Miracle-dz/UniFAR-FTUs huggingface dataset:
Value of Histopathology in Predicting Microsatellite Instability in Hereditary Nonpolyposis Colorectal Cancer and Sporadic Colorectal Cancer

Identification of colorectal carcinomas with high levels of DNA microsatellite instability (MSI-H) is important because of the suggested prognostic and therapeutic significance associated with MSI. The role of histology in identifying MSI-H colorectal carcinomas has been suggested by some studies but not confirmed by others. Furthermore, previous studies assumed that hereditary nonpolyposis colorectal cancer (HNPCC)-associated MSI-H tumors and sporadic MSI-H tumors have similar histology. This assumption, however, has been challenged by more recent studies. In this report, we first analyzed the value of various histologic features in predicting MSI-H in a series of 218 colorectal carcinomas containing mixed HNPCC and sporadic cases [77 tumors (35%) were MSI-H by polymerase chain reaction (PCR) method]. Then, we evaluated the various histologic features comparatively in two groups extracted from the 218 cases. Group A was composed of 84 tumors from 82 patients obtained based on a strong family history (HNPCC/HNPCC-like group) (male to female ratio, 42:40; age range, 23–80 years, median, 53.5 years). Thirty-one of the 84 tumors (41.7%) were MSI-H by PCR, and all 31cases were HNPCC by Amsterdam criteria. Group B was composed of 109 patients with no family history of colorectal cancer or HNPCC-associated cancer, obtained from surgical clinics (sporadic group) (male to female ratio, 65:69; age range, 31–84 years, median, 65 years). Thirty-five of the 109 tumors (32.1%) were MSI-H by PCR. Our results showed that, overall, poor tumor differentiation, medullary type, mucinous type, signet-ring cell component, histologic heterogeneity, and increased tumor-infiltrating lymphocytes (TILs) were features more commonly seen in MSI-H tumors than in non-MSI-H tumors. Comparative analyses showed that the overall TIL count was significantly higher in HNPCC/HNPCC-like group, and mucinous type appeared to be more frequent in HNPCC MSI-H tumors than in sporadic MSI-H tumors. However, there was no significant difference in the odds ratio for predicting MSI-H status for any of the analyzed histologic features between HNPCC/HNPCC-like group and sporadic group, indicating that differences between HNPCC and sporadic MSI-H tumors did not significantly impact on the informative value of histology in predicting MSI in the two different clinical settings. TIL counts followed by histologic heterogeneity provided the greatest sensitivity and specificity in predicting MSI status in both HNPCC/HNPCC-like and sporadic cases. Using a stepwise logistic regression model, a formula was generated that could be used to calculate the probability of a colorectal carcinoma being MSI-H based on morphologic features.
Role of AIF in cardiac apoptosis in hypertrophic cardiomyocytes from Dahl salt-sensitive rats.

AIMS The caspases are thought to be central mediators of the apoptotic program, but recent data indicate that apoptosis may also be mediated by caspase-independent mechanisms such as apoptosis-inducing factor (AIF). The role of AIF-induced apoptosis in heart, however, is currently not well understood. The aim of this study was to investigate the presence of and conditions for AIF-induced cardiac apoptosis in vitro. METHODS AND RESULTS Hypertrophic cardiomyocyte (H-CM) cultures were prepared from the hearts of Dahl salt-sensitive rats fed a high salt diet. Apoptotic stimulation induced by hypoxia/reoxygenation or staurosporine (1 microM) enhanced AIF release in H-CMs compared with non-hypertrophic cardiomyocytes (N-CMs). Caspase inhibition using zVAD.fmk (25 microM) or overexpression of CrmA using recombinant adenovirus only partially protected N-CMs from apoptosis (63 +/- 0.93%) and provided no significant protection against apoptosis in hypertrophic cells (23 +/- 1.03%). On the other hand, poly-ADP-ribose polymerase inhibition using 4-AN (20 microM) during apoptotic stimulation blocked the release of AIF from mitochondria and significantly improved cell viability in hypertrophied cardiomyocytes (74 +/- 1.18%). CONCLUSION A caspase-dependent, apoptotic pathway is important for N-CM death, whereas a caspase-independent, AIF-mediated pathway plays a critical role in H-CMs.
Absolute Pitch Twin Study and Segregation Analysis

Absolute pitch is a rare pitch-naming ability with unknown etiology. Some scientists maintain that its manifestation depends solely on environmental factors, while others suggest that genetic factors contribute to it. We sought to further investigate the hypothesis that genetic factors support the acquisition of absolute pitch and to better elucidate the inheritance pattern of this trait. To this end, we conducted a twin study and a segregation analysis using data collected from a large population of absolute pitch possessors. The casewise concordance rate of 14 monozygotic twin pairs, 78.6%, was significantly different from that of 31 dizygotic twin pairs, 45.2%, assuming single ascertainment (x2 = 5.57, 1 df, p = .018), supporting a role for genetics in the development of absolute pitch. Segregation analysis of 1463 families, assuming single ascertainment, produced a segregation ratio pD = . 089 with SEpD = 0.006. Unlike an earlier segregation analysis on a small number of absolute pitch probands from musically educated families, our study indicates that absolute pitch is not inherited in a simple Mendelian fashion. Based on these data, absolute pitch is likely genetically heterogeneous, with environmental, epigenetic, and stochastic factors also perhaps contributing to its genesis. These findings are in agreement with the results of our recent linkage analysis.
Linear Energy Transfer-Dependent Change in Rice Gene Expression Profile after Heavy-Ion Beam Irradiation

A heavy-ion beam has been recognized as an effective mutagen for plant breeding and applied to the many kinds of crops including rice. In contrast with X-ray or γ-ray, the heavy-ion beam is characterized by a high linear energy transfer (LET). LET is an important factor affecting several aspects of the irradiation effect, e.g. cell survival and mutation frequency, making the heavy-ion beam an effective mutagen. To study the mechanisms behind LET-dependent effects, expression profiling was performed after heavy-ion beam irradiation of imbibed rice seeds. Array-based experiments at three time points (0.5, 1, 2 h after the irradiation) revealed that the number of up- or down-regulated genes was highest 2 h after irradiation. Array-based experiments with four different LETs at 2 h after irradiation identified LET-independent regulated genes that were up/down-regulated regardless of the value of LET; LET–dependent regulated genes, whose expression level increased with the rise of LET value, were also identified. Gene ontology (GO) analysis of LET-independent up-regulated genes showed that some GO terms were commonly enriched, both 2 hours and 3 weeks after irradiation. GO terms enriched in LET-dependent regulated genes implied that some factor regulates genes that have kinase activity or DNA-binding activity in cooperation with the ATM gene. Of the LET-dependent up-regulated genes, OsPARP3 and OsPCNA were identified, which are involved in DNA repair pathways. This indicates that the Ku-independent alternative non-homologous end-joining pathway may contribute to repairing complex DNA legions induced by high-LET irradiation. These findings may clarify various LET-dependent responses in rice.
Evidence that α2‐antiplasmin becomes covalently ligated to plasma fibrinogen in the circulation: a new role for plasma factor XIII in fibrinolysis regulation

Summary. Background: Plasma alpha2‐antiplasmin (α2AP) is a rapid and effective inhibitor of the fibrinolytic enzyme plasmin. Congenital α2AP deficiency results in a severe hemorrhagic disorder due to accelerated fibrinolysis. It is well established that in the presence of thrombin‐activated factor XIII (FXIIIa), α2AP becomes covalently ligated to the distal α chains of fibrin or fibrinogen at lysine 303 (two potential sites per molecule). Some time ago we showed that α2AP is covalently linked to plasma fibrinogen . That singular observation led to our hypothesis that native plasma factor XIII (FXIII), which is known to catalyze covalent cross‐linking of fibrinogen in the presence of calcium ions, can also incorporate α2AP into fibrinogen in the circulation. Results and Conclusions: We now provide evidence that FXIII incorporates I125‐labelled α2AP into the Aα‐chain sites on fibrinogen or fibrin. We also measured the content of α2AP in isolated plasma fibrinogen fractions by ELISA and found that substantial amounts were present (1.2–1.8 moles per mole fibrinogen). We propose that α2AP becomes ligated to fibrinogen while in the circulation through the action of FXIII, and that its immediate presence in plasma fibrinogen contributes to regulation of in vivo fibrinolysis.
Botrytis cinerea isolates collected from grapes present different requirements for conidia germination

Botrytis cinerea presents high variability in several biological traits, which can be explained by the high degree of genotypic diversity among isolates. Because this genetic variability might be related to phenotypic differences the requirements for conidia germination of three natural isolates (G1, G5 and G11) obtained from grapes and belonging to the same genetic group were analyzed. The results showed that contact with a solid surface was a common requisite for conidia germination of the isolates but they differed in their nutritional requirements to germinate. Isolate G11 was able to germinate in the absence of a carbon or nitrogen source. G1 and G5 required the presence of a carbon source such as glucose, fructose or sucrose. In G11 and G5 isolates a much higher rate of germination was obtained in the presence of sucrose. It was shown with a pharmacological approach that the cAMP stimulated the germination only in those isolates requiring a carbon source. Conidia germination of G1 and G5 was inhibited by EGTA, a calcium chelator. Isolate G11 germinated in the presence of this compound. On the other hand the germination of three B. cinerea isolates required protein synthesis and did not require RNA synthesis. To explain the ability of isolate G11 to germinate in water the content of total and reducing sugars, mannitol/l-arabitol, trehalose, and proteins in the nongerminated conidia of the three isolates was compared. The isolates presented similar amounts of total and reducing sugars. In the three isolates the amount of mannitol/l-arabitol was higher than that of trehalose. In isolate G11 total protein content was twice higher than in the other isolates.
A Preoperative Prognostic Score for Resected Pancreatic and Periampullary Neuroendocrine Tumours

Background/Aims: To identify potential preoperative prognostic factors in resected pancreatic and periampullary neuroendocrine tumours. Methods: Clinico-pathological data for 54 consecutive patients with pancreatic or periampullary neuroendocrine tumours referred to our institution over a 10-year period were identified from a prospective database. Results: 34 patients underwent pancreatic resection (12 males, 22 females; median age 54 (IQR 44–71) years). There was a single 30-day mortality (3%). Nodal status (log rank, p = 0.652), microscopic resection margin involvement (p = 0.549) and tumour size (p = 0.122) failed to exhibit any prognostic value. Only the presence of malignant tumour characteristics was associated with poorer overall survival (p = 0.008). Analysis of preoperative parameters showed that age >60 years (p = 0.056), platelet-lymphocyte ratio >300 (p = 0.008), alkaline phosphatase levels >125 U/l (p = 0.042) and alanine aminotransferase >35 U/l (p = 0.016) were adverse prognostic factors. A risk stratification score was generated where each adverse preoperative parameter was allocated a score of 1. A cumulative score of ≤1 was defined as low risk, while a score of ≥2 was defined as high risk. Median overall survival in the high-risk group was 10.4 months, while the median survival in the low-risk group was >60 months (p < 0.001). Conclusion: Significant prognostic information can be gained from routine preoperative biochemistry and haematology results in resected pancreatic and periampullary neuroendocrine tumours. These findings merit further evaluation in a larger patient cohort.
Nitrogen recycling or nitrogen conservation in an alga-invertebrate symbiosis?

When corals and allied animals are deprived of their symbiotic algae, the ammonium content in their tissues rises. This is commonly interpreted as evidence for nitrogen recycling (i.e. algal assimilation of animal waste ammonium into amino acids that are released back to the animal), but it can also be explained as nitrogen conservation by the animal (i.e. reduced net ammonium production in response to the receipt of algal photosynthetic carbon). This study discriminated between these interpretations in two ways. First, the increased ammonium concentration in the sea anemone Aiptasia pulchella, caused by darkness or depletion of the alga Symbiodinium, was partially or completely reversed by supplementing the medium with organic carbon compounds (e.g. -ketoglutarate). Second, the activity of the ammonium-assimilating enzyme glutamine synthetase and the concentration of protein amino acids in the free amino acid pool of the animal, which were depressed by darkness and algal depletion, were restored by exogenous carbon compounds. It is concluded that organic carbon, whether derived from algal photosynthate or exogenously, promotes the animal's capacity for ammonium assimilation and reduces ammonium production from amino acid degradation. These processes contribute to nitrogen conservation in the animal, but they confound the interpretation of various studies on nitrogen recycling by symbiotic algae.
Longitudinal relations between temperament traits and behavioral syndromes in middle childhood.

OBJECTIVE This study tested Graham and Stevenson's 1987 hypothesis specifying links between EAS (emotionality-activity-sociability) temperament traits and behavioral syndromes of depression, hyperactivity, and delinquency in an unselected sample of 164 children in infancy and early childhood. METHOD Mothers completed the Colorado Child Temperament Inventory. Each mother also used the Child Behavior Checklist (CBCL) to report on her child's behavior problems after the child's completion of first grade. Scores on three CBCL scales, anxiety/depression, attention problems, and delinquent behavior, were examined in relation to the EAS traits. RESULTS For boys, high emotionality in infancy and early childhood was associated with high scores on both the anxiety/depression and attention problem scales. For girls, both high emotionality and low sociability predicted high scores on the anxiety/depression scale. There were no associations between EAS traits and attention problems for girls. There was little evidence for links between EAS traits and delinquent behavior for either boys or girls. CONCLUSIONS The results are discussed with respect to temperamental traits as risk factors for the emergence of behavior problems in childhood.
Peritransplant tolerance induction with anti-CD3-immunotoxin: a matter of proinflammatory cytokine control.

BACKGROUND Tolerance is gaining momentum as an approach to reduce lifelong immunosuppressive therapy while improving transplant longevity. Anti-CD3 immunotoxin (IT), FN18-CRM9, has potential to induce tolerance owing to its exceptional ability to deplete sessile lymph node T cells. However, if initiated at the time of transplantation, alpha-CD3-IT alone elicits a proinflammatory cytokine response, precluding establishment of tolerance. METHODS Four groups of rhesus monkeys received kidney allografts and immunosuppression. Three groups received alpha-CD3-IT alone or alpha-CD3-IT supplemented with 15-deoxyspergualin (DSG) and/or methylprednisolone (MP). One group received alpha-CD3-monoclonal antibody with DSG and MP. Cytokines were measured by enzyme-linked immunosorbent assay. RESULTS Supplementing peritransplant alpha-CD3-IT treatment with a brief course of DSG and MP promoted rejection-free kidney allograft acceptance in 75% of macaques followed for up to 550 days. Among those given alpha-CD3-IT alone or with MP, none were long-term survivors. Tolerance developed after alpha-CD3-IT, DSG, and MP treatment, but not when the unconjugated a-CD3 monoclonal antibody was substituted for IT. Systemic production of proinflammatory cytokines interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha induced after peritransplant alpha-CD3-IT was prevented only in animals given DSG. Despite high levels of interleukin (IL)-12 in the first month after transplant, tolerant recipients exhibited IL-12 resistance, as evidenced by baseline plasma levels of IFN-gamma but elevated IL-4. DSG was shown to inhibit IL-12-driven IFN-gamma production by a mechanism associated with inhibition of nuclear factor kappa-B. CONCLUSIONS In this model, peritransplant induction of tolerance is promoted by efficient elimination of sessile lymph node T cells and control of the proinflammatory IFN-gamma response by a mechanism that appears to involve resistance to IL-12.
Neuralized functions cell autonomously to regulate Drosophila sense organ development

Neurogenic genes, including Notch and Delta, are thought to play important roles in regulating cell–cell interactions required for Drosophila sense organ development. To define the requirement of the neurogenic gene neuralized (neu) in this process, two independent neu alleles were used to generate mutant clones. We find that neu is required for determination of cell fates within the proneural cluster and that cells mutant for neu autonomously adopt neural fates when adjacent to wild‐type cells. Furthermore, neu is required within the sense organ lineage to determine the fates of daughter cells and accessory cells. To gain insight into the mechanism by which neu functions, we used the GAL4/UAS system to express wild‐type and epitope‐tagged neu constructs. We show that Neu protein is localized primarily at the plasma membrane. We propose that the function of neu in sense organ development is to affect the ability of cells to receive Notch‐Delta signals and thus modulate neurogenic activity that allows for the specification of non‐neuronal cell fates in the sense organ.
Dietary Fiber, Glycemic Load, and Risk of NIDDM in Men

OBJECTIVE Intake of carbohydrates that provide a large glycemic response has been hypothesized to increase the risk of NIDDM, whereas dietary fiber is suspected to reduce incidence. These hypotheses have not been evaluated prospectively. RESEARCH DESIGN AND METHODS We examined the relationship between diet and risk of NIDDM in a cohort of 42,759 men without NIDDM or cardiovascular disease, who were 40–75 years of age in 1986. Diet was assessed at baseline by a validated semiquantitative food frequency questionnaire. During 6-years of follow-up, 523 incident cases of NIDDM were documented. RESULTS The dietary glycemic index (an indicator of carbohydrate's ability to raise blood glucose levels) was positively associated with risk of NIDDM after adjustment for age, BMI, smoking, physical activity, family history of diabetes, alcohol consumption, cereal fiber, and total energy intake. Comparing the highest and lowest quintiles, the relative risk (RR) of NIDDM was 1.37 (95% CI, 1.02–1.83, P trend = 0.03). Cereal fiber was inversely associated with risk of NIDDM (RR = 0.70; 95% CI, 0.51–0.96, P trend = 0.007; for > 8.1 g/day vs. < 3.2 g/day). The combination of a high glycemic load and a low cereal fiber intake further increased the risk of NIDDM (RR = 2.17, 95% CI, 1.04–4.54) when compared with a low glycemic load and high cereal fiber intake. CONCLUSIONS These findings support the hypothesis that diets with a high glycemic load and a low cereal fiber content increase risk of NIDDM in men. Further, they suggest that grains should be consumed in a minimally refined form to reduce the incidence of NIDDM.
Facial Video-Based Photoplethysmography to Detect HRV at Rest

Abstract Our aim is to demonstrate the usefulness of photoplethysmography (PPG) for analyzing heart rate variability (HRV) using a standard 5-min test at rest with paced breathing, comparing the results with real RR intervals and testing supine and sitting positions. Simultaneous recordings of R–R intervals were conducted with a Polar system and a non-contact PPG, based on facial video recording on 20 individuals. Data analysis and editing were performed with individually designated software for each instrument. Agreement on HRV parameters was assessed with concordance correlations, effect size from ANOVA and Bland and Altman plots. For supine position, differences between video and Polar systems showed a small effect size in most HRV parameters. For sitting position, these differences showed a moderate effect size in most HRV parameters. A new procedure, based on the pixels that contained more heart beat information, is proposed for improving the signal-to-noise ratio in the PPG video signal. Results were acceptable in both positions but better in the supine position. Our approach could be relevant for applications that require monitoring of stress or cardio-respiratory health, such as effort/recuperation states in sports.
Recovery and screening for antibiotic susceptibility of potential bacterial pathogens from the oral cavity of shark species involved in attacks on humans in Recife, Brazil.

The number of incidents involving sharks and humans at beaches in Recife, on the north-eastern Brazilian coast, is among the highest worldwide. In addition, wound infections in survivors are common; but the nature and risk of the aetiological agents is unknown. In the present study, 81 potential bacterial pathogens were identified in the oral cavity of sharks involved in attacks in Recife, and were subjected to antibiotic susceptibility tests using the standardized disc-diffusion method. The majority were enterobacteria such as Enterobacter spp. , Citrobacter spp. , Proteus spp. , Providencia alcalifaciens, Escherichia coli, Moellerella wisconcensis and Leclercia adecarboxylata. Other Gram-negative bacteria included Vibrio spp. , Burkholderia cepacia, Acinetobacter spp. and Pseudomonas spp. In addition, coagulase-positive and coagulase-negative Staphylococcus spp. , Enterococcus spp. and Micrococcus spp. were identified, besides Streptococcus spp. from the viridans group. Resistance was especially found in the Proteus mirabilis and Citrobacter freundii, and ranged from 4 to 6 antibiotics out of the 13 tested. Gentamicin and vancomycin were the most effective against Gram-positive cocci strains, whereas levofloxacin was fully inhibitory against Gram-positive and Gram-negative bacteria. These data are discussed in light of a retrospective evaluation of the medical records of three shark victims treated at Restauração Hospital in Recife.