Miracle-dz/UniFAR-FTUs huggingface dataset:
Prognostic implications of basophil differentiation in chronic myeloid leukemia

Basophilia has been reported to indicate an accelerated phase of chronic myeloid leukemia (CML), heralding a poor prognosis. We have studied 47 patients with chronic‐phase CML by basophil growth and differentiation assays in vitro, demonstrating an association between basophil growth index (BGI) and clinical time to blast crisis as well as overall survival. In addition to confirming an association between positive BGI and phase of CML in a larger group of patients, a positive BGI predicted death or blast crisis within 2 years' study of chronic phase CML (p<0.01), with a sensitivity of 78%, specificity, 81%; the positive predictive value of a positive test, 64%; and a negative predictive value of a negative test, 89%. The survival experience of the 22 evaluable patients with chronic‐phase CML and a positive BGI was significantly worse than the survival of the 19 patients with a negative BGI (p<0.0001). At 1, 2, and 3 years the proportion of surviving patients with a positive BGI was 0.64, 0.32, and 0.23, respectively, compared with 1.00, 0.90, and 0.79 for those with a negative BGI. The median survival of chronic phase CML patients with a positive test at diagnosis (n = 14) was 27 months versus 54 months for those with a negative diagnosis (n = 14) (p<0.05). These findings emphasize the prognostic utility of basophil growth assays in CML and suggest a molecular relationship between leukemic transformation and basophil lineage expression.
Benzodiazepine Binding Studies on Living Cells: Application of Small Ligands for Fluorescence Correlation Spectroscopy

Abstract We demonstrate the applicability of fluorescence correlation spectroscopy (FCS) for receptor binding studies using low molecular weight ligands on membranes of living nerve cells. The binding of benzodiazepine Ro 7 1986/602 (Ndesdiethylfluorazepam), labeled with the fluorophore Alexa 532, the benzodiazepine receptor was analyzed quantitatively at the membrane of single rat hippocampal neurons. The values obtained for the dissociation constant Kd = (9.9±1.9) nM and the rate constant for ligandreceptor dissociation kdiss = (1.28±0.08)10- 3 s 1 show that there is a specific and high affinity interaction between the dyelabeled ligand (RoAlexa) and the receptor site. The binding was saturated at approx. 100 and displacement of 10 nM RoAlexa, with a 1000- excess of midazolam, showed a nonspecific binding of 7 10%. Additionally, two populations of the benzodiazepine receptor that differed in their lateral mobility were detected in the membrane of rat neurons. The diffusion coefficients for these two populations [Dbound1 = (1.32±0.26) m2/s; Dbound2 = (2.63±0.63)10- 2 m2/s] related to binding sites, which shows a monoexponential decay in a timedependent dissociation of ligandreceptor complex.
miRNA profiling identifies deregulated miRNAs associated with osteosarcoma development and time to metastasis in two large cohorts

Osteosarcoma (OS) is an aggressive bone tumor primarily affecting children and adolescents. The etiology of OS is not fully understood. Thus, there is a great need to obtain a better understanding of OS development and progression. Alterations in miRNA expression contribute to the required molecular alterations for neoplastic initiation and progression. This study is the first to investigate miRNA expression in OS in a large discovery and validation cohort comprising a total of 101 OS samples. We established the signature of altered miRNA expression in OS by profiling the expression level of 752 miRNAs in 23 OS samples using sensitive LNA‐enhanced qPCR assays. The identified miRNA expression changes were correlated with gene expression in the same samples. Furthermore, miRNA expression changes were validated in a second independent cohort consisting of 78 OS samples. Analysis of 752 miRNAs in the discovery cohort led to the identification of 33 deregulated miRNAs in OS. Twenty‐nine miRNAs were validated with statistical significance in the second cohort comprising 78 OS samples. miRNA/mRNA targets were determined, and 361 genes with an inverse expression of the target miRNA were identified. Both the miRNAs and the identified target genes were associated with multiple pathways related to cancer as well as bone cell biology, thereby correlating the deregulated miRNAs with OS tumorigenesis. An analysis of the prognostic value of the 29 miRNAs identified miR‐221/miR‐222 to be significantly associated with time to metastasis in both cohorts. This study contributes to a more profound understanding of OS tumorigenesis, by substantiating the importance of miRNA deregulation. We have identified and validated 29 deregulated miRNAs in the – to our knowledge – largest discovery and validation cohorts used so far for miRNA analyses in OS. Two of the miRNAs showed a promising potential as prognostic biomarkers for the aggressiveness of OS.
Impact of HIV-1 Infection on VH3 Gene Repertoire of Naive Human B Cells1

B cells of the largest Ig variable heavy chain gene (VH) family, VH3, are reportedly decreased in patients with late stage HIV-1 disease. This deficit may contribute to their impaired responses to infections and vaccines. We confirmed that the VH3 family was underrepresented in serum IgM proteins, with a 45% decrease in patients with advanced HIV-1 disease. However, the proportion of VH3 within VH(1–6) IgM mRNA from peripheral B cells did not differ from that of control subjects (mean ± SD, 57.1 ± 9.7 vs 61.1 ± 8.7%). Similarly, within VH(1–6) IgD mRNA, which even more closely represents the unstimulated naive repertoire, the relative expression of VH3 mRNA was comparable in the two groups. Moreover, the frequency of individual genes within the VH3 family for IgD, particularly genes which encode putative HIV-1 gp120 binding sites, also was normal in HIV-1-infected patients. However, VH3 family expression for IgG mRNA was significantly decreased (17%) and VH4 IgG was increased (33%) relative to other VH families in advanced HIV-1-infected patients. Thus, the changes in VH family expression were more readily apparent in previously activated IgG “memory” B cell populations and, likely, in cells actively producing IgM rather than in resting naive cells. The presence of a relatively normal naive VH3 IgM and IgD mRNA repertoire in resting cells supports the prospect that with proper stimulation, particularly in conjunction with effective antiviral therapy, vigorous humoral immune responses to infections and vaccines may be elicited in this high-risk population.
eHealth Literacy Interventions for Older Adults: A Systematic Review of the Literature

Background eHealth resources offer new opportunities for older adults to access health information online, connect with others with shared health interests, and manage their health. However, older adults often lack sufficient eHealth literacy to maximize their benefit from these resources. Objective This review evaluates the research design, methods, and findings of eHealth literacy interventions for older adults. Methods A systematic review of peer-reviewed research articles from 28 databases in 9 fields was carried out in January 2013. Four rounds of screening of articles in these databases resulted in a final sample of 23 articles. Results Findings indicated a significant gap in the literature for eHealth literacy interventions evaluating health outcomes as the outcome of interest, a lack of theory-based interventions, and few studies applied high-quality research design. Conclusions Our findings emphasize the need for researchers to develop and assess theory-based interventions applying high-quality research design in eHealth literacy interventions targeting the older population.
Isolated Weakness of Radial-side Fingers Due to a Small Cortical Infarction

중추 신경계 병터에 의해 손가락의 일부에만 위약감이 발생하는 것을 거짓 말초 마비라고 한다. 두 명의 환자가 뇌의 국소 병터에 의해 요측에 국한된 특정 손가락의 위약감을 가지고 내원하였다. 51세 여자 환자는 갑자기 발생한 왼쪽 검지와 중지의 위약감으로 내원하였으며, 뇌 자기공명영상검사에서 오른쪽 중심앞이랑에 뇌경색이 관찰되었다. 67세 남자환자는 갑자기 오른쪽 엄지와 검지로 위약감이 발생하였으며, 뇌 자기공명영상검사에서 왼쪽 중심앞이랑에 뇌경색이 관찰되었다. 【Predominant involvement of a particular group of fingers due to a central nervous system lesion has been described as pseudoperipheral palsy. Two patients visited our hospital with isolated weakness of a particular group of fingers due to small cortical infarctions. A 51-year-old woman suddenly developed weakness in her left index and middle fingers. The brain MRI showed a small infarct in the right frontal cortex. A 67-year-old man was sudden difficulty using his chopsticks and had weakness in his right thumb and index finger. The brain MRI showed a small infarct in the left precentral cortex. 】
In Vitro Culture of Mesenchymal Lineage Cells Established from the Colonial Tunicate Botryllus primigenus

Abstract Body trunks were isolated from juvenile zooids of the Japanese colonial tunicate Botryllus primigenus and cultured in vitro to establish tissue-specific cell lines. Epidermal cells from some explants spread and formed a flat sheet consisting of vacuolated cells. They then dissociated into single cells, and their growth stopped within two weeks. Continuously proliferating cells were established from four explants. After the 20th implantation, nuclear and mitochondrial DNAs were extracted from these cells. The nucleotide sequences of proliferating cell nuclear antigen (PCNA) and mitochondrial large ribosomal RNA (mtlrRNA) completely matched the PCNA and mtlrRNA taken from living colonies of B. primigenus; this shows that the four independently proliferating cells were indeed of the Botryllus origin. One cell line (Bp0306E10) comprised round-shaped cells with a diameter of 8–10 μm. These cells have been cultured in vitro with a doubling time of approximately 24 hours since June, 2003. The BrdU labeling index was approximately 2%. Monoclonal antibodies raised against the cultured cells recognized a 28 kDa polypeptide and stained free mesenchymal cells in vivo. G418-resistant subclonal cells could be established by introducing a tunicate retrotransposon loaded with the neomycin resistance gene into the cells by electroporation. This study is the first to succeed in producing a sustainable cell culture of Botryllus.
How can a child be a mother? Discourse on teenage pregnancy in a Brazilian favela

Contemporary research reveals the body as a privileged place for social memory and resistance, especially among those people who are politically and economically marginalized. But what might the body signify within the context of teenage pregnancy in conditions of chronic poverty? To explore these issues, semi‐structured interviews were conducted with 21 boys and 17 girls living in a favela in São Paulo, Brazil. In their responses, young people drew a clear distinction between sex and parenthood. If sex sometimes holds negative connotations, maternity and the physical appearance of pregnancy increases social status. Young people's representations of teenage pregnancy do not portray it as a social or health problem. Instead, they understand it as a consequence of the desire to be visible and active in social life. Findings highlight the importance of investigating the relationship between young people's sexuality and the social imaginary, particularly in conditions of social inequality and suffering.
Career examination through a LEAP framework: liberal arts graduates' perceptions of employment skills in the workforce

The purpose of this mixed methods sequential exploratory study was to develop an understanding of the ways in which graduates of liberal arts programs recognize, make meaning of, and apply the competencies developed as an undergraduate within the workplace. In the first quantitative phase of the study, the research questions addressed the association among liberal arts graduates’ perceived importance, academic preparation, and assessment of value attributed by employers of eight critical skills in the workplace and any differences based on participants’ academic domain. The data were collected via a self-developed web-based survey (N=328) sent to graduates of six institutions representing four different Carnegie classifications. The overall response rate was 9.4%. A chi-square analysis in conjunction with the Holm-Bonferroni procedure yielded a statistically significant relationship in five of nine academic domain relationships. A post-hoc contingency table analysis further revealed statistically significant results between academic vii domain and perception value categories. In the second qualitative phase, eight case studies, consisting of graduates of liberal arts programs from four Carnegie classifications and four academic domains, delved deeper into the results from the first phase. Four themes emerged during the withinand cross-case analysis related to participants’ perceptions of the use of critical skills in the workplace: (1) Personal accountability to the job, (2) workplace dynamics among coworkers, clients, and supervisors, (3) self-awareness of what is important in the workplace, and (4) employer support of the liberal arts in the workplace. The final phase of the study integrated the quantitative results and qualitative findings to determine broad-scale outcomes of the study. Based on the overall analysis, the study provides policy implications and recommendations related to practical skill development within liberal arts
Mindful Economics: The Production, Consumption, and Value of Beliefs

In the economic models of old, agents had backward-looking expectations, arising from simple extrapolation or error-correction rules. Then came the rational-expectations revolution in macroeconomics, and in microeconomics the spread and increasing refinements of modern game theory. Agents were now highly sophisticated information processors, who could not be systematically fooled. This approach reigned for several decades until the pendulum swung back with the rise of behavioral economics and its emphasis on “heuristics and biases” (as in Tversky and Kahneman 1974). Overconfidence, confirmation bias, distorted probability weights, and a host of other “wired-in” cognitive mistakes are now common assumptions in many areas of economics. Over the last decade or so, the pendulum has started to swing again toward some form of adaptiveness, or at least implicit purposefulness, in human cognition. In this paper, we provide a perspective into the main ideas and findings emerging from the growing literature on motivated beliefs and reasoning. This perspective emphasizes that beliefs often fulfill important psychological and functional needs of the individual. Economically relevant examples include confidence in ones’ abilities, moral self-esteem, hope and anxiety reduction, social identity, political ideology and religious faith. People thus hold certain beliefs in part because
Multiagents to separating handwritten connected digits

This paper addresses an important and vital problem within the general area of character recognition, namely separating connected digits in handwritten numerals. The basic idea is employing multiagents to handle this problem. Our approach is mainly based on detecting the deepest-top valley and the highest-bottom hill, with one agent dedicated to each. The former agent decides on candidate cut-point as the closest feature point to the center of the deepest top-valley, if any. On the other hand, the other agent argues candidate cut-point as the closest feature point to the center of the highest bottom-hill, if any. After each of the two agents applies its own rules and reports a candidate cut-point, the two agents negotiate to agree on the actual cut-point. It may happen that both agents come to the negotiation with the same candidate cut-point. However, in general, each agent may find a different candidate cut-point and they negotiate a compromise on the actual cut-point, which may be neither of the two already proposed cut-points. A degree of confidence in each candidate cut-point influences the negotiation process. Experiments conducted so far are promising and successful. The obtained results are very encouraging with a success factor of 97.8%. Finally, none of the two agents alone achieved a close success rate.
Horizontal Transfer of Antimicrobial Resistance by Extended-Spectrum β Lactamase-Producing Enterobacteriaceae

Background: The purpose of this work was to study the acquisition of new antibiotic-resistant genes carried by extended spectrum β–lactamase (ESBL)-producing Enterobacteriaceae via horizontal transfer to understand their rampant spread in the hospitals and in the community. Materials and Methods: A retrospective analysis of 120 ESBL screen-positive isolates of Escherichia coli and Klebsiella pneumoniae, which were subjected to antimicrobial susceptibility testing, was carried out. The Double Disc Synergy Test (DDST) and Inhibitor-Potentiation Disc Diffusion Test (IPDD) were employed for confirmation of ESBL activity. The transferability of the associated antibiotic resistance for amoxicillin, amikacin, gentamicin, cefotaxime and ceftriaxone was elucidated by intra- and intergenus conjugation in Escherichia coli under laboratory as well as under simulated environmental conditions. Transformation experiments using plasmids isolated by alkaline lysis method were performed to study the transferability of resistance genes in Klebsiella pneumoniae isolates. Results: ESBL production was indicated in 20% each of the Escherichia coli and Klebsiella pneumoniae isolates. All the ESBL isolates showed co- resistance to various other groups of antibiotics, including 3GC antibiotics, though all the isolates were sensitive to both the carbapenems tested. Conjugation-mediated transfer of resistance under laboratory as well as environmental conditions at a frequency of 3–4 × 10-5, and transformation-mediated dissemination of cefotaxime and gentamicin resistance shed light on the propensity of ESBL producers for horizontal transfer. Conclusions: The transfer of resistant markers indicated availability of a large pool of resistance genes in the hospital setting as well as in the environment, facilitating long-term persistence of organisms.
Ligand-mediated Induction of Thymidylate Synthase Occurs by Enzyme Stabilization

Thymidylate synthase (TS) is indispensable in thede novo synthesis of dTMP. As such, it has been an important target at which anti-neoplastic drugs are directed. The fluoropyrimidines 5-fluorouracil and 5-fluoro-2′-deoxyuridine are cytotoxic as a consequence of inhibition of TS by the metabolite 5-fluoro-2′-deoxyuridine 5′-monophosphate (FdUMP). This inhibition occurs through formation of a stable ternary complex among the enzyme, the nucleotide analog, and the co-substrateN 5,N 10-methylenetetrahydrofolate. Numerous studies have shown that cellular concentrations of TS undergo about a 2–4-fold induction following treatment with TS inhibitors. An extensive body of in vitro studies has led to the proposal that this induction occurs because of relief of the translational repression brought on by the binding of TS to its own mRNA. In the current study, we have tested several predictions of this autoregulatory translation model. In contrast to expectations, we find that fluoropyrimidines do not cause a change in the extent of ribosome binding to TS mRNA. Furthermore, mutations within the mRNA that abolish its ability to bind TS have no effect on the induction. Finally, enzyme turnover measurements show that the induction is associated with an increase in the stability of the TS polypeptide. Our results, in total, indicate that enzyme stabilization, rather than translational derepression, is the primary mechanism of TS induction by fluoropyrimidines and call into question the general applicability of the autoregulatory translation model.
Clinical Characteristics of Familial vs. Sporadic non-Hodgkin lymphoma in Patients Diagnosed at The Mayo Clinic (1986 – 2000)

There are few data on the clinical characteristics of familial vs. sporadic non-Hodgkin lymphoma (NHL). Using the NHL registry at the Mayo Clinic, we compared age of diagnosis, gender, tumor site and histologic subtype between patients with sporadic and familial NHL. In 2001, we identified all new cases of adult NHL diagnosed between 1986 and 2000 in the Mayo Clinic NHL database (n = 2289) and mailed out a family history questionnaire to all living patients with a current address (n = 1043). Each NHL patient was categorized according to their self-report of leukemia or lymphoma in first-degree (1 degree) relatives. We received complete FH information on 740 patients (71%). Age at diagnosis of NHL ranged from 18-88 years (mean = 59 years) and 53% of our cases were male. First-degree FH of lymphoma was reported by 43 patients (6%), 1 degree FH of leukemia by 27 patients (4%) and 1 degree FH of both in 4 (1%). There was a nonstatistically significant later age at diagnosis for cases with any family history of lymphoma or leukemia (mean age = 61.3 and 61.7 years, respectively) vs. no family history (59.0 years) (P = 0.58). The male to female ratio for those with a FH of leukemia (ratio = 2.9) was higher compared to those with FH lymphoma (0.95) or no FH (1.1) (P = 0.08). No differences were apparent between 1 degree FH and site of NHL (nodal vs. extranodal) (P = 0.53). Among recently diagnosed cases (since 1995), there was some suggestion of a greater proportion of aggressive tumors for those with any family history (69% and 55%) vs. none (50%) (P = 0.20). We found little evidence of large differences between familial and sporadic NHL with regard to age, gender, site or histologic subtype.
Patterns of conduction in smooth muscle.

In sheets of circular intestinal muscle, electrical waves conduct in all directions, much faster and with less decrement in the long than in the transverse axis of the fibers. Need for interfiber summation is shown by failure to initiate conducted spikes with stimulating electrodes less than 100 µ diameter. Conduction is in bands with occasional entry from one band into another. Minimal latency occurs in a 1–2-mm band in line with stimulating electrodes. Diagonal conduction was not observed, but double spikes represent direct conduction followed by re-entry into a band from a parallel conducting path. Records with double microelectrodes, 1–700 µ apart, showed no measurable latency difference when both were in the same fiber but normal velocity at separations greater than 50 µ.
Experimental evidence for negative selection in the evolution of a Yersinia pestis pseudogene

Yersinia pestis, the agent of bubonic plague, evolved from the enteric pathogen Yersinia pseudotuberculosis within the past 20,000 years. Because ancestor and descendant both exist, it is possible to infer steps in molecular evolution by direct experimental approaches. The Y. pestis life cycle includes establishment of a biofilm within its vector, the flea. Although Y. pseudotuberculosis makes biofilms in other environments, it fails to do so in the insect. We show that rcsA, a negative regulator of biofilms that is functional in Y. pseudotuberculosis, is a pseudogene in Y. pestis. Replacement of the pseudogene with the functional Y. pseudotuberculosis rcsA allele strongly represses biofilm formation and essentially abolishes flea biofilms. The conversion of rcsA to a pseudogene during Y. pestis evolution, therefore, was a case of negative selection rather than neutral genetic drift.