Miracle-dz/UniFAR-FTUs huggingface dataset:
Frequency of emergency department visits and hospitalizations due to chronic obstructive pulmonary disease exacerbations in patients included in two models of care

Abstract Introduction: Exacerbations of chronic obstructive pulmonary disease (COPD) have a huge impact on lung function, quality of life and mortality of patients. Emergency Department visits and hospitalizations due to exacerbations cause a significant economic burden on the health system. Objective: To describe the differences in the number of emergency visits and hospitalizations due to exacerbations of COPD among patients included in two models of care of the same institution. Materials and methods: A historical cohort study in which COPD patients who are users of two models of care were included: COPD integrated care program (CICP) and general consultation of pulmonology (GCP). The first model, unlike the second one, offers additional educational activities, 24/7 telephone service, and priority consultations. The number of emergency visits and hospitalizations due to COPD exacerbations in patients who had completed at least one year of follow-up was evaluated. The multivariable Poisson regression model was used for calculating the incidence rate (IR) and the incidence rate ratio (IRR) with an adjustment for confounding factors. Results: We included 316 COPD patients (166 from the CICP and 150 from the GCP). During the year of follow-up, the CICP patients had 50% fewer emergency visits and hospitalizations than patients from the GCP (IRR=0.50, 95%CI: 0.29-0.87, p=0.014). Conclusions: COPD patients in the CICP had fewer emergency visits and hospitalizations due to exacerbations. Prospective clinical studies are required to confirm the results and to evaluate the factors that contribute to the differences.
Autoantibodies against tumor‐associated antigens combined with microRNAs in detecting esophageal squamous cell carcinoma

Esophageal carcinoma (EC) is a common malignant disease worldwide, especially in China. There is currently no specific blood test for detecting EC. Autoantibodies against tumor‐associated antigens (TAAbs) and microRNAs (miRNAs) are promising markers for cancer diagnosis and this study focuses on combining TAAbs and miRNAs to evaluate the diagnostic value in esophageal squamous cell carcinoma (ESCC). The expression levels of seven TAAbs and five microRNAs in plasmas from 125 patients diagnosed with ESCC and 125 healthy individuals were detected by enzyme‐linked immunosorbent assay (ELISA) and reverse transcription quantitative‐polymerase chain reaction (RT‐qPCR), respectively. The receiver operating characteristic (ROC) analysis was applied to estimate the diagnostic value of these markers for distinguishing ESCC patients from normal individuals. Logistic regression analysis was performed to generate prediction model and calculate the probability of individuals being diagnosed with ESCC. Three panels were established including four TAAbs, three miRNAs, and three TAAbs combined with three miRNAs. The panel consisting of three TAAbs (HCCR, C‐myc, and MDM2) and three miRNAs (miR‐21, miR‐223, and miR‐375) attained great diagnostic value for ESCC, with an area under the receiver operating characteristic curve (AUC) of 0.89 (95% CI: 0.85‐0.93) with the sensitivity of 69%, the specificity of 90%, the PPV of 83%, the NPV of 79%, and the coincidence rate of 81%. The optimal panel of six‐member markers was able to effectively discriminate the patients with ESCC from normal individuals, especially for early esophageal squamous cell carcinoma.
Wortmannin targeting phosphatidylinositol 3‐kinase suppresses angiogenic factors in shear‐stressed endothelial cells

Modifications on shear stress‐based mechanical forces are associated with pathophysiological susceptibility and their effect on endothelial cells (EC) needs to be better addressed looking for comprehending the cellular and molecular mechanisms. This prompted us to better evaluate the effects of shear stress in human primary venous EC obtained from the umbilical cord, using an in vitro model to mimic the laminar blood flow, reaching an intensity 1–4 Pa. First, our data shows there is a significant up‐expression of phosphatidylinositol 3‐kinase (PI3K) in shear‐stressed cells culminating downstream with an up‐phosphorylation of AKT and up‐expression of MAPK‐ERK, concomitant to a dynamic cytoskeleton rearrangement upon integrin subunits (α4 and ß 3) requirements. Importantly, the results show there is significant involvement of nitric oxide synthase (eNOS), nNOS, and vascular endothelial growth factors receptor 2 (VEGFR2) in shear‐stressed EC, while cell cycle‐related events seem to being changed. Additionally, although diminution of 5‐hydroxymethylcytosine in shear‐stressed EC, suggesting a global repression of genes transcription, the promoters of PI3K and eNOS genes were significantly hydroxymethylated corroborating with their respective transcriptional profiles. Finally, to better address, the pivotal role of PI3K in shear‐stressed EC we have revisited these biological issues by wortmannin targeting PI3K signaling and the data shows a dependency of PI3K signaling in controlling the expression of VGFR1, VGFR2, VEGF, and eNOS, once these genes were significantly suppressed in the presence of the inhibitor, as well as transcripts from Ki67 and CDK2 genes. Finally, our data still shows a coupling between PI3K and the epigenetic landscape of shear‐stressed cells, once wortmannin promotes a significant suppression of ten‐11 translocation 1 (TET1), TET2, and TET3 genes, evidencing that PI3K signaling is a necessary upstream pathway to modulate TET‐related genes. In this study we determined the major mechanotransduction pathway by which blood flow driven shear stress activates PI3K which plays a pivotal role on guaranteeing endothelial cell phenotype and vascular homeostasis, opening novel perspectives to understand the molecular basis of pathophysiological disorders related with the vascular system.
Higher Plaque Burden of Middle Cerebral Artery Is Associated With Recurrent Ischemic Stroke

Supplemental Digital Content is available in the text. Background and Purpose— This study aims to investigate the association between the characteristics of atherosclerotic plaques of middle cerebral artery and recurrent ischemic stroke using magnetic resonance vessel wall imaging. Methods— One hundred and five patients with ischemic stroke attributed to middle cerebral artery plaque underwent high-resolution black-blood magnetic resonance vessel wall imaging. They were divided into group 1, with the first episode of acute stroke (imaging within 4 weeks of stroke, n=44); group 2, with recurrent acute stroke (n=29); and group 3, with chronic stroke (imaging after 3 months of stroke, n=32). Plaque characteristics including plaque area, plaque burden, contrast-enhancement ratio, eccentricity, and degree of stenosis were measured and compared across 3 groups. Association between plaque characteristics and recurrent strokes was investigated by multivariate analysis. Results— Plaque burden was significantly greater in recurrent stroke group than the other 2 groups (median: group 2, 82.7%, versus group 1, 76.3%, and group 3, 73.4%; P=0.001). Patients with acute stroke had higher enhancement ratio than patients with chronic stroke (median: group 1, 1.59, and group 2, 1.90, versus group 3, 1.33; P=0.014). Comparing to first-onset acute stroke patients, recurrent stroke patients were older, more likely with female sex and hypertension, and had higher plaque burden. After adjustment of clinical factors, plaque burden was the only independent imaging feature associated with recurrent stroke (odds ratio, 2.26, per 10% increase [95% CI, 1.03–4.96]; P=0.042). Conclusions— Higher plaque burden of middle cerebral artery identified on magnetic resonance vessel wall imaging is independently associated with recurrent ischemic stroke.
Temporal convolutional networks allow early prediction of events in critical care

OBJECTIVE Clinical interventions and death in the intensive care unit (ICU) depend on complex patterns in patients' longitudinal data. We aim to anticipate these events earlier and more consistently so that staff can consider preemptive action. MATERIALS AND METHODS We use a temporal convolutional network to encode longitudinal data and a feedforward neural network to encode demographic data from 4713 ICU admissions in 2014-2018. For each hour of each admission, we predict events in the subsequent 1-6 hours. We compare performance with other models including a recurrent neural network. RESULTS Our model performed similarly to the recurrent neural network for some events and outperformed it for others. This performance increase was more evident in a sensitivity analysis where the prediction timeframe was varied. Average positive predictive value (95% CI) was 0.786 (0.781-0.790) and 0.738 (0.732-0.743) for up- and down-titrating FiO2, 0.574 (0.519-0.625) for extubation, 0.139 (0.117-0.162) for intubation, 0.533 (0.492-0.572) for starting noradrenaline, 0.441 (0.433-0.448) for fluid challenge, and 0.315 (0.282-0.352) for death. DISCUSSION Events were better predicted where their important determinants were captured in structured electronic health data, and where they occurred in homogeneous circumstances. We produce partial dependence plots that show our model learns clinically-plausible associations between its inputs and predictions. CONCLUSION Temporal convolutional networks improve prediction of clinical events when used to represent longitudinal ICU data.
Fluorescently-labeled fremanezumab is distributed to sensory and autonomic ganglia and the dura but not to the brain of rats with uncompromised blood brain barrier

Background The presence of calcitonin gene-related peptide and its receptors in multiple brain areas and peripheral tissues previously implicated in migraine initiation and its many associated symptoms raises the possibility that humanized monoclonal anti-calcitonin gene-related peptide antibodies (CGRP-mAbs) can prevent migraine by modulating neuronal behavior inside and outside the brain. Critical to our ability to conduct a fair discussion over the mechanisms of action of CGRP-mAbs in migraine prevention is data generation that determines which of the many possible peripheral and central sites are accessible to these antibodies – a question raised frequently due to their large size. Material and methods Rats with uncompromised and compromised blood-brain barrier (BBB) were injected with Alexa Fluor 594-conjugated fremanezumab (Frema594), sacrificed 4 h or 7 d later, and relevant tissues were examined for the presence of Frema594. Results In rats with uncompromised BBB, Frema594 was similarly observed at 4 h and 7 d in the dura, dural blood vessels, trigeminal ganglion, C2 dorsal root ganglion, the parasympathetic sphenopalatine ganglion and the sympathetic superior cervical ganglion but not in the spinal trigeminal nucleus, thalamus, hypothalamus or cortex. In rats with compromised BBB, Frema594 was detected in the cortex (100 µm surrounding the compromised BBB site) 4 h but not 7 d after injections. Discussion Our inability to detect fluorescent (CGRP-mAbs) in the brain supports the conclusion that CGRP-mAbs prevent the headache phase of migraine by acting mostly, if not exclusively, outside the brain as the amount of CGRP-mAbs that enters the brain (if any) is too small to be physiologically meaningful.
β-cell mass in non-obese diabetic NOD mice

2 Boehringer Ingelheim Pharma GmbH & Co. KG, Birkendorfer Str 65, D-88397 Biberach, 8 Germany 9 10 Running title: Linagliptin preserves β-cell mass in NOD mice 11 12 Correspondence should be addressed to 13 Thomas Klein at Boehringer Ingelheim Pharma GmbH & Co. KG, 14 CardioMetabolic Diseases Research, Birkendorfer Str 65, D-88397 Biberach, Germany 15 16 Tel: +49 (7351) 54-92483 17 Fax: +49 (7351) 83-92483 18 Email: thomas_1. klein@boehringer-ingelheim.com 19 20
Does child abuse have an impact on self-esteem, depression, anxiety and stress conditions of individuals?

Background: The present study addressed the effects of child abuse in early adulthood. Aims: The purpose of the study was to determine the direct and indirect effects of child abuse on self-esteem, depression, anxiety and stress levels. Method: The participants of the study were 636 students (477 females and 159 males) studying at three different state universities in Turkey. Data were collected through ‘Childhood Trauma Questionnaire’, ‘Depression Anxiety Stress Scale (DASS)’, ‘Two-Dimensional Self-Esteem Scale (Self-Liking/Self-Competence)’ and ‘Demographic Information Form’. The obtained data were analyzed with Pearson product-moment correlation coefficient and path analysis techniques via SPSS 23 and AMOS 22. Results: Considering the relationship between the variables, child abuse was found to be negatively correlated with self-esteem, while it was positively correlated with depression, anxiety and stress. As a result of the path analysis, it was observed that child abuse affected self-esteem directly in the negative way. Throughout the analysis, self-esteem was found to have a direct and negative effect on depression, anxiety and stress, respectively. Child abuse was also found to have an indirect effect on depression, anxiety and stress. Conclusion: Self-esteem had full mediation effect between child abuse, and depression, anxiety and stress.
Time to assess the effects of sodium–glucose co‐transporter‐2 inhibitors on the ‘forgotten' right ventricle?

We read with great interest the review article authored by Lan et al., summarizing all the relevant, both experimental and clinical, data concerning the effects of sodium–glucose co-transporter-2 (SGLT-2) inhibitors on left ventricular function and the underlying pathophysiological mechanisms. It is known that patients with type 2 diabetes mellitus (T2DM), even those being newly diagnosed or without established coronary artery disease or heart failure, feature impaired right ventricular systolic and diastolic function and decreased right ventricular end-systolic and end-diastolic volumes. This close relationship has also been confirmed in patients with concomitant T2DM and heart failure with preserved ejection fraction (HFpEF), in whom T2DM is associated with significant increase in the odds for right ventricular systolic and diastolic dysfunction, independently of right ventricular afterload. Mechanisms implicated into right ventricular involvement in T2DM are metabolic (hyperglycaemia, hyperlipidaemia, and hyperinsulinaemia), inflammatory, mechanistic (left ventricular involvement), and epigenetic, constituting right ventricular dysfunction a potential marker of diabetic cardiomyopathy. Based on the established knowledge that right ventricular dysfunction is strongly associated with the corresponding risks for heart failure hospitalization and all-cause mortality in patients with HFpEF and for cardiovascular and all-cause mortality in patients with heart failure with reduced ejection fraction (HFrEF), it is deduced that the meticulous assessment of right ventricular function in patients with T2DM—especially in those with known atherosclerotic cardiovascular disease—might be of critical importance. At the same time, right ventricular function also appears as a promising treatment target. It would be therefore interesting and clinically meaningful to know whether SGLT-2 inhibitors exert beneficial effects on right ventricular function, additive to their effects on the left ventricle, along with potential interconnection with their known, favourable cardiovascular effects. Unfortunately, no such data exist in the available literature, representing a significant gap of knowledge. We hope that future studies will investigate the impact of SGLT-2 inhibition on the right ventricle and the subsequent cardiovascular implications.
Recombinant Nontypeable Genotype II Human Noroviruses in the Americas

We report multiple nontypeable genotype II noroviruses circulating in South America; nucleotides differed by >25% from those of other genotypes. These viruses have been circulating in the Americas for ≈20 years and show recombination with other genotypes. Clues to norovirus natural history can guide development of treatment and prevention plans.
Communicative cues in the absence of a human interaction partner enhance 12-month-old infants' word learning.

Is infants' word learning boosted by nonhuman social agents? An on-screen virtual agent taught infants word-object associations in a setup where the presence of contingent and referential cues could be manipulated using gaze contingency. In the study, 12-month-old Japanese-learning children (N = 36) looked significantly more to the correct object when it was labeled after exposure to a contingent and referential display versus a noncontingent and nonreferential display. These results show that communicative cues can augment learning even for a nonhuman agent, a finding highly relevant for our understanding of the mechanisms through which the social environment supports language acquisition and for research on the use of interactive screen media.
Efficacy of Hand and Foot Massage in Anxiety and Pain Management Following Laparoscopic Cholecystectomy: A Controlled Randomized Study

This study was planned and performed to evaluate the effect of foot and hand massage on pain and anxiety management, which is one of the nonpharmacological pain relief methods in patients who undergo laparoscopic cholecystectomy. The present study was designed and conducted in the randomized controlled manner to determine the impacts of foot and hand massage on postoperative pain and anxiety scores of patients who receive laparoscopic cholecystectomy. The universe of the study consisted of the patients who received laparoscopic cholecystectomy between April 2018 and January 2019. The study was completed with 196 patients as 63 patients in the foot massage group, 65 patients in the hand massage group, and 68 patients in the control group. To collect the data, the “Descriptive Characteristics Form,” “Visual Analog Scale,” and “State-Trait Anxiety Inventory” were used. The pain intensity of patients in the foot massage group and hand massage group were less than in the control group at 90 and 150 minutes after intervention (P<0.05). A significant reduction was determined in the need for analgesics for the patients in the foot massage group and hand massage group compared with the control group (P<0.05). A significant positive relationship was found between pain intensity and state anxiety levels in patients of the foot massage group and hand massage group. Foot and hand massage are influential in decreasing pain and anxiety levels after surgeries for patients who undergo laparoscopic cholecystectomy.
Examining the financial and quality performance effects of group purchasing organizations

Background Hospitals frequently enter into group purchasing organizations (GPOs) to manage supply costs, yet there is mixed evidence regarding the benefit for hospitals to participate in a GPO. However, the role of GPOs on hospital operations has expanded into dimensions of quality that have not been previously examined. Purpose The aim of this study was to examine the effect of hospital participation in a GPO, as well as GPO network characteristics, on both financial and quality performance outcomes. Approach Data from multiple secondary sources regarding hospital and GPO characteristics were used to create an unbalanced panel of hospitals from 2012 to 2015. This data set was then aggregated to the GPO network level to address questions related to network characteristics, including concentration, bed size, geographic scope, and focus. We evaluated three hospital-level outcomes: supply expense, clinical processes of care score, and patient experience score. The mean of each outcome among all hospitals in a GPO in a given year was used for analyses at the network level. We used fixed and random effect models to assess the effect of hospital characteristics and network characteristics on three measures of financial and quality performance. Results We found no difference between GPO and non-GPO hospitals for any of the outcomes. However, analyses at the network level revealed network characteristics, including concentration, size, and scope, that affected both supply expense and patient experience scores, but not clinical processes of care. Conclusions These results indicate that GPO participation may be motivated for reasons beyond cost and quality performance impacts. Practice Implications Hospitals and GPOs should consider network characteristics, such as the concentration and geographical dispersion of the GPO network. Alternatively, GPOs may seek to develop homogeneously sized networks dispersed locally in order to best deliver both financial and quality benefits to their members.
Combined brilliant blue G and xenon light induced outer retinal layer damage following macular hole surgery

We report a case of combined brilliant blue G and endoilluminator retinal toxicity in a patient who has undergone macular hole surgery. The patient developed extensive degeneration of the retinal pigment epithelium as early as 1 week following surgery that eventually lead to poor visual outcome. We look into the pathogenesis of BBG and endoilluminator causing retinal toxicity and also suggest measures to avoid this irreversible retinal damage.