Miracle-dz/UniFAR-FTUs huggingface dataset:
Functional Interaction of H2AX, NBS1, and p53 in ATM-Dependent DNA Damage Responses and Tumor Suppression

ABSTRACT Ataxia-telangiectasia (A-T) mutated (ATM) kinase signals all three cell cycle checkpoints after DNA double-stranded break (DSB) damage. H2AX, NBS1, and p53 are substrates of ATM kinase and are involved in ATM-dependent DNA damage responses. We show here that H2AX is dispensable for the activation of ATM and p53 responses after DNA DSB damage. Therefore, H2AX functions primarily as a downstream mediator of ATM functions in the parallel pathway of p53. NBS1 appears to function both as an activator of ATM and as an adapter to mediate ATM activities after DNA DSB damage. Phosphorylation of ATM and H2AX induced by DNA DSB damage is normal in NBS1 mutant/mutant (NBS1m/m) mice that express an N-terminally truncated NBS1 at lower levels. Therefore, the pleiotropic A-T-related systemic and cellular defects observed in NBS1m/m mice are due to the disruption of the adapter function of NBS1 in mediating ATM activities. While H2AX is required for the irradiation-induced focus formation of NBS1, our findings indicate that NBS1 and H2AX have distinct roles in DNA damage responses. ATM-dependent phosphorylation of p53 and p53 responses are largely normal in NBS1m/m mice after DNA DSB damage, and p53 deficiency greatly facilitates tumorigenesis in NBS1m/m mice. Therefore, NBS1, H2AX, and p53 play synergistic roles in ATM-dependent DNA damage responses and tumor suppression.
PHANTOM LIMBS: COMPARISON WITH NORMAL SUBJECTS

Received, November 19, 2002. Accepted, July 23, 2003. OBJECTIVE: To demonstrate that amputees performing “virtual” movements of their amputated limb activate cortical areas previously devoted to their missing limb, we studied amputees with functional magnetic resonance imaging (fMRI) and positron emission tomographic (PET) scans and compared the results with those of normal volunteers performing imaginary movements during fMRI acquisitions. METHODS: Ten amputees (age range, 33–92 yr; average age, 49 yr; six men and four women; eight upper-limb and two lower-limb amputations) able to move their phantom limb at will were studied by fMRI (all patients) and PET scan (seven patients). The time between amputation and fMRI and PET studies ranged from 1 to 27 years (average, 13 yr). Patients were asked to perform virtual movements of the amputated limb and normal movements of the contralateral normal limb according to the functional images acquisition procedure. Movements of the stump were also used to differentiate stump cortical areas from virtual movement-activated areas. Ten right-handed volunteers, ageand sexmatched to the amputees, were also studied by fMRI. All volunteers were asked to perform four tasks during their fMRI study: imaginary movements of their right arm (1 task) and foot (1 task) and real movements of their left arm (1 task) and foot (1 task). RESULTS: In amputees, virtual movements of the missing limbs produced contralateral primary sensorimotor cortex activation on both fMRI and PET scans. These activation areas, different from the stump activation areas, were similar in location to contralateral normal limb-activated areas. Quantitatively, in two amputees who claimed to be able to perform both slow and fast virtual movements, regional cerebral blood flow measured by PET scan in the precentral gyrus increased significantly during fast movements in comparison with slow virtual movements. In normal subjects, significant differences between real versus imaginary fMRI activations were found (for both foot and hand movements); imaginary right hand and foot tasks activated primarily the contralateral supplementary motor areas, with no significant activation detected in the contralateral precentral or postcentral gyri. CONCLUSION: Primary sensorimotor cortical areas can be activated by phantom-limb movements and thus can be considered functional for several years or decades after amputation. In this study, we found that the location of the activation of these areas is comparable to that of activations produced by normal movements in control subjects or in amputees.
Kidney as a major clearance organ for recombinant human interleukin-1 receptor antagonist.

This study was designed to provide information on the tissue distribution and elimination of recombinant human interleukin-1 receptor antagonist (rhIL-1ra) in rats. Following intravenous (iv) bolus administration of metabolically labeled [35S]rhIL-1ra alone or together with unlabeled rhIL-1ra, biodistribution of [35S]rhIL-1ra in the early phase as well as at steady state was investigated. The renal elimination of rhIL-1ra at steady state was also studied. In the early phase biodistribution study, 11, 9, 6, and 2% of the dose was distributed to the kidney, liver, gut, and lung, respectively. Additional rhIL-1ra was found in muscle (43%) and plasma (26%). The time profiles of [35S]rhIL-1ra in the kidney and liver were analyzed by integration plots to determine the early-phase distribution clearance of [35S]rhIL-1ra. The distribution clearance of [35]rhIL-1ra per gram of kidney was five times greater than that of the liver. When expressed as clearance per organ, total liver clearance and total renal clearance were comparable, together accounting for approximately 20% of plasma clearance in the early phase. The distribution clearances of [35S]rhIL-1ra in these tissues (liver and kidney) were not affected by coadministration of excess unlabeled rhIL-1ra (5 mg/rat), indicating that clearance occurs via a mechanism having a high capacity for rhIL-1ra. The steady-state biodistribution of rhIL-1ra was also studied to examine the accumulation of rhIL-1ra in the tissues. The tissue-to-plasma concentration ratios at steady state were similar to the corresponding extracellular spaces in the tissues investigated except the kidney, where the ratio was 4.10. (ABSTRACT TRUNCATED AT 250 WORDS)
Cue Interaction Effects in Causal Judgement: An Interpretation in Terms of the Evidential Evaluation Model

In judging the extent to which a cue causes an outcome, judgement can be affected by information about other cues that are correlated with the one being judged. These cue interaction effects have usually been interpreted in terms of associative learning processes. I propose that a different model of causal judgement, the evidential evaluation model, offers a viable alternative interpretation of cue interaction phenomena. Under the evidential evaluation model, instances of contingency information are interpreted as evidence, which is confirmatory, disconfirmatory, or irrelevant for the cue being judged. When two cues co-occur in a set of instances the evidential value of the instances for one of them is determined by three factors: the proportion of confirming instances in the set; disambiguation value, which concerns the relation between the set of information and prior beliefs about the co-occurring cue; and confirmation value, which concerns the relation between the set of information and prior beliefs about the cue being judged. Any previous judgement of the cue is then modified in the light of these. It is shown that this model can account for all the cue interaction phenomena that have been investigated in studies of human causal judgement. The model also generates novel predictions, and the results of three experiments give support to these predictions. It is also shown that several other current models of causal judgement fail to predict a key result from Experiment 3.
ncidence , treatment , and case-fatality of non-traumatic subarachnoid aemorrhage in the Netherlands

Background: Non-traumatic subarachnoid haemorrhage (SAH) is a devastating disorder and in the majority of cases it is caused by rupture of an intracranial aneurysm. No actual data are available on the incidence of non-traumatic SAH and aneursymal SAH (aSAH) in the Netherlands and little is known about treatment patterns of aSAH. Our purpose was therefore to assess the incidence, treatment patterns, and case-fatality of non-traumatic (a)SAH within the Dutch general population. Methods: Two population based data sources were used for this retrospective cohort study. One was the nationwide hospital discharge registry (National Medical Registration, LMR). Cases were patients hospitalized for SAH (ICD-9-code 430) in 2001–2005. The second source was the Integrated Primary Care Information (IPCI) database, a medical record database allowing for case validation. Cases were patients with validated non-traumatic (a)SAH in 1996–2006. Incidence, treatment, and case-fatality were assessed. Results: The incidence rate (IR) of non-traumatic SAH was 7.12 per 100,000 PY (95%CI: 6.94–7.31) and increased with age. The IR of aSAH was 3.78 (95%CI: 2.98–4.72). Women had a twofold increased risk of non-traumatic SAH; this difference appeared after the fourth decade. Non-traumatic SAH fatality was 30% (95%CI: 29–31%). Of aSAH patients 64% (95%CI: 53–74%) were treated with a clipping procedure, and 26% (95%CI: 17–37%) with coiling. ic SAH ries. Conclusion: Non-traumat are similar to other count
Knowledge, attitude and practices of Qatari patients with type 2 diabetes mellitus

Objectives Patient compliance with their medications and their ability for self‐management in type 2 diabetes mellitus (T2DM) is a growing cause of concern to healthcare providers. Knowledge about diabetes, attitude towards the condition and time management with respect to the condition (practice), collectively known as KAP, are known to affect compliance and play an important part in diabetes management. We aimed to describe the knowledge, attitude, practice and psychological status of adult Qatari patients with T2DM, and to explore the interaction between these and other patient‐related factors which could impact on the ability of the patients to manage their diabetes and to achieve desirable health outcomes.
Interferon-Dependent Engagement of Eukaryotic Initiation Factor 4B via S6 Kinase (S6K)- and Ribosomal Protein S6K-Mediated Signals

ABSTRACT Although the roles of Jak-Stat pathways in type I and II interferon (IFN)-dependent transcriptional regulation are well established, the precise mechanisms of mRNA translation for IFN-sensitive genes remain to be defined. We examined the effects of IFNs on the phosphorylation/activation of eukaryotic translation initiation factor 4B (eIF4B). Our data show that eIF4B is phosphorylated on Ser422 during treatment of sensitive cells with alpha IFN (IFN-α) or IFN-γ. Such phosphorylation is regulated, in a cell type-specific manner, by either the p70 S6 kinase (S6K) or the p90 ribosomal protein S6K (RSK) and results in enhanced interaction of the protein with eIF3A (p170/eIF3A) and increased associated ATPase activity. Our data also demonstrate that IFN-inducible eIF4B activity and IFN-stimulated gene 15 protein (ISG15) or IFN-γ-inducible chemokine CXCL-10 protein expression are diminished in S6k1/S6k2 double-knockout mouse embryonic fibroblasts. In addition, IFN-α-inducible ISG15 protein expression is blocked by eIF4B or eIF3A knockdown, establishing a requirement for these proteins in mRNA translation/protein expression by IFNs. Importantly, the generation of IFN-dependent growth inhibitory effects on primitive leukemic progenitors is dependent on activation of the S6K/eIF4B or RSK/eIF4B pathway. Taken together, our findings establish critical roles for S6K and RSK in the induction of IFN-dependent biological effects and define a key regulatory role for eIF4B as a common mediator and integrator of IFN-generated signals from these kinases.
Psychological Evaluation after Cardiac Transplantation: The Integration of Different Criteria

Background: The psychological evaluation of patients undergoing cardiac transplantation is currently based on DSM-IV criteria. An alternative diagnostic and conceptual framework has been proposed by an international group of psychosomatic investigators. The aim of this study was to compare these new criteria (Diagnostic Criteria for Psychosomatic Research, DCPR) with DSM-IV in a population where a high prevalence of psychological problems is expected (heart-transplanted patients). Method: 129 consecutive patients who underwent heart transplant surgery were assessed according to DSM-IV and DCPR criteria. Results: The results showed a higher number of diagnoses made using the DCPR than with the use of the DSM-IV. At least one DCPR diagnosis was found in 85 (66%) patients, whereas at least one DSM diagnosis was present in 23 (18%) patients. The number of DCPR diagnoses was almost the triple of DSM criteria. While patients who were given a DSM diagnosis frequently had additional DCPR diagnoses, many patients with DCPR criteria did not fulfill any DSM criteria. Four DCPR syndromes appeared to be particularly frequent: demoralization, type A behavior, irritable mood and alexithymia. Conclusions: The joint use of DSM and DCPR criteria was found to improve the identification of psychological factors which could result in a worsening of quality of life in heart-transplanted patients.
Cyclin D1 positive diffuse large B-cell lymphoma is a post-germinal center-type lymphoma without alterations in the CCND1 gene locus

The aims of this study were to analyze the incidence and morphology of cyclin D1+ DLBCL and cases of Richter transformation (RT), and to elucidate possible molecular mechanisms of cyclin D1 overexpression. Seventy-two cases of de novo DLBCL and 12 cases of RT were included in this study. Cyclin D1 positivity was found in 10/66 (15%) cases of unselected de novo DLBCL and in 2/11 (18%) cases of RT. Seven independently identified cases of cyclin D1+ DLBCL, including one RT, were added to the study. Centroblastic morphology was found in 17/19 (89%) cases of cyclin D1+, most with a post-germinal center phenotype (CD10−, BCL6+, MUM1+). No alterations in the CCND1 gene indicative for a translocation t(11;14) were identified by FISH. Analysis of the MYC locus yielded gene copy alterations in five cases and no disruption of the gene locus in any case, suggesting an alternative mechanism of cyclin D1 deregulation.
Characterization of a Tandem Repeat Polymorphism in Legionella pneumophila and Its Use for Genotyping

ABSTRACT We have analyzed the variability of minisatellite sequences (also called variable-number tandem repeats [VNTRs]) in the genome of Legionella pneumophila. Based upon the genome sequence of the Philadelphia-1 strain (serogroup 1), 25 minisatellites were selected and their polymorphisms were analyzed by PCR with the DNA of serogroup 1 to 14 reference strains. For 22 markers, a PCR product of the expected size was found with the DNA of the Philadelphia-1 strain. Most of these markers did not amplify the DNA of other Legionella species or other bacteria used as controls. A polymorphism was observed for seven markers among the L. pneumophila strains tested. To check whether these markers could be used to compare strains of L. pneumophila, we analyzed two groups of isolates from clinical and environmental samples which had been independently genotyped by other methods. The results showed that, for the isolates in these two sets of samples, VNTR typing is as informative as pulsed-field gel electrophoresis for comparison of strains. Sequencing of one minisatellite from 14 reference strains was performed. Comparison of the sequences allowed a classification and confirmed the existence of subspecies of L. pneumophila. We also tested the usefulness of one very polymorphic marker as a tool for the rapid screening of colonies grown from water samples. This allowed the rapid identification of the L. pneumophila colonies and gave a first hint as to the presence of several strains in a single sample.
Cytoreductive surgery and hyperthermic intrathoracic chemotherapy perfusion for malignant pleural tumours: perioperative management and clinical experience.

OBJECTIVES A combination of cytoreductive surgery and hyperthermic intrathoracic chemotherapy perfusion (HITHOC) was performed for the treatment of primary and secondary pleural malignancies. We describe the perioperative management and our clinical experience. METHODS Between September 2008 and August 2011, eight patients with pleural manifestation of thymoma (Masaoka stage IVa) and eight patients with malignant pleural mesothelioma (MPM) were prospectively enrolled. Postoperative morbidity, recurrence and survival rates were analysed. RESULTS All the patients received multimodality therapy, including chemotherapy, radiation and surgical resection (pleurectomy/decortication) followed by the HITHOC procedure. Chemotherapy perfusion was performed with cisplatin (100-150 mg/m(2)) at 42°C for 1 h. Severe chemotherapy-related complications were not observed. Reoperation was necessary in two patients. There was no 30-day mortality. The median stay on the intensive care unit was 1 day, and the median duration of hospitalization was 15 days. Pleural recurrence of thymoma was evident in one thymoma patient 6 months after HITHOC. At mean follow-up of 22 months, seven thymoma patients (7/8; 88%) are alive without recurrence. Tumour progression was present in six mesothelioma patients (6/8; 75%). Four patients (50%) with MPM are alive, including two with no evidence of mesothelioma, and the median survival is 18 months. CONCLUSIONS Cytoreductive surgery in combination with HITHOC can be performed with acceptable morbidity and mortality rates in selected patients. Patients should be evaluated by an interdisciplinary team to determine their eligibility for this therapeutic alternative. Early clinical results may encourage the use of this surgical option to provide better local tumour control in a multimodality treatment setting.
Meta‐Analysis of Prospective Studies of Red Meat Consumption and Colorectal Cancer

The relationship between red meat consumption and colorectal cancer (CRC) has been the subject of scientific debate. Thus, to estimate the summary association between red meat intake and CRC and to examine heterogeneity, a meta‐analysis of prospective studies was conducted. Thirty‐four prospective studies of red meat and CRC were identified, of which, 24 represented independent non‐overlapping study populations. Random effects meta‐analysis models were utilized to calculate summary relative risk estimates (SRREs) for high vs. low intake and dose‐response relationships. In the high vs. low intake meta‐analysis of all studies, the SRRE was 1.13 (95% CI: 1.04–1.23), although there was significant heterogeneity (p = 0.016). Summary associations were modified by tumor site and gender. The SRREs for colon cancer and rectal cancer were 1.11 (95% CI: 1.03–1.19) and 1.19 (95% CI: 0.97–1.46), respectively. The SRREs among men and women were 1.21 (95% CI: 1.04–1.42) and 1.01 (95% CI: 0.87–1.17), respectively. The available epidemiologic data are not sufficient to support an independent positive association between red meat intake and CRC. This conclusion is based upon summary associations that are weak in magnitude, heterogeneity between available studies, inconsistent patterns of associations across the sub‐groups analyses, and the likely influence of confounding by other dietary and lifestyle factors.
Intestinal Microbiota as Novel Biomarkers of Prior Radiation Exposure

There is an urgent need for rapid, accurate, and sensitive diagnostic platforms to confirm exposure to radiation and estimate the dose absorbed by individuals subjected to acts of radiological terrorism, nuclear power plant accidents, or nuclear warfare. Clinical symptoms and physical dosimeters, even when available, do not provide adequate diagnostic information to triage and treat life-threatening radiation injuries. We hypothesized that intestinal microbiota act as novel biomarkers of prior radiation exposure. Adult male Wistar rats (n = 5/group) received single or multiple fraction total-body irradiation of 10.0 Gy and 18.0 Gy, respectively. Fresh fecal pellets were obtained from each rat prior to (day 0) and at days 4, 11, and 21 post-irradiation. Fecal microbiota composition was determined using microarray and quantitative PCR (polymerase chain reaction) analyses. The radiation exposure biomarkers consisted of increased 16S rRNA levels of 12 members of the Bacteroidales, Lactobacillaceae, and Streptococcaceae after radiation exposure, unchanged levels of 98 Clostridiaceae and Peptostreptococcaceae, and decreased levels of 47 separate Clostridiaceae members; these biomarkers are present in human and rat feces. As a result of the ubiquity of these biomarkers, this biomarker technique is non-invasive; microbiota provide a sustained level of reporting signals that are increased several-fold following exposure to radiation, and intestinal microbiota that are unaffected by radiation serve as internal controls. We conclude that intestinal microbiota serve as novel biomarkers of prior radiation exposure, and may be able to complement conventional chromosome aberrational analysis to significantly enhance biological dose assessments.
Evidence of new species of Haematoloechus (Platyhelminthes: Digenea) using partial cox1 sequences

Background and aims. Haematoloechus, digeneans parasites of amphibians, is a species-rich genus with more than 50 species around the globe. Establishing an accurate taxonomy for this group has been difficult due to high intraspecific variability. Nuclear DNA sequences have given independent information about species validity and phylogeny of the group. Materials and methods. In this paper, I test the performance of partial sequences of the mitochondrial cytochrome c oxidase subunit I (cox1) gene in the differentiation of recognized species of the genus and in the detection of potential new taxa. Samples from 13 nominal species were sequenced, plus four samples that could not be assigned to any described species based on morphology. Results. Parsimony analysis of the amplified 360 bp fragment resulted in six most parsimonious trees showing the same grouping of samples, differing in the samples' arrangement within those groups. All 13 species were recovered on the trees, and five potential new species are shown. Conclusion. Additional sampling and sequencing is necessary to support this hypothesis, but with this preliminary information the search for diagnostic characters that allow the description of the new taxa is less difficult.
A Compare-Aggregate Model with Dynamic-Clip Attention for Answer Selection

Answer selection for question answering is a challenging task, since it requires effective capture of the complex semantic relations between questions and answers. Previous remarkable approaches mainly adopt general Compare-Aggregate framework that performs word-level comparison and aggregation. In this paper, unlike previous Compare-Aggregate models which utilize the traditional attention mechanism to generate corresponding word-level vector before comparison, we propose a novel attention mechanism named Dynamic-Clip Attention which is directly integrated into the Compare-Aggregate framework. Dynamic-Clip Attention focuses on filtering out noise in attention matrix, in order to better mine the semantic relevance of word-level vectors. At the same time, different from previous Compare-Aggregate works which treat answer selection task as a pointwise classification problem, we propose a listwise ranking approach to model this task to learn the relative order of candidate answers. Experiments on TrecQA and WikiQA datasets show that our proposed model achieves the state-of-the-art performance.