Miracle-dz/UniFAR-FTUs huggingface dataset:
Effect of the COVID-19 Pandemic on Patient Volumes, Acuity, and Outcomes in Pediatric Emergency Departments

Supplemental digital content is available in the text. Objectives The aim of this study was to quantify the effect of the COVID-19 pandemic on pediatric emergency department (ED) utilization and outcomes. Methods This study is an interrupted-time-series observational study of children presenting to 11 Canadian tertiary-care pediatric EDs. Data were grouped into weeks in 3 study periods: prepandemic (January 1, 2018–January 27, 2020), peripandemic (January 28, 2020–March 10, 2020), and early pandemic (March 11, 2020–April 30, 2020). These periods were compared with the same time intervals in the 2 preceding calendar years. Primary outcomes were number of ED visits per week. The secondary outcomes were triage acuity, hospitalization, intensive care unit (ICU) admission, mortality, length of hospital stay, ED revisits, and visits for trauma and mental health concerns. Results There were 577,807 ED visits (median age, 4.5 years; 52.9% male). Relative to the prepandemic period, there was a reduction [−58%; 95% confidence interval (CI), −63% to −51%] in the number of ED visits during the early-pandemic period, with concomitant higher acuity. There was a concurrent increase in the proportion of ward [odds ratio (OR), 1.39; 95% CI, 1.32–1.45] and intensive care unit (OR, 1.20; 95% CI, 1.01–1.42) admissions, and trauma-related ED visits among children less than 10 years (OR, 1.51; 95% CI, 1.45–1.56). Mental health–related visits in children declined in the early-pandemic period (in <10 years, −60%; 95% CI, −67% to −51%; in children ≥10 years: −56%; 95% CI, −63% to −47%) relative to the pre–COVID-19 period. There were no differences in mortality or length of stay; however, ED revisits within 72 hours were reduced during the early-pandemic period (percent change: −55%; 95% CI, −61% to −49%; P < 0.001). Conclusions After the declaration of the COVID-19 pandemic, dramatic reductions in pediatric ED visits occurred across Canada. Children seeking ED care were sicker, and there was an increase in trauma-related visits among children more than 10 years of age, whereas mental health visits declined during the early-pandemic period. When faced with a future pandemic, public health officials must consider the impact of the illness and the measures implemented on children's health and acute care needs.
Dynamic Indices Fail to Predict Fluid Responsiveness in Patients Undergoing One-Lung Ventilation for Thoracoscopic Surgery

Thoracic surgery using CO2 insufflation maintains closed-chest one-lung ventilation (OLV) that may provide the necessary heart–lung interaction for the dynamic indices to predict fluid responsiveness. We studied whether pulse pressure variation (PPV) and stroke volume variation (SVV) can predict fluid responsiveness during thoracoscopic surgery. Forty patients were enrolled in the study. OLV was performed with a tidal volume of 6 mL/kg at a positive end-expiratory pressure of 5 cm H2O, while CO2 was insufflated to the contralateral side at 8 mm Hg. Patients whose stroke volume index (SVI) increased ≥15% after fluid challenge (7 mL/kg) were defined as fluid responders. The predictive ability of PPV and SVV on fluid responsiveness was investigated using the area under the receiver-operator characteristic curve (AUROC), which was also assessed according to the right or left lateral decubitus position considering the intrathoracic location of the right-sided superior vena cava. AUROCs of PPV and SVV for predicting fluid responsiveness were 0.65 (95% confidence interval 0.47–0.83, p = 0.113) and 0.64 (95% confidence interval 0.45–0.82, p = 0.147), respectively. The AUROCs of indices did not exhibit any statistical significance according to position. Dynamic indices of preload cannot predict fluid responsiveness during one-lung ventilation with CO2 gas insufflation.
GamblingLess: A Randomised Trial Comparing Guided and Unguided Internet-Based Gambling Interventions

There is little evidence relating to the effects of adding guidance to internet-based gambling interventions. The primary aim was to compare the effectiveness of an online self-directed cognitive-behavioural gambling program (GamblingLess) with and without therapist-delivered guidance. It was hypothesised that, compared to the unguided intervention, the guided intervention would result in superior improvements in gambling symptom severity, urges, frequency, expenditure, psychological distress, quality of life and help-seeking. A two-arm, parallel-group, randomised trial with pragmatic features and three post-baseline evaluations (8 weeks, 12 weeks, 24 months) was conducted with 206 gamblers (106 unguided; 101 guided). Participants in both conditions reported significant improvements in gambling symptom severity, urges, frequency, expenditure, and psychological distress across the evaluation period, even after using intention-to-treat analyses and controlling for other low- and high-intensity help-seeking, as well as clinically significant changes in gambling symptom severity (69% recovered/improved). The guided intervention resulted in additional improvements to urges and frequency, within-group change in quality of life, and somewhat higher rates of clinically significant change (77% cf. 61%). These findings, which support the delivery of this intervention, suggest that guidance may offer some advantages but further research is required to establish when and for whom human support adds value.
Amaranthus hypochondriacus L. as a Sustainable Source of Nutrients and Bioactive Compounds for Animal Feeding

With the aim to explore the use of A. hypochondriacus seeds for animal feeding, the agronomic traits, nutrients, and bioactive compounds of four accessions with different origin (India, Nebraska, Iowa, and Pennsylvania) grown in a Mediterranean environment were studied. Proximate composition was determined using the official methods of analyses, fatty acid profile by gas chromatography, total phenolic content (TPC) and the scavenging activity (DPPH• and ABTS•+) by colorimetric method. A one-way ANOVA model was performed to determine the differences between accessions. The four A. hypochondriacus accessions showed interesting seed yield results. No significant differences were observed for crude protein and crude fiber; the oil content showed the significant highest values in the seeds from Nebraska and Pennsylvania, but their nutritional characteristics were significantly different. The accession from Nebraska showed the highest oleic and linoleic acid levels, the highest values of polyunsaturated fatty acids, the best atherogenic and thrombogenic indices and hypocholesterolemic/hypercholesterolaemic ratio, and the highest TPC content. The accession from Pennsylvania showed the highest antioxidant activity and lowest peroxidation index. On the whole, A. hypochondriacus seeds can be used as pseudo-cereal to balance the animal diet and the accession should be chosen according to the different metabolic pathways of unsaturated fatty acids in ruminant and monogastric animals.
Inactivation of the Akt/FOXM1 Signaling Pathway by Panobinostat Suppresses the Proliferation and Metastasis of Gastric Cancer Cells

Gastric cancer is the fifth most common cancer and the third leading cause of cancer-related deaths worldwide. Histone deacetylase (HDAC) inhibitors are a new class of cytostatic agents available for the treatment of various cancers and diseases. Although numerous clinical and pre-clinical trials on the anticancer effects of panobinostat have been conducted, only a few reports have investigated its efficacy in gastric cancer. The present study aimed to investigate the effects of panobinostat in gastric cancer cells. Panobinostat significantly inhibited the cell viability and proliferation of the gastric cancer cell lines SNU484 and SNU638 in a dose-dependent manner; it reduced the colony-forming ability of these cells. Moreover, it induced apoptosis as indicated by increased protein levels of cleaved poly ADP-ribose polymerase and cleaved caspase-3. Panobinostat induced the G2/M cell cycle arrest in SNU484 and SNU638 cells and subsequently decreased the G2/M phase regulatory-associated protein expression of p-Wee1, Myt1, and Cdc2. Furthermore, panobinostat significantly inhibited the metastasis of SNU484 and SNU638 cells by regulating the expression of MMP-9 and E-cadherin. Further, it decreased the protein levels of p-Akt and forkhead box protein M1 (FOXM1). These effects were reversed by the Akt agonist SC79 and were accelerated by the Akt inhibitor LY2940002. Moreover, tumor growth in xenograft animal experiments was suppressed by panobinostat. These results indicated that panobinostat inhibits the proliferation, metastasis, and cell cycle progression of gastric cancer cells by promoting apoptosis and inactivating Akt/FOXM1 signaling. Cumulatively, our present study suggests that panobinostat is a potential drug for the treatment of gastric cancer.
A role for sex‐determination genes in life history evolution? Doublesex mediates sexual size dimorphism in the gazelle dung beetle

An organism's fitness depends strongly on its age and size at maturation. Although the evolutionary forces acting on these critical life history traits have been heavily scrutinized, the developmental mechanisms underpinning intraspecific variation in adult size and development time remain much less well‐understood. Using RNA interference, I here show that the highly conserved sex‐determination gene doublesex (dsx) mediates sexual size dimorphism (SSD) in the gazelle dung beetle Digitonthophagus gazella. Because doublesex undergoes sex‐specific splicing and sex‐limited isoforms regulate different target genes, this suggests that dsx contributes to the resolution of intralocus sexual conflict in body size. However, these results contrast with previous studies demonstrating that dsx does not affect body size or SSD in Drosophila. This indicates that intraspecific body size variation is underlain by contrasting developmental mechanisms in different insect lineages. Furthermore, although male D. gazella have a longer development time than females, sexual bimaturism was not affected by dsx expression knockdown. In addition, and in contrast to secondary sexual morphology, dsx did not significantly affect nutritional plasticity in life history. Taken together, these findings indicate that dsx signalling contributes to intraspecific life history variation but that dsx's function in mediating sexual dimorphism in life history differs among traits and species. More generally, these findings suggest that genes ancestrally tasked with sex determination have been co‐opted into the developmental regulation of life history traits and may represent an underappreciated mechanism of life history evolution.
How Are Sports-Trackers Used by Runners? Running-Related Data, Personal Goals, and Self-Tracking in Running

The purpose of this research is to explore the roles that sports trackers and running-related data play in runners’ personal goal achievement. A two-week diary study and semi-structured interviews were conducted with 22 runners to explore how runners engage with their running-related data to set and achieve their running goals. We found that participants pursued and transitioned between different running goals as their needs, abilities, and surrounding environment changed. We also found multiple motivations that shaped the use of sports trackers. We identified two main categories in runners’ motivations for using trackers and data to achieve their goals. These categories were (i) documenting and tracking in running, and (ii) supporting goal-oriented reflections and actions, with various reasons for use while preparing for and during running. This study provides insights into the psychological effects of running-related data and signals practical implications for runners and developers of tracking technology.
Chikungunya Beyond the Tropics: Where and When Do We Expect Disease Transmission in Europe?

Chikungunya virus disease (chikungunya) is a mosquito-borne infectious disease reported in at least 50 countries, mostly in the tropics. It has spread around the globe within the last two decades, with local outbreaks in Europe. The vector mosquito Aedes albopictus (Diptera, Culicidae) has already widely established itself in southern Europe and is spreading towards central parts of the continent. Public health authorities and policymakers need to be informed about where and when a chikungunya transmission is likely to take place. Here, we adapted a previously published global ecological niche model (ENM) by including only non-tropical chikungunya occurrence records and selecting bioclimatic variables that can reflect the temperate and sub-tropical conditions in Europe with greater accuracy. Additionally, we applied an epidemiological model to capture the temporal outbreak risk of chikungunya in six selected European cities. Overall, the non-tropical ENM captures all the previous outbreaks in Europe, whereas the global ENM had underestimated the risk. Highly suitable areas are more widespread than previously assumed. They are found in coastal areas of the Mediterranean Sea, in the western part of the Iberian Peninsula, and in Atlantic coastal areas of France. Under a worst-case scenario, even large areas of western Germany and the Benelux states are considered potential areas of transmission. For the six selected European cities, June–September (the 22th–38th week) is the most vulnerable time period, with the maximum continuous duration of a possible transmission period lasting up to 93 days (Ravenna, Italy).
Changes in presentation, presenting severity and disposition among patients accessing emergency services during the first months of the COVID-19 pandemic in Calgary, Alberta: a descriptive study

Background: The COVID-19 pandemic has resulted in unique pressures on the emergency services system. This study describes changes in the presentation, presenting severity and disposition of patients accessing emergency services in Calgary, Alberta, during the first wave of the pandemic. Methods: In this descriptive study, we constructed a population cohort of all patients who accessed emergency services by calling emergency medical services (EMS) (ambulance service that provides prehospital treatment and transport to medical facilities) or presenting directly to an emergency department (4 adult and 1 pediatric) or 2 urgent care centres in Calgary during the exposure period (December 2019 to June 2020) compared to 2 historical control periods (December to June, 2017–2018 and 2018–2019) combined. Outcomes included frequency of presentation, system flow indicators, patient severity, disposition and mortality. We used a locally estimated scatterplot smoothing function to visualize trends. We described differences at the maximum and minimum point of the exposure period compared to the control period. Results: A total of 1 127 014 patient encounters were included. Compared to the control period, there was a 61% increase in the number of patients accessing EMS and a 35% decrease in the number of those presenting to an adult emergency department or urgent care centre in the COVID-19 period. The proportion of EMS calls for the highest-priority patients remained stable, whereas the proportion of patients presenting to an emergency department or urgent care centre with the highest-priority triage classification increased transiently by 0.9 percentage points (increase of 89%). A smaller proportion of patients were transported by EMS (decrease of 21%), and a greater proportion of emergency department patients were admitted to hospital (increase of 25%). After the first case was reported, the mortality rate among EMS patients increased by 265% (3.4 v. 12.4 per 1000 patient encounters). Interpretation: The first wave of the COVID-19 pandemic was associated with substantial changes in the frequency and disposition of patients accessing emergency services. Further research examining the mechanism of these observations is important for mitigating the impact of future pandemics.
Vitamin D and Folate as Predictors of MMSE in Alzheimer’s Disease: A Machine Learning Analysis

Vitamin D (VD) and micronutrients, including folic acid, are able to modulate both the innate and the adaptive immune responses. Low VD and folic acid levels appear to promote cognitive decline as in Alzheimer’s disease (AD). A machine learning approach was applied to analyze the impact of various compounds, drawn from the blood of AD patients, including VD and folic acid levels, on the Mini-Mental State Exam (MMSE) in a cohort of 108 patients with AD. The first analysis was aimed at predicting the MMSE at recruitment, whereas a second investigation sought to predict the MMSE after a 4 year follow-up. The simultaneous presence of low levels of VD and folic acid allow to predict MMSE, suggestive of poorer cognitive function. Such results suggest that the low levels of VD and folic acid could be associated with more severe cases of cognitive impairment in AD. It could be hypothesized that simultaneous supplementation of VD and folic acid could slow down the progression of cerebral degeneration at least in a subset of AD individuals.
Therapeutics Targeting the Core Apoptotic Machinery

Simple Summary Cancer develops when the balance between cell death and cell division in tissues is dysregulated. A key focus of cancer drug discovery is identifying therapeutic agents which will selectively kill and eliminate cancer cells from the body. A number of proteins can prevent the death of cancer cells and developing inhibitors against these proteins to promote cancer cell death is a focus of recent drug discovery efforts. This review aims to summarize the key targets being explored, the drug development approaches being adopted, and the success or limitations of agents currently approved or in clinical development. Abstract Therapeutic targeting of the apoptotic pathways for the treatment of cancer is emerging as a valid and exciting approach in anti-cancer therapeutics. Accumulating evidence demonstrates that cancer cells are typically “addicted” to a small number of anti-apoptotic proteins for their survival, and direct targeting of these proteins could provide valuable approaches for directly killing cancer cells. Several approaches and agents are in clinical development targeting either the intrinsic mitochondrial apoptotic pathway or the extrinsic death receptor mediated pathways. In this review, we discuss the main apoptosis pathways and the key molecular targets which are the subject of several drug development approaches, the clinical development of these agents and the emerging resistance factors and combinatorial treatment approaches for this class of agents with existing and emerging novel targeted anti-cancer therapeutics.
Identification of High-Risk Human Papillomavirus DNA, p16, and E6/E7 Oncoproteins in Laryngeal and Hypopharyngeal Squamous Cell Carcinomas

Human papillomavirus (HPV) was proven to play a significant role in cancer development in the oropharynx. However, its role in the development of laryngeal (LSCC) and hypopharyngeal squamous cell carcinoma (HPSCC) remains to be clarified. High-risk HPV (HR-HPV) viral proteins E6 and E7 are considered to be pertinent to HPV-related carcinogenesis. Hence, our aim was to estimate LSCC and HPSCC for HR-HPV DNA, p16, and E6/E7 oncoprotein status by using molecular virology and immunohistochemistry methods. The prevalence of HPV16 infection was 22/41 (53.7%) and 20/31 (64.5%) for LSCC and HPSCC, accordingly. The majority of HPV16+ tumor samples were stage III or IV. In most samples, the presence of either HPV16 E6 or HPV16 E7 viral protein in dysplastic or tumor cells was confirmed using immunohistochemistry. Our results suggest a high prevalence of HPV16 as a primary HR-HPV type in LSCC and HPSCC. The lack of HPV E6/E7 oncoproteins in some tumor samples may suggest either the absence of viral integration or the presence of other mechanisms of tumorigenesis. The utilization of p16 IHC as a surrogate marker of HR-HPV infection is impractical in LSCC and HPSCC.
Rotterdam and Marshall Scores for Prediction of in-hospital Mortality in Patients with Traumatic Brain Injury: An observational study

ABSTRACT Background: We aimed to assess the prognostic value of Rotterdam and Marshall scoring systems to predict in-hospital mortality in patients with traumatic brain injury (TBI). Methods: A retrospective analysis was conducted for patients with TBI who underwent head computerized tomography (CT) scan at a Level I trauma center between 2011 and 2018. Receiver operating characteristic (ROC) curves were used to determine the cutoff values for predicting in-hospital mortality. Results: A total of 1035 patients with TBI were included with a mean age of 30 years. The mean Rotterdam and Marshall scores were higher among non-survivors (p = .001). Patients with higher Rotterdam (>3) or Marshall (>2) CT scores were older, had higher injury severity scores and in-hospital mortality and had lower GCS and blood ethanol levels than those with lower scores. The cutoff point of Rotterdam score was 3.5 (sensitivity, 61.2%; specificity, 85.6%) and Marshall score was 2.5 (74.3% sensitivity and 76.3% specificity). Multivariable logistic regression analyses showed that Marshall and Rotterdam scoring systems were independent predictors of mortality (odds ratio 8.4; 95% confidence interval 4.95–14.17 and odds ratio 4.4; 95% confidence interval 2.36–9.39, respectively). Conclusion: Rotterdam and Marshall CT scores have independent prognostic values in patients with TBI even in alcoholic patients.
Multi-Solvent Extraction Procedure for the Pioneer Fecal Metabolomic Analysis—Identification of Potential Biomarkers in Stable Kidney Transplant Patients

Metabolic alteration plays a functional role in kidney allograft complications. Metabolomics is a promising high-throughput approach in nephrology but is still limited by the lack of overlap in metabolite coverage. We performed an untargeted fecal metabolomic analysis of forty stable kidney allograft recipients and twenty non-transplant controls. First, we applied the ultra-high performance liquid chromatography (UHPLC) analysis coupled with the Diod Array detector. The potential biomarkers were then collected and identified by gas chromatography-mass spectrometry (GCMS). In order to allow for complete coverage of the fecal polar and non-polar metabolites, the performance of five organic solvents with increasing polarity was investigated successively. UHPLC analysis revealed that the fecal metabolite profiles following the five extractions were significantly different between controls and kidney allografts. GC-MS analysis showed that the best predictors’ metabolites belonged mainly to long-chain fatty acids, phenolic compounds, and amino acids. Collectively, our results showed the efficiency of our pioneer method to successfully discriminate stable kidney-transplant recipients from controls. These findings suggest that distinct metabolic profiles mainly affect fatty acid biosynthesis and amino acid metabolism. In such a context, the novel insights into metabolomic investigation may be a valuable tool that could provide useful new relevant biomarkers for preventing kidney transplant complications.