Miracle-dz/UniFAR-FTUs huggingface dataset:
Referral to medical oncology: a crucial step in the treatment of older patients with stage III colon cancer.

PURPOSE Adjuvant chemotherapy for stage III colon cancer produces a substantial survival benefit, but many older patients do not receive chemotherapy. This study examines factors associated with medical oncology consultation and evaluates the impact of such consultation on chemotherapy use. PATIENTS AND METHODS We used the Surveillance Epidemiology and End Results-Medicare linked database and identified 7,569 patients, aged 66-99, with stage III colon cancer diagnosed from 1992-1999. Modified Poisson regression was used to assess the relative risk for seeing a medical oncologist and for receiving chemotherapy as a function of individual characteristics. RESULTS 78.08% of patients saw a medical oncologist within 6 months of diagnosis. Patients who were female, white, married, had low comorbidity scores, were diagnosed in more recent years, or had four or more positive lymph nodes were more likely to see a medical oncologist. Patients seeing a medical oncologist were 10 times more likely to receive chemotherapy (odds ratio, 9.98; 95% confidence interval, 8.21-12.14), after controlling for demographic and tumor characteristics. Chemotherapy use increased over time, but was substantially lower among older, black, and unmarried patients. CONCLUSIONS Referral to medical oncology is one of the most important factors associated with receipt of chemotherapy among older patients with stage III colon cancer. Comorbidity decreases the likelihood of receiving chemotherapy, but its effect is the same for those who see a medical oncologist and all patients combined. Ensuring that high-risk patients are referred to medical oncology is a crucial step in quality care for patients with colon cancer.
Role of quercetin in cadmium-induced oxidative stress, neuronal damage, and apoptosis in rats

The present study was carried out to evaluate the neuroprotective effect of quercetin (QE) in protecting the cadmium (Cd)-induced neuronal injury in frontal cortex of rats. A total of 30 adult male Sprague-Dawley rats were randomly divided into three groups of 10 animals each: control, Cd treated and Cd treated with QE. The Cd-treated group was injected subcutaneously with cadmium chloride (CdCl2) dissolved in saline at a dose of 2 ml/kg/day for 30 days, resulting in a dosage of 1 mg/kg Cd. The rats in QE-treated groups were given QE (15 mg/kg body weight) once a day intraperitoneally starting 2 days prior to Cd injection, during the study period. Rats were sacrificed at the end of the study and the frontal cortex tissues were removed for biochemical and histopathological investigation. To date, there is no available information on the effect of QE on neuronal injury after Cd exposure. Rats intoxicated with Cd for 30 days, significantly increased tissue malondialdehyde (MDA) levels and significantly decreased enzymatic antioxidants superoxide dismutase, glutathione peroxidase and catalase in the frontal cortex tissue. Administration of QE with Cd significantly diminished the levels of MDA and significantly elevated the levels of enzymatic antioxidants in the frontal cortex tissue. The histopathological studies in the brain of rats also supported that QE markedly reduced the Cd-induced histopathological changes and well preserved the normal histological architecture of the frontal cortex tissue. The caspase-3 immunopositivity was increased in degenerating neurons of the Cd group. Treatment with QE markedly reduced the immunoreactivity of degenerating neurons. In conclusion, the results of the current study suggest that QE may be beneficial in combating the Cd-induced neurotoxicity in the brain of rats. We believe that further preclinical research into the utility of QE may indicate its usefulness as a potential treatment for neurodegeneration after Cd exposure in rats.
Reproductive epigenetics

Epigenetics refers to covalent modifications of DNA and core histones that regulate gene activity without altering DNA sequence. To date, the best‐characterized DNA modification associated with the modulation of gene activity is methylation of cytosine residues within CpG dinucleotides. Human disorders associated with epigenetic abnormalities include rare imprinting diseases, molar pregnancies, and childhood cancers. Germ cell development and early embryo development are critical times when epigenetic patterns are initiated or maintained. This review focuses on the epigenetic modification DNA methylation and discusses recent progress that has been made in understanding when and how epigenetic patterns are differentially established in the male and female germlines, the mouse, and human disorders associated with abnormalities in epigenetic programming in germ cells and early embryos, as well as genetic and other modulators (e.g. nutrition and drugs) of reproductive epigenetic events.
Global meta-analysis reveals no net change in local-scale plant biodiversity over time

Significance A major advance of the last 20 y at the interface of biological, environmental, and conservation sciences has been the demonstration that plant biodiversity positively influences ecosystem function. Linking these results to applied conservation efforts hinges on the assumption that biodiversity is actually declining at the local scale at which diversity–function relationships are strongest. Our compilation and analysis of a global database of >16,000 repeat survey vegetation plots from habitats across the globe directly contradict this assumption. We find no general tendency for local-scale plant species diversity to decline over the last century, calling into question the widespread use of ecosystem function experiments to argue for the importance of biodiversity conservation in nature. Global biodiversity is in decline. This is of concern for aesthetic and ethical reasons, but possibly also for practical reasons, as suggested by experimental studies, mostly with plants, showing that biodiversity reductions in small study plots can lead to compromised ecosystem function. However, inferring that ecosystem functions will decline due to biodiversity loss in the real world rests on the untested assumption that such loss is actually occurring at these small scales in nature. Using a global database of 168 published studies and >16,000 nonexperimental, local-scale vegetation plots, we show that mean temporal change in species diversity over periods of 5–261 y is not different from zero, with increases at least as likely as declines over time. Sites influenced primarily by plant species’ invasions showed a tendency for declines in species richness, whereas sites undergoing postdisturbance succession showed increases in richness over time. Other distinctions among studies had little influence on temporal richness trends. Although maximizing diversity is likely important for maintaining ecosystem function in intensely managed systems such as restored grasslands or tree plantations, the clear lack of any general tendency for plant biodiversity to decline at small scales in nature directly contradicts the key assumption linking experimental results to ecosystem function as a motivation for biodiversity conservation in nature. How often real world changes in the diversity and composition of plant communities at the local scale cause ecosystem function to deteriorate, or actually to improve, remains unknown and is in critical need of further study.
Skeletal muscle metabolic recovery following submaximal exercise in chronic heart failure is limited more by O(2) delivery than O(2) utilization.

CHF (chronic heart failure) is associated with a prolonged recovery of skeletal muscle energy stores following submaximal exercise, limiting the ability to perform repetitive daily activities.However, the pathophysiological background of this impairment is not well established. The aim of the present study was to investigate whether muscle metabolic recovery following submaximal exercise in patients with CHF is limited by O2 delivery or O2 utilization. A total of 13 stable CHF patients (New York Heart Association classes II-III) and eight healthy subjects, matched for age and BMI (body mass index), were included. All subjects performed repetitive submaximal dynamic single leg extensions in the supine position. Post-exercise PCr (phosphocreatine) resynthesis was assessed by 31P-MRS (magnetic resonance spectroscopy). NIRS (near-IR spectroscopy) was applied simultaneously, using the rate of decrease in HHb (deoxygenated haemoglobin) as an index of post-exercise muscle re-oxygenation. As expected, PCr recovery was slower in CHF patients than in control subjects (time constant, 47+/-10 compared with 35+/-12 s respectively; P=0.04). HHb recovery kinetics were also prolonged in CHF patients (mean response time, 74+/-41 compared with 44+/-17 s respectively; P=0.04). In the patient group, HHb recovery kinetics were slower than PCr recovery kinetics (P=0.02), whereas no difference existed in the control group(P=0.32). In conclusion, prolonged metabolic recovery in CHF patients is associated with an even slower muscle tissue re-oxygenation, indicating a lower O(2) delivery relative to metabolic demands. Therefore we postulate that the impaired ability to perform repetitive daily activities in these patients depends more on a reduced muscle blood flow than on limitations in O(2) utilization.
Carbohydrate attenuates perceived exertion during intermittent exercise and recovery.

PURPOSE The purpose of this study was to examine the effect of carbohydrate supplementation on differentiated and undifferentiated ratings of perceived exertion (RPE) during prolonged intermittent exercise and recovery. METHODS Twelve male subjects cycled for 2.0 h at 64% Wmax and 73% V O2peak with 3-min rest intervals interspersed every 10 min (2.6 h of total exercise time, including rest intervals) with placebo (P) or carbohydrate (C) beverages. RPE was assessed during the last minute of each 10-min exercise interval and then every 30 s during the 3-min recovery period. RESULTS The pattern of change in RPE over time was significantly different between C and P ingestion (P < 0.05), with attenuated RPE responses found for both overall body (O) and legs (L). A significant main effect was found for recovery RPE-O between C and P ingestion (P < 0.05), with attenuated RPE responses found in the later part of the 2-h run. C relative to P ingestion was associated with higher respiratory exchange ratios and plasma levels of glucose and with lower levels of plasma cortisol. CONCLUSIONS These data indicate that carbohydrate supplementation attenuates perceived exertion during prolonged intermittent exercise and recovery.
Bovine Viral Diarrhea Virus: Prevention of Persistent Fetal Infection by a Combination of Two Mutations Affecting Erns RNase and Npro Protease

ABSTRACT Different genetically engineered mutants of bovine viral diarrhea virus (BVDV) were analyzed for the ability to establish infection in the fetuses of pregnant heifers. The virus mutants exhibited either a deletion of the overwhelming part of the genomic region coding for the N-terminal protease Npro, a deletion of codon 349, which abrogates the RNase activity of the structural glycoprotein Erns, or a combination of both mutations. Two months after infection of pregnant cattle with wild-type virus or either of the single mutants, the majority of the fetuses contained virus or were aborted or found dead in the uterus. In contrast, the double mutant was not recovered from fetal tissues after a similar challenge, and no dead fetuses were found. This result was verified with a nonrelated BVDV containing similar mutations. After intrauterine challenge with wild-type virus, mutated viruses, and cytopathogenic BVDV, all viruses could be detected in fetal tissue after 5, 7, and 14 days. Type 1 interferon (IFN) could be detected in fetal serum after challenge, except with wild-type noncytopathogenic BVDV. On days 7 and 14 after challenge, the largest quantities of IFN in fetal serum were induced by the Npro and RNase-negative double mutant virus. The longer duration of fetal infection with the double mutant resulted in abortion. Therefore, for the first time, we have demonstrated the essential role of both Npro and Erns RNase in blocking interferon induction and establishing persistent infection by a pestivirus in the natural host.
The salivary glands and salivary bladder of the nine‐banded armadillo

Histochemical studies of armadillo salivary glands reveal mucous acini as the predominant secretory unit of the submaxillary and parotid glands. The acidic carbohydrate moiety of the salivary mucin is mostly sialic acid since Vibrio cholera neuraminidase (sialidase) markedly reduces the alcian blue reaction in the acinar cells. Morphologically, the acini of the submaxillary gland resemble the long mucous tubules of carnivore zygomatic glands whereas the parotid gland corresponds more closely to the seromucous classification. In the submaxillary gland specialized afferent ducts terminate in a storage organ called the salivary bladder. Contents of the bladder consist of a highly viscous sialomucin plus varying amounts of acidophilic material which is negative to the periodic acid‐Schiff and alcian blue reactions. The bladder itself is composed of a wall made up of cuboidal epithelium, skeletal muscle and connective tissue and it is emptied by means of a single efferent duct which leads to the oral cavity. Parotid gland striated ducts are characterized by simple columnar epithelium containing considerable amounts of glycogen in the basal two‐thirds of the cells.
Cueing training in the home improves gait-related mobility in Parkinson’s disease: the RESCUE trial

Objectives: Gait and mobility problems are difficult to treat in people with Parkinson’s disease. The Rehabilitation in Parkinson’s Disease: Strategies for Cueing (RESCUE) trial investigated the effects of a home physiotherapy programme based on rhythmical cueing on gait and gait-related activity. Methods: A single-blind randomised crossover trial was set up, including 153 patients with Parkinson’s disease aged between 41 and 80 years and in Hoehn and Yahr stage II–IV. Subjects allocated to early intervention (n = 76) received a 3-week home cueing programme using a prototype cueing device, followed by 3 weeks without training. Patients allocated to late intervention (n = 77) underwent the same intervention and control period in reverse order. After the initial 6 weeks, both groups had a 6-week follow-up without training. Posture and gait scores (PG scores) measured at 3, 6 and 12 weeks by blinded testers were the primary outcome measure. Secondary outcomes included specific measures on gait, freezing and balance, functional activities, quality of life and carer strain. Results: Small but significant improvements were found after intervention of 4.2% on the PG scores (p = 0.005). Severity of freezing was reduced by 5.5% in freezers only (p = 0.007). Gait speed (p = 0.005), step length (p<0.001) and timed balance tests (p = 0.003) improved in the full cohort. Other than a greater confidence to carry out functional activities (Falls Efficacy Scale, p = 0.04), no carry-over effects were observed in functional and quality of life domains. Effects of intervention had reduced considerably at 6-week follow-up. Conclusions: Cueing training in the home has specific effects on gait, freezing and balance. The decline in effectiveness of intervention effects underscores the need for permanent cueing devices and follow-up treatment. Cueing training may be a useful therapeutic adjunct to the overall management of gait disturbance in Parkinson’s disease.
Absence of Metabolic Cross-correction in Tay-Sachs Cells

We have investigated the ability of a receptor-mediated gene transfer strategy (cross-correction) to restore ganglioside metabolism in fibroblasts from Tay-Sachs (TS) patientsin vitro. TS disease is a GM2 gangliosidosis attributed to the deficiency of the lysosomal enzyme β-hexosaminidase A (HexA) (β-N-acetylhexosaminidase, EC 3.2.1.52). The hypothesis is that transduced cells overexpressing and secreting large amounts of the enzyme would lead to a measurable activity in defective cells via a secretion-recapture mechanism. We transduced NIH3T3 murine fibroblasts with the LαHexTN retroviral vector carrying the cDNA encoding for the human Hex α-subunit. The Hex activity in the medium from transduced cells was approximately 10-fold higher (up to 75 milliunits) than observed in non-transduced cells. TS cells were cultured for 72 h in the presence of the cell medium derived from the transduced NIH3T3 cells, and they were analyzed for the presence and catalytic activity of the enzyme. Although TS cells were able to efficiently uptake a large amount of the soluble enzyme, the enzyme failed to reach the lysosomes in a sufficient quantity to hydrolyze the GM2 ganglioside to GM3 ganglioside. Thus, our results showed that delivery of the therapeutic HexA was not sufficient to correct the phenotype of TS cells.
Renal Glomerular Fibrosis in Two Pigs

Massive deposition of collagen fibrils was found in the renal glomeruli of two pigs. The affected pigs were a 6-month-old female hybrid pig with systemic mycobacteriosis and a retired sow showing azotemia. Microscopically, various amounts of a homogeneous eosinophilic substance were deposited within the expanded mesangium of almost all renal glomeruli in both cases. The deposit was also seen occasionally on the glomerular capillary walls in the sow. Capillary lumens were occluded in the glomerular segments with heavy deposition. Obsolescent glomeruli were often surrounded by lymphoid cells. The deposited substance was Congo red negative and stained deep blue with Heidenhain's azan staining. Immunohistochemical evaluation revealed that the major component of the homogeneous substance was type-Ill collagen. Electron microscopic examination showed that the deposits were masses of fibrils of variable length, width, and shape. The fibrils had transverse bands with a periodicity of approximately 60 nm, consistent with collagen fibrils. These glomerular changes were identical to those of collagenofibrotic glomerulonephropathy that has recently been described as a new glomerular disease in humans. The glomerular lesion may be the result of unusual production of type-III collagen by mesangial cells.
The risk of minor depression before age 65: results from a community survey

Synopsis Data from a general population survey of psychiatric disorder in Camberwell were used to calculate the risk of a CATEGO-defined depressive episode before the age of 65, using a modification of Strömgren's method. Current depression was defined as cases within the relevant categories of the CATEGO program and at threshold level or above on the Index of Definition (Wing et al. 1978). A past history of depression was elicited using key symptoms such as persistent tearfulness and depressed mood, already enquired after in the course of the PSE, to identify potential episodes, followed by questions to determine accessory symptoms, duration, and degree of social impairment. Clinical judgement was then used to decide whether the disturbance constituted a significant depressive episode. Risk under one set of assumptions was 46 % for men and 72 % for women. Using another method based on (untenably) conservative assumptions, it became 16 % and 30 % respectively. The status and implications of these high values are discussed, particularly for genetic studies.
Effect of host populations on the intensity of ticks and the prevalence of tick-borne pathogens: how to interpret the results of deer exclosure experiments

SUMMARY Deer are important blood hosts for feeding Ixodes ricinus ticks but they do not support transmission of many tick-borne pathogens, so acting as dead-end transmission hosts. Mathematical models show their role as tick amplifiers, but also suggest that they dilute pathogen transmission, thus reducing infection prevalence. Empirical evidence for this is conflicting: experimental plots with deer removal (i.e. deer exclosures) show that the effect depends on the size of the exclosure. Here we present simulations of dynamic models that take into account different tick stages, and several host species (e.g. rodents) that may move to and from deer exclosures; models were calibrated with respect to Ixodes ricinus ticks and tick-borne encephalitis (TBE) in Trentino (northern Italy). Results show that in small exclosures, the density of rodent-feeding ticks may be higher inside than outside, whereas in large exclosures, a reduction of such tick density may be reached. Similarly, TBE prevalence in rodents decreases in large exclosures and may be slightly higher in small exclosures than outside them. The density of infected questing nymphs inside small exclosures can be much higher, in our numerical example almost twice as large as that outside, leading to potential TBE infection risk hotspots.
Accounting Conservatism, Information Uncertainty and Analysts' Forecasts

This study examines how accounting conservatism may affect the information environment of analysts' earnings forecasts, taking into account the interaction between unconditional and conditional conservatism. Unconditional conservatism preempts conditional conservatism in the later period and reduces the uncertainty in loss recognition associated with bad news. Through a simple analyst forecast model, I demonstrate that: 1) unconditional conservatism is negatively correlated with analysts' forecast errors for good news or mild bad news firms, but positively correlated with analysts' forecast errors for extreme bad news firms; and 2) unconditional conservatism reduces the overall uncertainty in analysts' forecasts. The empirical results are consistent with the predictions. Moreover, the evidence shows that the impact of unconditional conservatism on analysts' forecasts is greater for early forecasts, when the information uncertainty is high, than for late forecasts.
Multi-Channel Sequential Search with Application to Piracy

This paper presents a multi-channel search model, where each channel consists of multiple firms that are ex ante homogeneous to consumers. Consumers, nevertheless, ex ante can tell channels apart in the following aspects: search costs, product quality, product availability and price distributions. We first analyze the channel selection problem and show that a consumer’s optimal channel selection at any stage of the search is independent of found prices. We further show that the optimal channel choice can be determined using each channel’s reservation price and consumer valuation. We then apply this model to study the competition between legitimate and pirated products. One immediate result is reducing piracy services has no impact on consumers’ decision to pirate. When pirated products pose a threat, legitimate firms may respond by giving up low search cost consumers. This leads to the surprising result that piracy threat may induce firms to increase their product prices.