Miracle-dz/UniFAR-FTUs huggingface dataset:
Evaluating Vitamin C in Septic Shock: A Randomized Controlled Trial of Vitamin C Monotherapy*

OBJECTIVES: To determine whether IV vitamin C therapy reduces 28-day mortality in patients with septic shock. DESIGN: Multicenter, double-blinded, randomized controlled trial. SETTING: One academic medical ICU and four community ICUs. PATIENTS: Of 167 adult patients within 24 hours of vasopressor initiation for septic shock, 126 consented to participation, and 124 received study drug and were included in analysis. INTERVENTIONS: IV vitamin C (10 mg/mL in normal saline) administered as a 1,000-mg bolus over 30 minutes followed by continuous infusion of 250 mg/hr for 96 hours or placebo of equal volumes of normal saline. MEASUREMENTS AND MAIN RESULTS: Of 124 subjects receiving study drug and included in analysis, 60 received vitamin C and 64 placebo. The primary outcome of all-cause 28-day mortality (vitamin C, 26.7%; placebo, 40.6%; p = 0.10) was lower in the vitamin C arm but did not reach statistical significance. Initiation of renal replacement therapy was higher in the vitamin C arm (vitamin C, 16.7%; placebo, 3.3%; p = 0.015), as was volume of fluid administration within 6 hours of study drug initiation (vitamin C, 1.07 L; placebo, 0.76 L; p = 0.03). There were no statistically significant differences in other secondary outcomes. In post hoc subgroup analysis, there was a decrease in 28-day mortality in the vitamin C arm among patients requiring positive-pressure ventilation at the time of enrollment (vitamin C, 36.3%; placebo, 60.0%; p = 0.05). This trial is registered at clinicaltrials.gov under identifier NCT03338569. CONCLUSIONS: Vitamin C monotherapy failed to significantly reduce mortality in septic shock patients as hypothesized. Our findings do not support its routine clinical use for this purpose.
Trophic interactions with heterotrophic bacteria limit the range of Prochlorococcus

Significance Prochlorococcus is the smallest and most abundant photosynthetic organism on Earth and is thought to be confined to low-latitude regions by its requirement for warm waters. Latitudinal transects in the North Pacific, however, demonstrate that the poleward decrease of this species occurs across a wide range of temperatures. An additional mechanism is likely required. We use theory, computational models, and additional observational data to suggest that the poleward decrease is caused by an ecological interaction: a shared predator which consumes both Prochlorococcus and similar-sized heterotrophic bacteria. Understanding the fate of this organism requires a knowledge of the interconnected ecosystem of other organisms, where both direct and indirect interactions control community structure. Prochlorococcus is both the smallest and numerically most abundant photosynthesizing organism on the planet. While thriving in the warm oligotrophic gyres, Prochlorococcus concentrations drop rapidly in higher-latitude regions. Transect data from the North Pacific show the collapse occurring at a wide range of temperatures and latitudes (temperature is often hypothesized to cause this shift), suggesting an ecological mechanism may be at play. An often used size-based theory of phytoplankton community structure that has been incorporated into computational models correctly predicts the dominance of Prochlorococcus in the gyres, and the relative dominance of larger cells at high latitudes. However, both theory and computational models fail to explain the poleward collapse. When heterotrophic bacteria and predators that prey nonspecifically on both Prochlorococcus and bacteria are included in the theoretical framework, the collapse of Prochlorococcus occurs with increasing nutrient supplies. The poleward collapse of Prochlorococcus populations then naturally emerges when this mechanism of “shared predation” is implemented in a complex global ecosystem model. Additionally, the theory correctly predicts trends in both the abundance and mean size of the heterotrophic bacteria. These results suggest that ecological controls need to be considered to understand the biogeography of Prochlorococcus and predict its changes under future ocean conditions. Indirect interactions within a microbial network can be essential in setting community structure.
Predictive Sentence Context Reduces Listening Effort in Older Adults With and Without Hearing Loss and With High and Low Working Memory Capacity

Objectives: Listening effort is needed to understand speech that is degraded by hearing loss, a noisy environment, or both. This in turn reduces cognitive spare capacity, the amount of cognitive resources available for allocation to concurrent tasks. Predictive sentence context enables older listeners to perceive speech more accurately, but how does contextual information affect older adults’ listening effort? The current study examines the impacts of sentence context and cognitive (memory) load on sequential dual-task behavioral performance in older adults. To assess whether effects of context and memory load differ as a function of older listeners’ hearing status, baseline working memory capacity, or both, effects were compared across separate groups of participants with and without hearing loss and with high and low working memory capacity. Design: Participants were older adults (age 60–84 years; n = 63) who passed a screen for cognitive impairment. A median split classified participants into groups with high and low working memory capacity. On each trial, participants listened to spoken sentences in noise and reported sentence-final words that were either predictable or unpredictable based on sentence context, and also recalled short (low-load) or long (high-load) sequences of digits that were presented visually before each spoken sentence. Speech intelligibility was quantified as word identification accuracy, and measures of listening effort included digit recall accuracy, and response time to words and digits. Correlations of context benefit in each dependent measure with working memory and vocabulary were also examined. Results: Across all participant groups, accuracy and response time for both word identification and digit recall were facilitated by predictive context, indicating that in addition to an improvement in intelligibility, listening effort was also reduced when sentence-final words were predictable. Effects of predictability on all listening effort measures were observed whether or not trials with an incorrect word identification response were excluded, indicating that the effects of predictability on listening effort did not depend on speech intelligibility. In addition, although cognitive load did not affect word identification accuracy, response time for word identification and digit recall, as well as accuracy for digit recall, were impaired under the high-load condition, indicating that cognitive load reduced the amount of cognitive resources available for speech processing. Context benefit in speech intelligibility was positively correlated with vocabulary. However, context benefit was not related to working memory capacity. Conclusions: Predictive sentence context reduces listening effort in cognitively healthy older adults resulting in greater cognitive spare capacity available for other mental tasks, irrespective of the presence or absence of hearing loss and baseline working memory capacity.
Impact of COVID-19 on in-hospital cardiac arrest outcomes: An updated meta-analysis

Background The main purposes of this meta-analysis are to update the information about the impact of coronavirus disease 2019 (COVID-19) pandemic on outcomes of in-hospital cardiac arrest (IHCA) and to investigate the impact of being infected by by severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) on IHCA outcomes. Methods The current meta-analysis is an update and follows the recommendations of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Results In analyses, pre- and intra-COVID-19 periods were observed for: shockable rhythms in 17.6% vs. 16.2% (odds ratio [OR]: 1.11; 95% confidence interval [CI]: 0.71–1.72; p = 0.65), return of spontaneous circulation (ROSC) in 47.4% vs. 44.0% (OR: 1.36; 95% CI: 0.90–2.07; p = 0.15), 30-day mortality in 59.8% vs. 60.9% (OR: 0.95; 95% CI: 0.75–1.22; p = 0.69) and overall mortality 75.8% vs. 74.7% (OR: 0.80; 95% CI: 0.49–1.28; p = 0.35), respectively. In analyses, SARS-CoV-2 positive and negative patients were observed for: shockable rhythms in 9.6% vs. 19.8% (OR: 0.51; 95% CI: 0.35–0.73; p < 0.001), ROSC in 33.9% vs. 52.1% (OR: 0.47; 95% CI: 0.30–0.73; p < 0.001), 30-day mortality in 77.2% vs. 59.7% (OR: 2.08; 95% CI: 1.28–3.38; p = 0.003) and overall mortality in 94.9% vs. 76.7% (OR: 3.20; 95% CI: 0.98–10.49; p = 0.05), respectively. Conclusions Despite ROSC, 30-day and overall mortality rate were not statistically different in prevs. intra-COVID-19 periods, a lower incidence of ROSC and higher 20-day mortality rate were observed in SARS-CoV-2 (+) compared to SARS-CoV-2 (−) patients.
Prognostic value of the MELD‐XI score in patients undergoing cardiac resynchronization therapy

Multi‐organ dysfunction was recently reported to be a common condition in patients with heart failure (HF). The Model for End‐stage Liver Disease eXcluding International normalized ratio (MELD‐XI) score reflects liver and kidney function. The prognostic relevance of this score has been reported in patients with a variety of cardiovascular diseases who are undergoing interventional therapies. However, the relationship between the severity of hepatorenal dysfunction assessed by the MELD‐XI score and the long‐term clinical outcomes of HF patients receiving cardiac resynchronization therapy (CRT) has not been evaluated.
FKBP‐type peptidyl‐prolyl cis‐trans isomerase interacts with the movement protein of tomato leaf curl New Delhi virus and impacts viral replication in Nicotiana benthamiana

Abstract Begomoviruses belonging to the family Geminiviridae are plant‐infecting DNA viruses. Begomoviral movement protein (MP) has been reported to be required for virus movement, host range determination, and symptom development. In the present study, the FK506‐binding protein (FKBP)‐type peptidyl‐prolyl cis‐trans isomerase (NbFKPPIase) of Nicotiana benthamiana was identified by a yeast two‐hybrid screening system using the MP of tomato leaf curl New Delhi virus (ToLCNDV) oriental melon (OM) isolate (MPOM) as bait. Transient silencing of the gene encoding NbFKPPIase increased replication of three test begomoviruses, and transient overexpression decreased viral replication, indicating that NbFKPPIase plays a role in defence against begomoviruses. However, infection of N. benthamiana by ToLCNDV‐OM or overexpression of the gene encoding MPOM drastically reduced the expression of the gene encoding NbFKPPIase. Fluorescence resonance energy transfer analysis revealed that MPOM interacted with NbFKPPIase in the periphery of cells. Expression of the gene encoding NbFKPPIase was induced by salicylic acid but not by methyl jasmonate or ethylene. Moreover, the expression of the gene encoding NbFKPPIase was down‐regulated in response to 6‐benzylaminopurine and up‐regulated in response to gibberellin or indole‐3‐acetic acid, suggesting a role of NbFKPPIase in plant development. Transcriptome analysis and comparison of N. benthamiana transient silencing and overexpression of the gene encoding MPOM led to the identification of several differentially expressed genes whose functions are probably associated with cell cycle regulation. Our results indicate that begomoviruses could suppress NbFKPPIase‐mediated defence and biological functions by transcriptional inhibition and physical interaction between MP and NbFKPPIase to facilitate infection.
A Model for Early Endoscopic Detection of High-Risk Gastroesophageal Varices in Children With Biliary Atresia

ABSTRACT Objective: In children with biliary atresia and portal hypertension, progression to gastroesophageal varices carrying a risk of bleeding depends on age, total serum bilirubin concentration and initial endoscopic features. We report an attempt to use these factors for early detection of high-risk varices (HRVs). Methods: Based on different combinations of these factors, a model was set to estimate the probabilities of emergence of HRVs at various time intervals. A 10% probability was chosen to set the date of the next endoscopy in children who did not display HRVs initially. A total of 113 children without HRVs who underwent their first endoscopy before age 8 in 2013–2020 were included. A comparison was made with children seen during the period 1990–2012 when this model was not used. Results: In all, 65 of the 113 children underwent one to five additional endoscopies at dates set according to the model. The emergence of HRVs was recorded in 22 children after a mean interval of 14 months and was managed by endoscopic primary prophylaxis in all but one who underwent liver transplantation. Three other children bled before the next planned endoscopy. Compared with 175 children of the same age ranges without HRVs in the period 1990–2012, the use of the model was associated with a faster detection of HRVs with a lower number of endoscopic procedures (P = 0.0022 and P = 0.023, respectively). Conclusion: The results suggest that the model reported may be a useful tool for the early detection of HRVs to allow primary prophylaxis of bleeding.
Clinical characteristics and outcomes in hospitalized adult influenza patients: an observational study from Norway 2014–2018

Abstract Background Seasonal influenza causes substantial numbers of hospitalizations annually. We have characterized the clinical picture and treatment practice in hospitalized adult influenza patients and assessed whether clinical risk scores on admission or influenza type were associated with severe outcomes. Methods Clinical characteristics and risk scores on admission (CRB65, CRB, SIRS and quick Sequential Organ Failure Assessment [qSOFA]), treatment and severe outcomes (defined as: stay in intensive care unit (ICU), receiving oxygen supplementation or staying ≥5 days in hospital), were recorded in patients hospitalized with influenza at Oslo University Hospital, Norway, between 2014 and 2018. Results Among the 156 included patients, 52.6% had influenza A(H3N2), 32.6% influenza B and 12.8% influenza A(H1N1). Median age was 70 years and 59.6% of patients were ≥65 years. Nine (5.8%) of the patients were treated in ICU, 43.0% received oxygen and 47.4% stayed ≥5 days in hospital. Overall, 34.6% of the patients had a high CRB score on admission which was associated with stay in ICU and oxygen supplementation. Multivariate analyses identified age, and pneumonia (46.8%), but not influenza type, to be associated with severe outcomes. Antiviral treatment was given to 37.2% of the patients, while 77.6% received antibiotics. Only 25.5% of patients with influenza B received antiviral therapy. Conclusions The influenza patients were mostly elderly, and few patients were treated in ICU. A high CRB score was associated with severe outcomes with possible implications for patient monitoring. Less than 40% of the patients received antiviral therapy, whereas the majority were treated with antibiotics, indicating potential for optimising treatment strategies.
Hypercapnia: A Potential Culprit in Gray Matter Injury in Preterm Neonates?

Over the last decade, there has been increased recognition of diverse forms of primary gray matter injury (GMI) in post-preterm neonates. In this study, we aimed to assess whether early neonatal hypercapnia in the preterm infant was associated with GMI on magnetic resonance imaging (MRI) at term equivalent age. All blood gases taken during the first two weeks of life were analyzed for hypercapnia. MRI was performed at term equivalent age post-preterm infants using a unique neonatal MRI 1T scanner. The neonatal MRI scans were assessed using a standardized scoring system, the Kidokoro scoring system, a method used to assess abnormal brain metrics and the presence and severity of brain abnormalities. Subscores are assigned for different regions of the brain. Twenty-nine infants were studied, about half of whom had evidence of some gray matter abnormality. Fifteen of the infants were hypercapnic. The hypercapnic infants had significantly higher deep gray matter abnormality (DGMA) readings as compared to the non-hypercapnic infants (12[11;12] vs 10[8;11] respectively; p=0.0106). Correlations were observed between peak pCO2 over the first two weeks of life and the overall gray matter abnormality score (GMAS) at term equivalent age, and between the % of hypercapnic blood gases during the first two weeks of life and the GMAS. All of the infants in our population who had severe GMI at term equivalent age were hypercapnic in the first two weeks of life. In conclusion, our data show a correlation between early hypercapnia in preterm neonates and GMI at term equivalent age.
The effects of exercise intensity and duration on the relationship between the slow component of V̇O2 and peripheral fatigue

If the development of the oxygen uptake slow component (V̇O2SC) and muscle fatigue are related, these variables should remain coupled in a time‐ and intensity‐dependent manner. Methods: 16 participants (7 females) visited the laboratory on 7 separate occasions: (1) three 6‐minutes moderate‐intensity cycling exercise bouts proceeded by a ramp incremental test; (2‐3) 30‐minutes constant power output (PO) exercise bout to determine the maximal lactate steady state (MLSS); (4‐7) constant‐PO exercise bouts to task failure (TTF), pseudorandomized order, at (i) 15% below the PO at MLSS; (ii) 10 W below MLSS; (iii) MLSS; (iv) 10 W above MLSS (first intensity and randomized order thereafter). Neuromuscular fatigue was characterized by isometric maximal voluntary contractions and femoral nerve electrical stimulation of knee extensors to measure peripheral fatigue at baseline, at min 5, 10, 20, 30 and TTF. Pulmonary oxygen uptake (V̇O2) was continuously recorded during the constant‐PO bouts and V̇O2SC was characterized based on each individual V̇O2 kinetics during moderate transitions.
Anti-Corruption Campaign and Firm Financial Performance: Evidence From Vietnam Firms

Background Corruption affects businesses in various ways. Anti-corruption, on the other hand, can improve the institutions of the country as well as business operations. Vietnam, as a socialist-oriented country with an ongoing high-profile anti-corruption campaign, provides us a unique setting to evaluate the impacts of anti-corruption on corporate performance. Objectives We address two questions: (1) what is the effect of anti-corruption on the performance of private-owned firms in Vietnam? and (2) how does anti-corruption influence the performance of firms with state ownership (FSOs) in Vietnam? Research design To investigate the impact of anti-corruption on performance of firms with different ownership settings, we use the establishment of the Central Anti-Corruption Steering Committee of Vietnam as a quasi-natural experiment for difference-in-differences analysis. We generate treatment effects of private holding and the state block ownership. To validate the findings, we construct a novel news-based anti-corruption index from Vietnamese online newspapers and use it in a robustness test to evaluate anti-corruption’s impacts on firm performance. Results and Conclusions We find a positive impact of the anti-corruption campaign on private firms’ performance, supporting the social norm perspective of how corruption affects businesses. The empirical results indicate a negative impact of the campaign on FSOs’ performance. The findings suggest that anti-corruption benefits private firms via improving the institutional quality of the country while improving the financial transparency of FSOs. Our study provides a method for measuring anti-corruption which is virtually unobservable and absent in the literature. The findings have implications for policymaking in contemporary Vietnam.
Social and nonsocial stimuli alter the performance of bonobos during a pictorial emotional Stroop task

The emotional Stroop task is a paradigm commonly applied in human studies to investigate how emotionally laden stimuli interfere with cognitive processes. Recent modifications of this task have enabled researchers to study similar Stroop effects in zoo‐housed primates. Across three experiments using a pictorial emotional Stroop task, we investigated if the attention of bonobos was influenced by social (facial expressions during play, conflict, and neutral events) and nonsocial stimuli (a preferred food item, predator, and flower). Four bonobos successfully learned to complete the task on a touchscreen. First, we tested the bonobos on a standard color‐interference Stroop task and found that they made more errors in color‐congruent trials. Second, we included facial expressions of unknown conspecifics and found that it took the bonobos longer to select targets with play facial expressions compared to neutral expressions. Last, we included objects and found that the negative, positive and neutral objects altered performance. Our findings show that the cognitive processes of bonobos are influenced by both relevant social and nonsocial stimuli. Specifically, play faces interfered with the bonobos’ attention suggesting that these facial expressions form a salient stimulus within bonobo society. Nonsocial stimuli also altered accuracy and reaction times during the task which may be explained by their evolutionary relevance. Our results help us to better understand the (socio‐)emotional competencies of bonobos and how they respond to external stimuli. Future studies can further examine how a wider range of biologically relevant stimuli interfere with attentional processes in bonobos.
Therapeutic Potential of Emodin for Gastrointestinal Cancers

Gastrointestinal (GI) cancers cause one-third of all cancer-related deaths worldwide. Natural compounds are emerging as alternative or adjuvant cancer therapies given their distinct advantage of manipulating multiple pathways to both suppress tumor growth and alleviate cancer comorbidities; however, concerns regarding efficacy, bioavailability, and safety are barriers to their development for clinical use. Emodin (1,3,8-trihydroxy-6-methylanthraquinone), a Chinese herb-derived anthraquinone, has been shown to exert anti-tumor effects in colon, liver, and pancreatic cancers. While the mechanisms underlying emodin’s tumoricidal effects continue to be unearthed, recent evidence highlights a role for mitochondrial mediated apoptosis, modulated stress and inflammatory signaling pathways, and blunted angiogenesis. The goals of this review are to (1) highlight emodin’s anti-cancer properties within GI cancers, (2) discuss the known anti-cancer mechanisms of action of emodin, (3) address emodin’s potential as a treatment complementary to standard chemotherapeutics, (4) assess the efficacy and bioavailability of emodin derivatives as they relate to cancer, and (5) evaluate the safety of emodin.
Dementia Awareness Challenges in Sub-Saharan Africa: A Cross-Sectional Survey Conducted Among School Students in Ghana

The survey focuses on identifying dementia awareness challenges among Ghanaian school students. Data were generated in a cross-sectional survey (n = 1137). 9.3% of school students showed dementia awareness whilst the community respondents, representing both higher age and level of education, showed greater awareness (32.2%, P < .001). 45% of respondents believed in witchcraft and 57% were afraid of potentially being harmed by witchcraft. Age and education did not influence people’s belief in witchcraft. Moreover, dementia symptoms were often mistaken for witchcraft, especially by those who had encountered a person accused of witchcraft: “swearing at others” (24%), displaying “memory loss” and “confused speech” (22%), “forgetfulness” and who was seen “roaming around” (19%). Lack of dementia awareness was particularly evident among school students whereas belief in witchcraft was similar in both respondent groups. There was a correlation between low dementia awareness rates and misinterpretation of dementia symptoms with attribution to witchcraft.