Miracle-dz/UniFAR-FTUs huggingface dataset:
1H-NMR based metabolic profiles delineate the anticancer effect of vitamin C and oxaliplatin on hepatocellular carcinoma cells.

Hepatocellular carcinoma (HCC) is a leading cause of worldwide cancer death. Due to its high recurrence rate and heterogeneity, effective treatment for advanced stage of HCC is currently lacking. There are accumulating evidences showing the therapeutic potential of pharmacologic vitamin C (VC) on HCC. However, the metabolic basis underlying the anticancer property of VC remains to be elucidated. In this study, we used a high-resolution proton nuclear magnetic resonance (1H NMR) -based metabolomics technique to assess the global metabolic changes in HCC cells following VC treatment. In addition, the HCC cells were also treated with oxaliplatin (OXA) to explore the potential synergistic effect induced by the combined VC and OXA treatment. The current metabolomics data suggested different mechanisms of OXA and VC in modulating cell growth and metabolism. In general, VC treatment led to inhibition of energy metabolism via NAD+ depletion and amino-acid deprivation. On the other hand, OXA caused significant perturbation in phospholipid biosynthesis and phosphatidylcholine biosynthesis pathways. The current results highlighted glutathione metabolism and pathways related to succinate and choline may play central roles in conferring the combined effect between OXA and VC. Taken together, this study provided metabolic evidence of VC and OXA in treating HCC, and may contribute towards the potential application of combined VC and OXA as complementary HCC therapies.
Cancer incidence among seafarers and fishermen in the Nordic countries

Objectives: Maritime workers may be exposed to several occupational hazards at sea. The aim of this study was to assess cancer incidence among seafarers and fishermen in the Nordic countries and identify patterns in morbidity in the context of existing studies in this field. Methods: A cohort of 81 740 male seafarers and 66 926 male fishermen was established from census data on 15 million citizens in the five Nordic countries. Using personal identity codes, information on vital status and cancer was linked to members of the cohort from the national population and cancer registries for the follow-up period 1961–2005. Standardized incidence ratios (SIR) were calculated applying national cancer incidence rates for each country and pooling results. Results: The overall incidence of cancer was increased among the male seafarers [SIR 1.22, 95% confidence interval (CI) 1.19–1.23]. Significant excesses were observed for multiple cancer sites among the seafarers, while results for the fishermen were mixed. Lip cancer incidence was increased among both maritime populations. For mesothelioma (SIR 2.17, 95% CI 1.83–2.56 seafarers) and non-melanoma skin cancer (SIR 1.23, 95% CI 1.14–1.32 seafarers), incidence was increased among the seafarers. Conclusion: In our cohort, seafaring was associated with a higher overall incidence of cancer compared to the general population. While the majority of cancers could not be linked to specific occupational factors, increases in mesothelioma, lip and non-melanoma-skin cancer indicate previous exposure to asbestos, ultraviolet radiation and potentially also chemicals with dermal carcinogenic properties at sea.
Excretion of Toxoplasma gondii oocysts from Feral Cats in Korea

Sporulated oocysts from the feces of infected cats with Toxoplasma gondii can cause detrimental disease in both humans and animals. To investigate the prevalence of feral cats that excrete T. gondii oocysts in the feces, we examined fecal samples of 563 feral cats over a 3-year period from 2009 to 2011. Oocysts of T. gondii excreted into the feces were found from 4 of 128 cats in 2009 (3.1%) and one of 228 (0.4%) in 2010 while none of the 207 cats in 2010 were found positive with oocysts in their feces, resulting in an overall prevalence rate of 0.89% (5/563) between 2009 and 2011. Among the 5 cats that tested positive with T. gondii oocysts, 4 of the cats were male and 1 was a female with an average body weight of 0.87 kg. Numerous tissue cysts of 60 μm in diameter with thin (<0.5 μm) cyst walls were found in the brain of one of the 5 cats on necropsy 2 months after the identification of oocysts in the feces. A PCR amplification of the T. gondii-like oocysts in the feces of the positive cats using the primer pairs Tox-5/Tox-8 and Hham34F/Hham3R confirmed the presence of T. gondii oocysts in the feces. This study provides a good indication of the risk assessment of feral cats in the transmission of T. gondii to humans in Korea.
Subcellular trafficking of tubular MDM2 implicates in acute kidney injury to chronic kidney disease transition during multiple low‐dose cisplatin exposure

Acute kidney injury (AKI) is the leading cause of renal failure, and quite a few patients will advance to chronic kidney disease (CKD) in the long term. Here, we explore the roles and mechanisms of tubular epithelial cells (TECs) during repeated cisplatin (CP) induced AKI to CKD transition (AKI‐CKD). Previously, we reported that murine double minute 2 (MDM2), an E3‐ubiquitin ligase, is involved in tubulointerstitial fibrosis. However, whether tubular MDM2 is implicated in AKI‐CKD is undefined. Currently, we confirmed that during AKI‐CKD, MDM2 shifts from nucleus to cell membrane in TECs both in vivo and in vitro. Whereas regulating MDM2 distribution chemically or genetically has a prominent impact on tubular disorders. And then we investigated the mechanisms of the above findings. First, in the nucleus, repeated CP administration leads to MDM2 reduction with escalated p53 and cell cycle G2/M arrest. On the other hand, multiple CP treatment increases the level of membranous MDM2 with ensuing integrin β8 degradation and TGF‐β1 activation. More interestingly, anchoring MDM2 on cell membranes can mimic the reduction of integrin β8 arousing by repeated CP exposure. Collectively, our findings provided the evidence that tubular MDM2 subcellular shuttling is involved in AKI‐CKD through p53‐G2/M arrest and integrin β8 mediated TGF‐β1 activation.
A note on the bias of standard errors when orthogonality of mean and variance parameters is not satisfied in the mixed model for repeated measures analysis

The mixed effect models for repeated measures (MMRM) analysis is sometimes used as a primary analysis in longitudinal randomized clinical trials. The SE for the treatment effect in the MMRM analysis is usually estimated by assuming the orthogonality of the fixed effect and variance‐covariance parameters, which is the orthogonality property of a multivariate normal distribution, because of default settings of most standard statistical software. However, this property might be lost when analysis models are misspecified and/or data include missing values with the mechanism of being missing at random. In this study, we investigated the effect of the assumption of the orthogonality property on the estimation of the SE for the MMRM analysis. From simulation and case studies, it was shown that the SE with the assumption of orthogonality property had nonnegligible bias, especially when the analysis models assuming heteroscedasticity between treatment groups were applied. We also introduce the SAS code for the MMRM analysis without assuming the orthogonality property. Assuming the orthogonality property in the MMRM analysis would lead to invalid statistical inference, and it is necessary to be careful when applying the MMRM analysis with most standard software.
Feasibility of the Audio Recorded Cognitive Screen in the Assessment of Individuals Undergoing Electroconvulsive Therapy.

BACKGROUND Monitoring for cognitive deficits during a course of electroconvulsive therapy (ECT) is recommended, but cognitive assessment can be time consuming. The Audio Recorded Cognitive Screen (ARCS) is a cognitive test instrument with good psychometric properties that places minimal demands on clinicians' time, but until now, it has not been formally evaluated for monitoring cognition in the context of ECT treatment. OBJECTIVES This study aimed to assess the feasibility/utility of using the ARCS in the assessment of depressed patients undergoing ECT. METHODS Depressed patients undergoing ECT were tested with the ARCS and a comparison instrument, the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), in counterbalance order immediately before any ECT and after the sixth ECT treatment episode. Apathy (Apathy Scale) and depression (Profile of Mood states Short Form) were measured on both occasions. Analyses compared performances on the 2 cognitive instruments and examined for associations with the measures of apathy or depression. RESULTS Twenty-eight individuals (9 male, 19 female) aged 19 to 84 years underwent testing. Performances on the total ARCS were similar to those on the total RBANS, and both showed decline from baseline to follow-up. The total ARCS and RBANS measures correlated well (r = 0.75, P < 0.001). Neither apathy nor depression scores were significantly associated with scores on either the RBANS or ARCS. CONCLUSIONS The ARCS was acceptable and convenient in the assessment of cognition in patients undergoing treatment with ECT. In light of its practical advantages, further evaluation of the ARCS for detecting cognitive impairment and tracking cognitive changes during ECT seems warranted.
Dementia screening for elderly in-patients and its association with nursing care satisfaction-an observational study

Abstract Inappropriate care for patients with cognitive dysfunction in the hospital could worsen quality of care and medical service satisfaction. All elderly participants were recruited from acute wards of 5 departments in an university hospital. They were administered the Chinese version of Ascertain Dementia 8 (AD8) at admission and the Nursing Service Satisfaction Questionnaire before discharge. A total of 345 participants completed the study. There were 91 (26.4%) participants with AD8 ≥ 2, the cut-off value of high risk of dementia. The prevalence was much higher than prior community-based reports. The Nursing Service Satisfaction Score was significantly lower in AD8 ≥ 2 than in AD8 < 2 (56.99 ± 0.94 vs 60.55 ± 0.48, P < .01). Using AD8 in hospital-based screening might be more efficient than in the community in terms of cost-effectiveness due to higher positive rate and easier approach to diagnostic facilities. AD8 ≥ 2 is also an indicator to identify care dissatisfaction among inpatients. By identifying patients with cognitive dysfunction, such as its related communication barriers, care systems could be tailored for more friendly services.
Reduced delayed reward selection by Alzheimer’s disease and mild cognitive impairment patients during intertemporal decision-making

ABSTRACT Intertemporal decision-making refers to selection among options with distinct consequences over time. Older adults have to make important decisions regarding health care and finances among other difficult issues with different shorter- and longer-term outcomes. Patients with Alzheimer’s disease (AD) or mild cognitive impairment (MCI), a potential harbinger of AD, may make suboptimal decisions in complex situations, possibly due to impaired capacity for temporal discounting. This study aimed to evaluate intertemporal preferences in AD and MCI patients compared to healthy matched controls. AD or MCI patients and healthy control (HC) patients participated in a computerized, Chinese version of the Intertemporal Choice Task in which they were asked to choose between sooner-smaller (SS) and later-larger (LL) options in now-trials and not-now-trials. The main evaluation parameter was the percentage of choices for delayed rewards(%LL). AD or MCI patients tended to choose SS options in now-trials and not now-trials with greater frequency compared to HC patients. Additionally, AD and MCI patients demonstrated significantly poorer performance in several cognitive tests compared to healthy groups, including the Mini Mental State Exam (MMSE) and other tests of memory, attention and executive function. Correlational analysis revealed that poor intertemporal decision-making was associated with executive function deficits in MCI patients. Reduced intertemporal decision-making capacity in MCI may stem from impaired executive function, possibly due to frontal-parietal circuit degeneration. The cognitive and neurophysiological deficits underlying reduce decision-making capacity in AD warrant further investigation.
P50, N100, and P200 Sensory Gating in Panic Disorder

Panic disorder (PD) has been linked to abnormalities in information processing. However, only little evidence has been published for sensory gating in PD. Sensory gating describes the brain’s ability to exclude stimuli of low relevance from higher level information processing, thereby sustaining efficient cognitive processing. Deficits in sensory gating have been associated with various psychiatric conditions, most prominently schizophrenia. In this case-control event-related potential study, we tested 32 patients with PD and 39 healthy controls in a double click paradigm. Both groups were compared with regard to pre-attentive (P50), early-attentive (N100), and late-attentive (P200) sensory gating indices. Contrary to a hypothesized deficit, PD patients and healthy controls showed no differences in P50, N100 and P200 values. These results suggest that sensory gating seems to be functional across the pre-attentive, early-attentive, and late-attentive time span in this clinical population. Given this consistency across auditory sensory gating indices, further research aiming to clarify information processing deficits in PD should focus on other neurophysiological markers to investigate information processing deficits in PD (eg, P300, error-related negativity or mismatch negativity).
Temperature and pH affect copper release kinetics from copper metal foil and commercial copperware to food simulants

ABSTRACT Copper (Cu) metal and alloys are used in cookware and other food contact surfaces due to their desirable properties for various applications. However, Cu metal can ionise and subsequently transfer to food and beverages under certain conditions. Here, we tested how pH and temperature affected Cu release kinetics using model systems utilising Cu metal foil and commercially available copperware. Cu foil and copperware were exposed to food simulants composed of 3% (w:w) aqueous solutions of citric acid, malic acid, acetic acid, or deionised (DI) water at temperatures ranging from 4°C to 60°C. An additional pilot experiment tested how simulated long-term cleaning affected subsequent Cu release from lined and unlined copperware to 3% citric acid. Food simulants were then analysed by ICP-MS for total Cu. After 180 min, incubation of Cu metal foil with acid-containing food simulants at 4°C resulted in Cu release ranging from 8.7 - 14.0 µg cm−2, while 21.5–38.1 µg cm−2 was released at 60°C. In contrast, Cu transfer from metal foil to DI water was relatively low, with <0.6 µg cm−2 released after 180 min at 60°C. With citric acid food simulant, lined copperware released between 0.6 and 3.0 µg Cu cm−2 over 180 min at the set temperatures, while unlined copperware released approximately 25–45 fold higher amounts of Cu (26.9–74.6 µg cm−2) over this same time period. In contrast, use of DI water food simulant resulted in Cu release of <0.1 µg cm−2 for the lined copperware and <2 µg cm−2 for the unlined type. No significant effect of simulated long-term cleaning on Cu release from copperware was observed. These data indicate that Cu release is affected by temperature and pH, and that specific steps can be taken to limit Cu metal release from food contact surfaces to foods and beverages. Graphical Abstract
Opportunities and challenges in the therapeutic activation of human energy expenditure and thermogenesis to manage obesity

The current obesity pandemic results from a physiological imbalance in which energy intake chronically exceeds energy expenditure (EE), and prevention and treatment strategies remain generally ineffective. Approaches designed to increase EE have been informed by decades of experiments in rodent models designed to stimulate adaptive thermogenesis, a long-term increase in metabolism, primarily induced by chronic cold exposure. At the cellular level, thermogenesis is achieved through increased rates of futile cycling, which are observed in several systems, most notably the regulated uncoupling of oxidative phosphorylation from ATP generation by uncoupling protein 1, a tissue-specific protein present in mitochondria of brown adipose tissue (BAT). Physiological activation of BAT and other organ thermogenesis occurs through β-adrenergic receptors (AR), and considerable effort over the past 5 decades has been directed toward developing AR agonists capable of safely achieving a net negative energy balance while avoiding unwanted cardiovascular side effects. Recent discoveries of other BAT futile cycles based on creatine and succinate have provided additional targets. Complicating the current and developing pharmacological-, cold-, and exercise-based methods to increase EE is the emerging evidence for strong physiological drives toward restoring lost weight over the long term. Future studies will need to address technical challenges such as how to accurately measure individual tissue thermogenesis in humans; how to safely activate BAT and other organ thermogenesis; and how to sustain a negative energy balance over many years of treatment.
The Clinical and Laboratory Standards Institute Subcommittee on Antimicrobial Susceptibility Testing: Background, Organization, Functions, and Processes

The Clinical and Laboratory Standards Institute (CLSI) Subcommittee on Antimicrobial Susceptibility Testing (AST SC) is a volunteer-led, multidisciplinary consensus body that develops and publishes standards and guidelines (among other products) for antimicrobial susceptibility testing (AST) methods and results interpretation in the United States and internationally. The Subcommittee (SC) meets face-to-face twice yearly, and its working groups (WGs) are active throughout the year via teleconferences. ABSTRACT The Clinical and Laboratory Standards Institute (CLSI) Subcommittee on Antimicrobial Susceptibility Testing (AST SC) is a volunteer-led, multidisciplinary consensus body that develops and publishes standards and guidelines (among other products) for antimicrobial susceptibility testing (AST) methods and results interpretation in the United States and internationally. The Subcommittee (SC) meets face-to-face twice yearly, and its working groups (WGs) are active throughout the year via teleconferences. All meetings are open to the public. Participants include clinical microbiologists, infectious disease (ID) pharmacists, and infectious disease physicians representing the health care professions, government, and industry. Individuals who work for a company with a primary financial dependency on drug sales cannot serve as voting members, and well-defined conflict of interest polices are in place. In addition to developing and updating susceptibility breakpoints, the SC develops and validates new testing methods, provides guidance on how results should be interpreted and applied, sets quality control ranges, and educates users through seminars, symposia, and webinars. Based on its work, the SC publishes print and electronic standards and guidelines, including an annual update, the Performance Standards for Antimicrobial Susceptibility Testing (M100). This commentary will describe the background, organization, functions, and operational processes of the AST SC.
EFFECT OF IN-OVO INJECTION WITH IRON–METHIONINE CHELATES OR IRON NANO-PARTICLES AND POST HATCH DIETARY FOLIC ACID ON GROWTH PERFORMANCE AND PHYSIOLOGICAL RESPONSES OF BROILER CHICKENS

A study was carried out to evaluate the effect of in-ovo injection of iron–methionine chelates (Fe-Meth) or iron nano-particles (FeNPs) and post hatch feeding with diets fortified with folic acid on productive performance and some physiological responses of Ross broiler chickens. A total of 450 fertile eggs were allocated to 5 treatment groups in the incubator, each of which included 3 replicates (30 eggs each). Experimental treatments consisted of a 5 × 2 factorial arrangement design with 5 levels of in-ovo injection solutions at day seven of incubation and two dietary levels of folic acid (FA) (0.0 or 0.5g/kg, diet) after hatching. In-ovo injection treatments were divided into 5 groups: control non- injected (T1), injected with 0.1 ml physiological saline (T2), sham-injected control (T3),injected with 0.1 ml of 75 ppb of iron nano-particles (T4, FeNPs), while the last group (T5) was injected with 0.1 ml of 75 ppb organic iron (Fe- meth). Results showed that in-ovo injection of different iron sources significantly improved live body weight and weight gain of broiler chicks, and enhanced FCR at 3 and 5 weeks of age compared to other groups. Broilers fed folic acid fortified diets displayed significantly heavier Live body weight (LBW) and body weight gain (BWG) than the those fed the control un-supplemented diet. The combined interaction effect of in-ovo iron injection and dietary folic acid supplementation showed the best productive performance figures during the whole experimental period. Different iron sources had no significant effect on all plasma protein fraction, Lipids profile except a higher concentration of high density lipoprotein (HDL) in plasma recorded in-ovo injection of different iron sources compared with different controls. Plasma hemoglobin, globulin fractions(α, β, and γ-globulin), transferrin and Tri-iodothyronine concentration were significantly higher in both injected groups compared to the different control groups. Birds fed FA treatment recorded the lower significant values of plasma cholesterol, triglyceride and LDL, but, the birds fed FA recorded the higher significant value of plasma HDL, plasma hemoglobin, globulin fractions(α, β, and γ-globulin), transferrin and tri-iodothyronine concentration levels compared with birds fed with or without FA. In conclusion, in-ovo injection of Fe-Meth. or FeNPs and fed the diet fortified with FA were sufficient to improve broiler performance or physiological response in broiler chickens.
Inside Brokers

We identify the stockbroker each corporate insider trades through, and show that analysts and mutual fund managers affiliated with such "inside brokers'' retain a substantial information advantage on the insider's firm, even after these trades are disclosed. Affiliated analysts issue 10-20% more accurate earnings forecasts, and affiliated funds trade the insider's stock much more profitably than their peers, following insider trades through their brokerage. Our results challenge the prevalent perception that information asymmetry arising from insider trading is acute only before trade disclosure, and suggest that brokers facilitating these trades are in a unique position to exploit such an asymmetry.
Selection Bias and the Cross-Section of Expected Returns

We propose an estimate of expected returns that accounts for selective anomaly submission and publication, and apply our adjustment to a broad cross-section of anomaly hedge portfolio returns. Selection bias accounts for a modest 10 to 15% of the typical in-sample return. This small bias is due to fact that the dispersion of in-sample returns is nearly twice as large as the typical standard error, indicating a significant amount of variation in true returns. The bias is much smaller than the out-of-sample decline in anomaly returns, showing that that investors learn about mispricing from academic research. Estimations on simulated data show that our bias adjustment is robust. ∗This paper originated from a conversation with Frank Schorfheide. We thank David McLean and seminar participants at the Federal Reserve Board and Georgetown for helpful comments. We are grateful to Robert Novy-Marx and Mihail Velikov for making their data available. The views expressed herein are those of the authors and do not necessarily reflect the position of the Board of Governors of the Federal Reserve or the Federal Reserve System.