. The CAFEH partnership has demonstrated active attention to translating knowledge can influence local planning and practice, albeit with some challenges.
Diabetes as a Risk Factor for Abnormal Cognition Development

Background: Diabetes has been shown as a risk factor for cognitive impairments. However, it is still not clear about the time course of developing abnormal cognition in those with diabetes especially if the morbidity accelerates the cognitive deterioration process. Objective: To study how diabetes is related to the abnormal cognition development. Methods: A retrospective analysis was performed using data collected by the National Alzheimer’s Coordinating Center. Incidence, prevalence, and age at onset (AAO) of either mild cognitive impairment (MCI) or dementia were compared between participants with and without diabetes. Results: During a follow-up period of more than 10 years, the diabetic group had a higher incidence and prevalence of MCI or dementia than the non-diabetic group. However, the AAO of either MCI or dementia was independent of the diagnosis of diabetes. Conclusion: Although diabetic patients have a higher incidence and prevalence of abnormal cognition than those without diabetes, diabetes does not accelerate the cognitive deterioration process.
Negative Impact of Sadness on Response Inhibition in Females: An Explicit Emotional Stop Signal Task fMRI Study

Response inhibition is a critical cognitive ability underlying executive control over reactions to external cues, or inner requirements. Previous studies suggest that high arousal negative emotions (e.g., anger or fear) could impair response inhibition in implicit emotional stop signal tasks (eSSTs). However, studies exploring how low arousal negative emotions (e.g., sadness) influence response inhibition remain sparse. In the current study, 20 female college students performed an explicit eSST to explore the influence of sadness on response inhibition and its neural mechanism. Participants are instructed to press a button to sad or neutral facial stimuli while inhibiting their response during the presentation of a stop signal. Results showed that compared with neutral stimuli, sad stimuli were related to increased stop signal reaction time (SSRT) (i.e., worse response inhibition). Compared with neutral condition, higher activation during sad condition was found within the right superior frontal gyrus (SFG), right insula, right middle cingulate cortex (MCC), bilateral superior temporal gyrus (STG), left lingual gyrus, and right motor cortex. These findings indicated that sadness, like other negative emotions, may impair response inhibition in an explicit way and highlight the explicit eSST as a new paradigm to investigate the subtle interaction between negative emotion processing and cognitive control.
Functional neuroimaging of sensorimotor cortices in postmenopausal women with type II diabetes

Abstract. Significance: Deficits in sensorimotor function in persons with type II diabetes mellitus (PwDM) have traditionally been considered a result of peripheral nerve damage. Emerging evidence has suggested that factors outside of nerve damage due to type II diabetes mellitus, such as impaired hemodynamic function, contribute significantly to both sensory and motor deficits in PwDM. Aim: The focus of the current study was to evaluate functional cortical hemodynamic activity during sensory and motor tasks in PwDM. Approach: Functional near-infrared spectroscopy was used to monitor oxyhemoglobin (HbO) and deoxyhemoglobin (HbR) across the cortex during sensory and motor tasks involving the hands. Results: Decline in HbO across sensory and motor regions of interest was found in PwDM with simultaneous deficits in manual motor tasks, providing the first evidence of functional cortical hemodynamic activity deficits relating to motor dysfunction in PwDM. Similar deficits were neither specifically noted in HbR nor during evaluation of sensory function. Health state indices, such as A1c, blood pressure, body mass index, and cholesterol, were found to clarify group effects. Conclusions: Further work is needed to clarify potential sex-based differences in PwDM during motor tasks as well as the root of reduced cortical HbO indices but unchanged HbR indices in PwDM.
Neuronal Transcriptome from C9orf72 Repeat Expanded Human Tissue is Associated with Loss of C9orf72 Function

A hexanucleotide G4C2 repeat expansion in C9orf72 is the most common genetic cause of familial and sporadic cases of amyotrophic lateral sclerosis (ALS) and frontotemporal degeneration (FTD). The mutation is associated with a reduction of C9orf72 protein and accumulation of toxic RNA and dipeptide repeat aggregates. The accumulation of toxic RNA has been proposed to sequester RNA binding proteins thereby altering RNA processing, consistent with previous transcriptome studies that have shown that the C9orf72 repeat expansion is linked to abundant splicing alterations and transcriptome changes. Here, we used a subcellular fractionation method and FACS to enrich for neuronal nuclei from C9orf72 repeat expanded post-mortem human ALS/FTD brains, and to remove neuronal nuclei with TDP-43 pathology which are observed in nearly all symptomatic C9orf72 repeat expanded cases. We show that the C9orf72 expansion is associated with relatively mild gene expression changes. Dysregulated genes were enriched for vesicle transport pathways, which is consistent with the known functions of C9orf72 protein. Further analysis suggests that the C9orf72 transcriptome is not driven by toxic RNA but is rather shaped by the depletion of pathologic TDP-43 nuclei and the loss of C9orf72 expression. These findings argue against RNA binding protein sequestration in neurons as a major contributor to C9orf72 mediated toxicity.
Health Services, Socioeconomic Indicators, and Primary Care Coverage in Mortality by Lower Genital Tract and Breast Neoplasias in Brazilian Women during Reproductive and Non-Reproductive Periods

Women’s health assistance at the low-complexity level is focused on the most common diseases and can be affected by primary health care coverage, particularly in areas far away from large urban centers. Thus, in this work, we aim to analyze the relationship between socioeconomic status, health care indicators, and primary care coverage in mortality from neoplasms of the lower genital tract and breast in Brazilian women during reproductive and non-reproductive periods. We conducted an ecological study at the Gynecology Discipline, Medicine School, University of São Paulo. Secondary data were collected from women according to reproductive periods and mortality data from the Mortality Information System based on International Classification of Disease—10th edition regarding breast and lower genital tract neoplasms in 2017. The health service and socioeconomic indicators were obtained from the Informatics Department of the Unified Health System and Brazilian Institute of Geography and Statistics. Our results showed that primary care coverage and health service indicators were not associated with mortality from breast cancer and the female lower genital tract, both in reproductive and non-reproductive periods. Sociodemographic indicators were found to be associated with mortality from breast cancer and the female lower genital tract, with income being associated with reproductive period (β = −0.4; 95% CI, −0.8 to −0.03) and educational level in the non-reproductive period (β = 9.7; 95% CI, 1.5 to 18.0).
Engaging Patients to Design the Systematic Multi-Domain Alzheimer’s Risk Reduction Trial (SMARRT) Intervention: Findings from a Web-Based Survey

We administered a web-based survey to a convenience sample of 561 patients in a large health system to assess patient attitudes toward dementia prevention in the context of designing a multi-domain Alzheimer’s risk reduction intervention. The majority of respondents reported being very concerned about Alzheimer’s disease, wanted to know their personal risk factors, and were highly motivated to make healthy lifestyle changes to lower dementia risk. The areas they were most interested in targeting to reduce dementia risk included physical activity, cognitive stimulation, nutrition, and sleep. These results provided strong support for our conceptual framework to target higher-risk patients with a personalized risk reduction strategy.
Efficacy and safety of gastric exposed endoscopic full-thickness resection without laparoscopic assistance: a systematic review

Abstract Background and study aims Exposed endoscopic full-thickness resection (Eo-EFTR) without laparoscopic assistance is a minimally invasive natural orifice transluminal endoscopic surgery (NOTES) technique that has shown promising efficacy and safety in resection of gastric submucosal tumors (G-SMTs) arising from muscularis propria (MP). However, data on the efficacy and safety of gastric Eo-EFTR mostly come from relatively small retrospective studies and concern regarding its use still exists. The aim of our systematic review was to assess the efficacy and safety of gastric Eo-EFTR without laparoscopic assistance. Methods A detailed MEDLINE and EMBASE search was performed for papers published from January 1998 to November 2019 and reporting on gastric Eo-EFTR without laparoscopic assistance. The search strategy used the terms “endoscopic full thickness resection” and “gastric” or “stomach”. The primary outcomes were complete resection and surgical conversion rates. The secondary outcomes were overall major adverse events, delayed bleeding, delayed perforation, peritonitis, abdominal abscess and/or abdominal infection and successful Eo-EFTR. Results Fifteen Asian studies were included in our final review, providing data on 750 Eo-EFTR-treated G-SMTs. The per-lesion rate of complete resection and surgical conversion were 98.8 %\0.8 %, respectively. The per-lesion rate of major adverse events, delayed bleeding, delayed perforation and peritonitis, abdominal abscess and/or abdominal infection was 1.6 %\0.5 %\0.1 %\0.9 %, respectively. The per-lesion rate of successful Eo-EFTR (i. e. complete tumor resection and effective endoscopic defect closure) was 98.3 %. Conclusions Eo-EFTR without laparoscopic assistance appears to be highly effective and safe NOTES for removing deep G-SMTs, particularly those arising from MP layer.
Association between Personal Social Capital and Loneliness among Widowed Older People

To explore the association between the personal social capital and loneliness among the widowed older adults in China. Data from 1497 widowed older adults were extracted from China’s Health-Related Quality of Life Survey for Older Adults 2018. The Chinese version of the Personal Social Capital Scale (PSCS-16) was used to evaluate the participants’ status of bonding and bridging social capital (BOC and BRC). Loneliness was assessed by the short-form UCLA Loneliness Scale (ULS-8). Multiple linear regression models were established to examine the relationship between social capital and loneliness. The BOC and BRC of rural widowed older people were significantly lower than those of widowed older people in urban areas, while loneliness of rural widowed older people was higher than that of widowed older people in urban areas. The result of the final model showed that loneliness of rural participants was significantly associated with both BOC (B = 0.141, p = 0.001) and BRC (B = −0.116, p = 0.003). The loneliness of the urban widowed sample had no association with both BOC and BRC (p > 0.05). These findings suggested that more social support and compassionate care should be provided to enrich the personal social capital and thus to reduce loneliness of widowed older adults, especially those in rural areas.
Vaccination Prevented Short-Term Memory Loss, but Deteriorated Long-Term Spatial Memory in Alzheimer’s Disease Mice, Independent of Amyloid-β Pathology

Background: Soluble oligomeric amyloid-β (Aβ), rather than Aβ plaques, seems to be the culprit in Alzheimer’s disease (AD). Accordingly, a new concept vaccine of small cyclic peptide conjugates, selectively targeting oligomeric Aβ, has been developed. Objective: Study the therapeutic potential of this new vaccine in a mouse model for AD. Methods: J20 mice, overexpressing human amyloid precursor protein, were validated for an AD-like phenotype. Then, J20 mice were vaccinated at 2, 3, and 4 months of age and AD phenotype was evaluated at 6, 9, and 12 months of age; or at 9, 10, and 11 months with evaluation at 12 months. Effects on Aβ pathology were studied by plaque load (immunohistochemistry; 6E10) and antibody titers against Aβ (ELISA). AD behavioral phenotype was evaluated by performance in a battery of cognitive tests. Results: J20 mice displayed age-related Aβ plaque development and an AD-like behavioral phenotype. A consistent antibody response to the cyclic peptides was, however, not extended to Aβ, leaving plaque load unaffected. Nevertheless, immunization at young ages prevented working- and short-term spatial memory loss, but deteriorated long-term spatial learning and memory, at 12 months of age. Immunization at later ages did not affect any measured parameter. Conclusion: J20 mice provide a relevant model for AD to study potential anti-Aβ treatment. Early vaccination prevented short-term memory loss at later ages, but deteriorated long-term spatial memory, however without affecting Aβ pathology. Later vaccination had no effects, but optimal timing may require further investigation.
Phosphorylation events surrounding the DNA damage response in "Saccharomyces cerevisiae"

Protein phosphorylation mediated by checkpoint kinases is crucial for the cellular response to DNA damage. The sensor kinases Mec1 and Tel1 initiate the checkpoint signaling cascade by directly activating the checkpoint effector kinase Rad53. This checkpoint pathway, however, is responsive to normal endogenous replication as well. As a result an S-phase specific threshold for Rad53 activation exists, which allows cells to tolerate endogenous damage-like structures. Here we show that Rad53 itself is phosphorylated in a cell-cycle dependent manner independent of DNA damage signaling (Chapter 2). We propose that this is part of the cell-cycle regulated sensitivity of Rad53 to activation. This phosphorylation occurs in G2/M, persists until S phase onset and depends on both the polo-like kinase, Cdc5, and the cyclin-dependent kinase, Cdc28. These cell-cycle dependent phosphorylation events are located in the C-terminal part of Rad53. Serines 774 and 789 were shown to be phosphorylated by mass spectrometry. Mutation of these sites eliminated the cell-cycle dependent phosphorylation of Rad53 and partially impaired the activation of Rad53 in response to minor amounts of DNA damage in G2/M. This led to more rapid checkpoint adaptation in response to irreparable DNA damage. Thus, cell-cycle dependent phosphorylation in the C-terminal part of Rad53 enhances Rad53 activation in response to DNA double strand breaks (DSBs). Mec1 and Tel1 initiate a response to DNA damage independently of Rad53. The phosphorylation of histone H2A at serine 129 (γH2A) at DSBs by Mec1 and Tel1 has an important role in mediating DNA repair. This study shows that the occurrence of γH2A is not limited to DSBs, but also occurs at stalled replication forks (Chapter 3). Using chromatin immunoprecipitation high γH2A levels were monitored at hydroxyurea-stalled replication forks and depended nearly exclusively upon Mec1 kinase activity. Furthermore our study showed that γH2A not only occurs at damaged chromatin but in regions of normally replicating chromatin and near telomeres (Chapter 4). High levels of γH2A could be monitored both in the rDNA of normally growing yeast cells and at telomeres. Here γH2A depended mainly on Tel1 and γH2A levels increased during S phase and during the elongation of critically short telomeres. We also provide evidence that γH2A contributes to telomeric anchoring in S phase yeast cells in addition to the yKu and Sir4 anchoring pathways.
AHNAK2 Is Associated with Poor Prognosis and Cell Migration in Lung Adenocarcinoma

Background Lung adenocarcinoma (LUAD), as the main subtype of lung cancer, is one of the common causes of cancer-related deaths worldwide. The AHNAK family is correlated with cell structure and migration, cardiac calcium channel signaling, and tumor metastasis. Previous studies showed AHNAK2 could promote tumor progression and cell migration in melanoma and renal clear cell carcinoma. However, the role of AHNAK2 in LUAD remains unknown. Methods We examined the levels of AHNAK2 in pathological specimens and the database of Clinical Proteomic Tumor Analysis Consortium-Lung adenocarcinoma (CPTAC-LUAD), The Cancer Genome Atlas-Lung Adenocarcinoma (TCGA-LUAD), Gene Expression Omnibus dataset (GSE72094, GSE26939), and The Genotype-Tissue Expression (GTEx) of lung tissue samples. Univariate Cox regression, multivariate Cox regression, and Kaplan–Meier survival analysis were performed to reveal the relationship between AHNAK2 and prognosis. A nomogram was constructed to predict 2- or 3-year overall survival and validated via calibration curves, receiver operating characteristic (ROC) analysis, and decision curve analysis (DCA). Furthermore, Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were used to explore the functional role of AHNAK2 in lung adenocarcinoma. Finally, by transfecting siRNA, we examined the regulatory effect of AHNAK2 on cell migration. Results The expression of AHNAK2 was upregulated in tumor samples and correlated with poor prognosis in LUAD patients. Nomogram with AHNAK2 and clinical parameters showed a good prediction in overall survival (OS), especially the 2-year OS. In addition, functional analyses and wound healing assay suggested that AHNAK2 might be involved in the regulation of migration in LUAD. Conclusion In summary, our study showed that AHNAK2 might be a novel biomarker in LUAD and revealed the potential mechanism of AHNAK2 in LUAD progression which could provide new insights for target therapy.