Miracle-dz/UniFAR-FTUs huggingface dataset:
Multistage carcinogenesis: population-based model for colon cancer.

BACKGROUND Recent laboratory work and previous models suggest that multiple mutations are associated with the development of colon cancer. PURPOSE AND METHODS To estimate the number of mutations required for colon carcinogenesis, we used likelihood analysis to obtain the best fit between mathematical models postulating different numbers of rate-limiting events and data on incidence rates of colon cancer in two human populations--the general population of Birmingham, England, from 1968 to 1972 and patients with familial adenomatous polyposis (FAP) diagnosed at Saint Mark's Hospital, London, England, between 1925 and 1965. The Armitage-Doll model and two- and three-mutation models that explicitly incorporated cell proliferation kinetics were used. RESULTS When cell kinetics were considered, models postulating either two or three rate-limiting events described the incidence rates of colon cancer equally well in both human populations. A comparison of the incidence rate of colon cancer in the general population with that in patients with polyposis suggests that a mutation at the FAP gene locus is not one of the rate-limiting events in colon carcinogenesis. CONCLUSIONS Compared with the two-mutation model, the three-mutation model was more consistent with the number of mutations reported to date in colon cancer and with mutation rates measured in the laboratory. IMPLICATIONS A mutation at the FAP locus may not be a rate-limiting step but may act indirectly by stimulating the proliferation of stem cells. Thus, the development of colon cancer in patients with FAP does not appear to fit the retinoblastoma paradigm.
Collagen Synthesis in Virus‐transformed Cells a

One of the most striking effects of viral transformation on the biosynthetic program of cultured cells is the reduced synthesis of collagen, which often occurs together with decreased synthesis of other extracellular matrix proteins. The resulting loss of the normal extracellular matrix is associated with the dramatic changes in cell shape and behavior observed in transformed cells. Several laboratories have begun to examine the molecular basis for the reduction of collagen synthesis. In this paper we summarize those results, and describe recent experiments from our laboratories which examine in detail the effects of transformation on collagen synthesis in skin fibroblasts and vertebral chondrocytes, two terminally differentiated populations of mesenchymal cells from chick embryos. These cells synthesize very different types of extracellular matrix and display different responses to viral transformation in terms of collagen gene expression. The results of these experiments have led us to suggest that synthesis of type I1 collagen, which occurs almost exclusively in terminally differentiated chondrocytes, is controlled primarily at the level of transcription. In contrast, synthesis of type I collagen, which occurs in many cells (but not in chondrocytes), is controlled at post-transcriptional as well as transcriptional levels. Furthermore, expression of both the types I and I1 collagen genes is modulated by alterations in cell shape which are mediated by cell attachment. These observations have important implications for the control of collagen gene expression during normal development, as well as for the effects of viral transformation on collagen gene expression. In addition, they may increase our understanding of the complex interplay between cell shape and behavior and synthesis of collagen and other components of the extracellular matrix.
Rapid Communication SOLICITATION FOR LETTERS OF INTENT Clinical trials Preclinical experiments E7389, Halichondrin B analog (NSC 707389)

CTEP is soliciting for phase 1 combination and phase 2 single-agent clinical trials of E7389, a halichondrin B analogue tubulin polymerization inhibitor. E7389 is being developed by CTEP in collaboration with Eisai Research Institute (Eisai). E7389 is also available for nonclinical studies via the NCI through a cooperative agreement with Eisai. CTEP is specifically interested in experiments that will generate data useful for prioritization of clinical combination studies, mechanism of action studies, and studies to evaluate radiation sensitization.
ASSESSMENT OF LOWER LIMB ASYMMETRY: DIFFERENCES DURING ISOMETRIC AND STRETCH-SHORTENING CYCLE TASKS

Assessment of limb function asymmetry is of interest to practitioners due to its role in return to play guidelines and reported links to injury. Dynamometry is one of the most commonly used methods of assessing muscle function, but the mode of contraction used is different to the stretch-shortening cycles experienced during real-life activities. The aim of this study was to compare measures of limb function asymmetry during isometric and stretch-shortening cycle tasks and investigate agreement between the methods. Different between-limb effect sizes were observed between limbs dependent on test used, with different ranges of asymmetry observed. Agreement between methods was very poor. These results show the importance of assessing asymmetry in a condition that is as similar as possible to the task of interest.
Oocyte donation using immature oocytes from a normal ovulatory woman

Oocyte donation is a well-established treatment for some infertile patients. The main problem with an oocyte donation program is the limited source of donors. The discomfort and risks associated with ovarian stimulation and oocyte retrieval limit the availability of donors. Recovery of immature oocytes followed by in vitro maturation (IVM) is a potential alternative of infertility treatment. This technique saves tedious ovarian stimulation and may greatly improve a woman’s willingness to be an oocyte donor. Pregnancies resulting from immature oocyte donation of Cesarean section or PCOS women have been reported (1), although the pregnancy rates were very low. Recent reports by Chian et al. proposed that by giving human chorionic gonadotropin (HCG) before immature oocyte recovery from polycystic ovary syndrome (PCOS) women, the pregnancy rate could be significantly improved (2). We reported here the first case of pregnancy resulting from immature oocyte donation, after priming with HCG, from a normal ovulatory woman with polycystic appearing ovaries. Unfortunately, this pregnancy ended up as an ectopic pregnancy.
In Vitro Activity of a Purified Natural Anion Channelrhodopsin*

Natural anion channelrhodopsins (ACRs) recently discovered in cryptophyte algae are the most active rhodopsin channels known. They are of interest both because of their unique natural function of light-gated chloride conductance and because of their unprecedented efficiency of membrane hyperpolarization for optogenetic neuron silencing. Light-induced currents of ACRs have been studied in HEK cells and neurons, but light-gated channel conductance of ACRs in vitro has not been demonstrated. Here we report light-induced chloride channel activity of a purified ACR protein reconstituted in large unilamellar vesicles (LUVs). EPR measurements establish that the channels are inserted uniformly “inside-out” with their cytoplasmic surface facing the medium of the LUV suspension. We show by time-resolved flash spectroscopy that the photochemical reaction cycle of a functional purified ACR from Guillardia theta (GtACR1) in LUVs exhibits similar spectral shifts, indicating similar photocycle intermediates as GtACR1 in detergent micelles. Furthermore, the photocycle rate is dependent on electric potential generated by chloride gradients in the LUVs in the same manner as in voltage-clamped animal cells. We confirm with this system that, in contrast to cation-conducting channelrhodopsins, opening of the channel occurs prior to deprotonation of the Schiff base. However, the photointermediate transitions in the LUVs exhibit faster kinetics. The ACR-incorporated LUVs provide a purified defined system amenable to EPR, optical and vibrational spectroscopy, and fluorescence resonance energy transfer measurements of structural changes of ACRs with the molecules in a demonstrably functional state.
Pharmacogenomics in the Curricula of Colleges and Schools of Pharmacy in the United States

Objectives. To assess the breadth, depth, and perceived importance of pharmacogenomics instruction and level of faculty development in this area in schools and colleges of pharmacy in the United States. Methods. A questionnaire used and published previously was further developed and sent to individuals at all US schools and colleges of pharmacy. Multiple approaches were used to enhance response. Results. Seventy-five (83.3%) questionnaires were returned. Sixty-nine colleges (89.3%) included pharmacogenomics in their PharmD curriculum compared to 16 (39.0%) as reported in a 2005 study. Topic coverage was <10 hours for 28 (40.6%), 10–30 hours for 29 (42.0%), and 31–60 hours for 10 (14.5%) colleges and schools of pharmacy. Fewer than half (46.7%) were planning to increase course work over the next 3 years and 54.7% had no plans for faculty development related to pharmacogenomics. Conclusions. Most US colleges of pharmacy include pharmacogenomics content in their curriculum, however, the depth may be limited. The majority did not have plans for faculty development in the area of pharmacogenomic content expertise.
Spike frequency adaptation studied in hypoglossal motoneurons of the rat.

1. We studied spike frequency adaptation of motoneuron discharge in the rat hypoglossal nucleus using a brain stem slice preparation. The characteristics of adaptation in response to long (60 s) injected current steps were qualitatively similar to those observed previously in cat hindlimb motoneurons. The discharge rate typically exhibited a rapid initial decline, characterized by a linear frequency-time relation, followed by a gradual exponential decline that continued for the duration of current injection. However, a more systematic, quantitative analysis of the data revealed that there were often three distinct phases of the adaptation rather than two. 2. The three phases of adaptation (initial, early, and late) were present in at least one 60-s trial of repetitive firing in all but a small number of motoneurons. Initial adaptation was limited to the first few spikes except in a few trials (7%) in which there was no initial adaptation. The time course of the subsequent decline in rate could be adequately described by a single-exponential function in about half of the trials (48%). In the remaining trials this subsequent decline in frequency was better described as the sum of two exponential functions: an early phase, lasting < 2 s, and a late phase, which lasted for the duration of the discharge period. 3. The magnitude of initial adaptation was correlated with the initial firing frequency (i.e., the reciprocal of the 1st interspike interval). The magnitudes of the early and late phases of adaptation were correlated with the firing frequency reached at the end of initial adaptation. Neither the magnitudes nor the time courses of the three phases were correlated with other membrane properties such as input resistance, rheobase, or repetitive firing threshold. 4. The slope of the frequency-current (f-I) curve was steeper in the initial phase (first 2-5 spikes) than in either the early (< 2 s) or late (> 2 s) phases of adaptation as previously reported by other investigators. In the absence of early adaptation, a steady state for the f-I slope was reached by 0.7-1 s, the time typically reported in studies of repetitive discharge. However, when early adaptation was present (50% of the trials), a steady-state value for the f-I slope was not reached until the cell had discharged for > 1 s. 5. To characterize the time course of firing rate recovery from the adaptive processes, the current was turned off for periods of < or = 10 s during the course of a 60-s trial. (ABSTRACT TRUNCATED AT 400 WORDS)
Osteoporosis in Children With Severe Congenital Neutropenia: Bone Mineral Density and Treatment With Bisphosphonates

A high incidence of decreased bone mineral density (BMD) has been described in patients with severe congenital neutropenia (SCN). The objectives of the study are to describe changes in BMD in children with SCN treated with granulocyte colony-stimulating factor and evaluate the response to treatment with bisphosphonates in those who had osteoporosis. A prospective open-label study was performed evaluating BMD and metabolism in 9 Chilean patients with SCN, administrating bisphosphonates in those with osteoporosis. Follow-up ranged between 7 months and 3.5 years. Six out of 9 patients had reduced BMD on initial assessment: 3 had osteoporosis (z score<−2) and 3 had osteopenia (z score <−1). Four children presented vertebral fractures. Two presented osteopenia on follow-up without clinical symptoms. Five patients were treated with bisphosphonates, increasing their BMD z score (mean increase 1.2, range 0.27 to 2.62). z Score of hydroxyproline/creatinine ratios, which was elevated in 4 patients with osteoporosis, decreased during treatment (mean decrease 2.18, range 1.56 to 2.53). Four patients remodeled and reexpanded fractured vertebrae during treatment. No side effects of bisphosphonates were seen on follow-up. Osteoporosis is an important comorbidity in SCN patients probably due to increased bone resorption. Bisphosphonates seem to be an effective treatment for osteoporosis in these patients.
Chinese Medicine in Action: On the Postcoloniality of Medical Practice in China

Since the early twentieth century, there has been strong opposition to Chinese medicine within Chinese society. Critics have attacked Chinese medicine as unscientific and a hindrance to the development of the nation. I argue that doctors of Chinese medicine have responded to this charge by developing a “postcolonial” form of medicine that is based on the celebrated methodology of “pattern recognition and treatment determination bianzheng lunzhi . ” I show that bianzheng lunzhi plays two contradictory roles in everyday clinical practice, distinguishing the uniqueness of Chinese medicine from biomedicine while providing a technology for integrating these two medical practices. Through the close examination of a typical medical case, I show how these dual processes of purification and hybridization have become the central dynamic in the postcolonial transformation of Chinese medicine.
Under-registration of occupational diseases: the Greek case.

employees or 47%of the total labour force, have been eligible to seekstatutory compensation for 52 occupational diseases.Here, we report the numbers and diagnoses of patientswho were accepted as having a recognized occupationaldisease under the scheme in 2001.Of the 82 claims, 50 were accepted, an overall rate of2.6 per 100000 registered employees. Their mean agewas 55 years (SD ¼ 6 years), 88% were male and 96%were in manual employment. Diagnoses (mainly respir-atory or dermatological) and current occupations aredisplayed in Table 1. A single case of mesothelioma wasreported.These ﬁgures strongly suggest that occupationaldiseases are under-recognized in Greece. Even with theinclusion of 17 further cases registered after appeal, therate of 3.4/100000 is, by far, the lowest in the EuropeanUnion [2]. Agricultural workers, merchant seamen andmost professionals are registered under alternativeschemes without a prescribed list and so occupationaldisease in these groups would not be represented here.Furthermore, despite the country’s major asbestosindustry, just one case of pleural mesothelioma hasbeen registered; indeed, pleural mesothelioma is not evenincludedintheoriginal list of 52prescribed diseases.Twocases of mesothelioma among Greek merchant seamenwerepublishedin1991[3],butseamenareregistered inascheme without a prescribed list. In Greece, the reportingof occupational diseases is mandatory, thus, under-registration probably reﬂects, alongside the very lowcompensation awards, a lack of occupational attribution.There are few specialist occupational physicians and forseveral large employment groups, for example the healthservice, there is no structured occupational healthprovision. Furthermore, IKA is the only social insurancescheme in the country with a prescribed list. We believethat the registered occupational morbidity reﬂectsthe state of occupational health in Greece.
Memory, Attention, and Choice

We present a theory in which the choice set cues a consumer to recall a norm, and surprise relative to the norm shapes his attention and choice. We model memory based on Kahana (2012), where past experiences that are more recent or more similar to the cue are recalled and crowd out others. We model surprise relative to the norm using our salience model of attention and choice. The model predicts unstable and inconsistent behavior in new contexts, because these are evaluated relative to past norms. Under some conditions, repeated experience causes norms to adapt, inducing stable – sometimes rational – behavior across different contexts. We test some of the model’s predictions using an expanded data set on rental decisions of movers between US cities first analyzed by Simonsohn and Loewenstein (2006).
The Perceived Role of General Self-Regulation and Prosocial Support on the Decision Not to Act Among Men Sexually Attracted to Children

Recent research highlights potential differences between groups of men sexually attracted to children regarding child molestation behavior, attitudes toward sex with children, and the decision not to act on their attractions. The present study furthered this line of research by investigating the roles of general self-regulation and prosocial support on the decision not to act among 69 men sexually attracted to children. Mixed-methods analysis of survey results provided mixed evidence regarding their relevance to refraining from engaging in child molestation behavior. Quantitative results suggested that self-control, but not prosocial support, showed a major influence on participants’ decision not to act. Qualitative results offered a more nuanced understanding of the roles of both of these factors in participants’ decisions. Overall, findings support an approach for investigating men sexually attracted to children that focuses on differences between men who do and do not act on their attractions, as well as on the active decision to refrain from engaging in child molestation behavior. Implications for research and clinical practice are highlighted.
Immunoprophylaxis and immunotherapy for a murine fibrosarcoma with C. Granulosum and C. Parvum

Prophylactic and therapeutic effectiveness of killed C. granulosum and C. parvum bacteria was investigated against a methylcholanthrene‐induced fibrosarcoma in syngeneic C3Hf/Bu mice. Subcutaneous or intravenous treatment of mice with 0.25 mg of these bacteria greatly reduced the number of tumor nodules (metastases, colonies) in the lung generated by 105 or 106 fibrosarcoma cells inoculated intravenously 7 days later. The treatment also prolonged the survival of tumor‐cell recipients, and to some mice afforded complete protection against tumor growth. Number of lung metastases and survival of the recipients were more affected by intravenous than by subcutaneous treatment with the bacteria. Given intravenously to mice 3 days after intravenous inoculation of 2×105 fibrosarcoma cells, these non‐specific immunostimulants significantly reduced the number of pulmonary colonies and prolonged survival of mice. In contrast, subcutaneous application of the bacteria was only slightly effective. Both C. granulosum and C. parvum administered intravenously to mice 3 days following subcutaneous injection of 4×105 fibrosarcoma cells did not affect the development of subcutaneous tumors. However, when the tumors had grown to 25‐17 mm in diameter 67% and 80% of them underwent complete and lasting regressions in mice treated with C. granulosum and C. parvum, respectively. C. granulosum and C. parvum were approximately equally effective against both intravenously and subcutaneously injected tumor cells.
Actinobacillus sp. bacteremia in foals: clinical signs and prognosis.

Medical records of 101 blood culture-confirmed bacteremic foals were reviewed to determine whether foals with Actinobacillus sp. bacteremia are affected at an earlier age, have more severe signs of disease, and have a worse prognosis than do foals with bacteremia of other causes. Thirty percent (30/101) of bacteremic foals had Actinobacillus sp. cultured, and these were 2 times more likely to die (crude odds ratio [OR(CR)] 0.8, 4; P = . 14), with a survival rate of 43% (13/30) compared to the overall survival rate of 55% (56/101). When compared to other bacteremic foals, foals with actinobacillosis were 7 times more likely to have been sick from birth (adjusted odds ratio [OR(ADJ)] 2, 26; P = . 003) and 6 times more likely to have diarrhea (OR(ADJ) 1, 22; P = . 009). By bivariate analysis. foals with Actinobacillus sp. bacteremia were 5 times more likely to have a sepsis score >11 (OR(CR) 1, 18; P = . 007), 6 times more likely to be obtunded (OR(CR) 2, 20; P = . 005), and 3 times more likely to have pneumonia (OR(CR) 1, 7; P = . 03). Furthermore, Actinobacillus sp. bacteremic foals were 27 times more likely to have a segmented neutrophil count <3.3 X 10(9) cells/L (OR(ADJ) 4, 166: P < . 0001) and were 4.5 times more likely to have a band neutrophil count >0.46 x 10(9) cells/L (OR(ADJ) 1, 17; P = . 02) when compared to foals that had bacteremia caused by either gram-negative enteric or gram-positive organisms. Sepsis score was < or = 11 in 49% (29/59) of bacteremia foals aged <13 days for which a discernible sepsis score was calculable. Results of this study should improve the diagnostic sensitivity of clinical examinations of neonatal foals, thereby facilitating treatment decisions.
Clinical Appraisal of TURP in Gezira Hospital for Renal Diseases and Surgery

Transurethral resection of the prostate(TURP) is the gold standard for the surgical treatment of benign prostatic hyperplasia(BPH)-related lower urinary tract symptoms (LUTS). Objective : The main goal is to evaluate patients selection the complications and the outcome following TURP in (Gezira hospital for renal diseases and surgery) GHRDS. Methodology : This study was a prospective, hospital based, small scale study conducted in the period between January 2012 to June 2013 in Gezira Hospital for Renal Diseases and Surgery. Ninety four patients underwent TURP for (benign prostatic hyperplasia) BPH were included in this study. The management was done according to the European association of urological surgeons (EAU) guideline for the indication of surgery, procedure and postoperative treatment.The data was collected in a form of data sheet (patient's records, direct interviews and a pre-designed questionnaire). Data coded and fed in computer to handle statistical and mathematical procedure, using SPSS 17(statistical package for social sciences). Result : One hundred and thirty two patients were enrolled, twenty one patients were excluded due tunneling TURP for Ca prostate and 17 had incomplete follow up or record. Mean age of (69.02) years, mean hospital stay (1.5) days, mean follow-up of (7.19) month and mean operation time was (39.9) minute. Fortunately no mortality stated with significant improvement in international prostate symptoms score ( IPSS) on the long term (87.2%) and minimal complication like perforation occur in 2 patients (2.1%), while 1 patient (1.1%) develop bleeding. Conclusion : The outcome of TURP in GHRDS is good with minimum intraoperative and postoperative complications.