Miracle-dz/UniFAR-FTUs huggingface dataset:
Clinical Trials of a Low Molecular Weight Matrix Metalloproteinase Inhibitor in Cancer

Matrix metalloproteinases (MMPs) first received broad recognition as the proteinases thought to be responsible for joint degeneration in rheumatoid arthritis,lJ and it was with this end point in mind that many pharmaceutical companies established research programs in the early 1980s with the goal of obtaining clinically useful low molecular weight MMP inhibitors. It is therefore perhaps a little surprising that one of the first indications to be pursued in the clinic would be the treatment of malignant ascites. This paper reviews some of the developments that have led to the clinical trial of a low molecular weight MMP inhibitor in cancer.
Childhood adversity and adult psychiatric disorder in the US National Comorbidity Survey

Background. Survey data are presented on the associations between retrospectively reported childhood adversities and subsequent onset and persistence of DSM-III-R disorders. Methods. Data come from the US National Comorbidity Survey, a large survey of the US household population. Results. Twenty-six adversities were considered, including loss events (e.g. parental divorce), parental psychopathologies (e.g. maternal depression), interpersonal traumas (e.g. rape) and other adversities (e.g. natural disaster). These adversities were consistently associated with onset, but not persistence, of DSM-III-R mood disorders, anxiety disorders, addictive disorders and acting out disorders. Most bivariate associations with onset attenuated in models that controlled for clustering of adversities and for lifetime co-morbidities among psychiatric disorders. Multivariate effects of adversities in logistic models were additive, which means that they have multiplicative effects on probability of disorder onset. Adversities showed little specificity. An analysis of time decay showed that the effects of childhood adversities on disorder onset persist beyond childhood. Conclusions. The existence of strong clustering among childhood adversities and lifetime co-morbidity among adult disorders means that caution is needed in interpreting the results of previous single-adversity single-disorder studies as documenting unique effects of specific childhood adversities on specific adult disorders. Future studies need to assess a broader range of adversities and disorders and to explore the existence and effects of commonly occurring adversity clusters. Replication is needed to verify that the effects of childhood adversities are mostly on first onset rather than on the creation of vulnerabilities that lead to increased risk of persistence.
Osteoporosis Health Beliefs Among Younger and Older Men and Women

The purpose of this study was to compare osteoporosis health beliefs among different age and gender groups. This study used a cross-sectional design, involved 300 participants that represent both genders and three age groups (18 to 25, 30 to 50, and 50-plus), and assessed osteoporosis health beliefs using the Osteoporosis Health Belief Scale (OHBS). Factor analysis revealed three subscales of OHBS: perceived susceptibility, seriousness of the condition, and health motivation to take preventative actions with acceptable levels of reliability. Significant age and gender differences were observed in the susceptibility scores of the OHBS. The perceived seriousness of the osteoporosis scores was similar across all age and gender groups, as was health motivation. These results highlight the need for osteoporosis awareness programs targeting different aspects of belief perceptions, specifically for younger women and men.
Phase III trial in metastatic gastroesophageal adenocarcinoma with fluorouracil, leucovorin plus either oxaliplatin or cisplatin: a study of the Arbeitsgemeinschaft Internistische Onkologie.

PURPOSE This study was designed to compare fluorouracil, leucovorin, and oxaliplatin with fluorouracil, leucovorin, and cisplatin in patients with advanced gastric cancer. PATIENTS AND METHODS Patients with previously untreated advanced adenocarcinoma of the stomach or esophagogastric junction were randomly assigned to receive either fluorouracil 2,600 mg/m(2) via 24-hour infusion, leucovorin 200 mg/m(2), and oxaliplatin 85 mg/m(2) (FLO) every 2 weeks or fluorouracil 2,000 mg/m(2) via 24-hour infusion, leucovorin 200 mg/m(2) weekly, and cisplatin 50 mg/m(2) every 2 weeks (FLP). The primary end point was progression-free survival (PFS). RESULTS Two hundred twenty patients (median age, 64 years; metastatic, 94%) were randomly assigned. FLO was associated with significantly less (any grade) anemia (54% v 72%), nausea (53% v 70%), vomiting (31% v 52%), alopecia (22% v 39%), fatigue (19% v 34%), renal toxicity (11% v 34%), thromboembolic events (0.9% v 7.8%), and serious adverse events related to the treatment (9% v 19%). FLP was associated with significantly less peripheral neuropathy (22% v 63%). There was a trend toward improved median PFS with FLO versus FLP (5.8 v 3.9 months, respectively; P = .077) and no significant difference in median overall survival (10.7 v 8.8 months, respectively). However, in patients older than 65 years (n = 94), treatment with FLO resulted in significantly superior response rates (41.3% v 16.7%; P = .012), time to treatment failure (5.4 v 2.3 months; P < .001), and PFS (6.0 v 3.1 month; P = .029) and an improved OS (13.9 v 7.2 months) as compared with FLP, respectively. CONCLUSION FLO reduced toxicity as compared with FLP. In older adult patients, FLO also seemed to be associated with improved efficacy.
The clinical implications of early diastolic notch in third trimester Doppler waveform analysis of the uterine artery.

To evaluate the clinical utility of third trimester Doppler waveform analysis of the uterine artery in predicting complicated pregnancies and fetal well‐being, we compared adverse pregnancy outcomes in 2321 women with the presence of an elevated systolic‐diastolic ratio (greater than 2.6) with the persistence of an early diastolic notch and with the combination of an elevated systolic‐diastolic ratio and an early diastolic notch. The positive predictive values are 47.5%, 82.9%, and 92.6%, respectively. From these data we can conclude that determination of the presence or absence of an early diastolic notch is more valuable in predicting the perinatal outcome than is the presence of an elevated systolic‐diastolic ratio alone. We also suggest that an assessment of the uterine artery systolic‐diastolic ratio combined with the evaluation for persistent early diastolic notch would be a clinically useful test for fetal well‐being.
Fission Yeast Mad3p Is Required for Mad2p To Inhibit the Anaphase-Promoting Complex and Localizes to Kinetochores in a Bub1p-, Bub3p-, and Mph1p-Dependent Manner

ABSTRACT The spindle checkpoint delays the metaphase-to-anaphase transition in response to spindle and kinetochore defects. Genetic screens in budding yeast identified the Mad and Bub proteins as key components of this conserved regulatory pathway. Here we present the fission yeast homologue of Mad3p. Cells devoid of mad3+ are unable to arrest their cell cycle in the presence of microtubule defects. Mad3p coimmunoprecipitates Bub3p, Mad2p, and the spindle checkpoint effector Slp1/Cdc20p. We demonstrate that Mad3p function is required for the overexpression of Mad2p to result in a metaphase arrest. Mad1p, Bub1p, and Bub3p are not required for this arrest. Thus, Mad3p appears to have a crucial role in transducing the inhibitory “wait anaphase” signal to the anaphase-promoting complex (APC). Mad3-green fluorescent protein (GFP) is recruited to unattached kinetochores early in mitosis and accumulates there upon prolonged checkpoint activation. For the first time, we have systematically studied the dependency of Mad3/BubR1 protein recruitment to kinetochores. We find Mad3-GFP kinetochore localization to be dependent upon Bub1p, Bub3p, and the Mph1p kinase, but not upon Mad1p or Mad2p. We discuss the implications of these findings in the context of our current understanding of spindle checkpoint function.
Percutaneous core biopsy of the breast: effect of operator experience and number of samples on diagnostic accuracy.

OBJECTIVE The purpose of our study was to assess the degree of operator experience and the number of core biopsy samples required to achieve an accurate histologic diagnosis for each of five common mammographically defined lesions, using percutaneous core breast biopsy performed on a dedicated prone biopsy table. SUBJECTS AND METHODS A prospective multisite study was performed that involved nine institutions (academic and private) with experienced breast radiologists and the use of dedicated prone biopsy table units with digital assistance and standardized protocol. Asymptomatic women evaluated during a 2-year study period were assigned a mammographic diagnosis reported in a manner prescribed by the American College of Radiology Breast Imaging Reporting and Data System lexicon. Mammographic lesions evaluated included masses, masses with calcifications, clustered calcifications, focal asymmetries, and architectural distortions. Where histologic diagnosis was indicated, core biopsy was performed with five individual samples obtained and sequentially analyzed. Two hundred thirty patients had immediate excisional biopsy, the results of which provided the basis for a statistical analysis to compare the accuracy of each sequential core biopsy sample with surgical results. Statistical analysis was also done to ascertain the accuracy of core biopsy diagnosis as a function of operator experience. RESULTS Trends toward increasing accuracy were observed by increasing the number of core biopsies for each of five types of mammographically defined lesions, especially for clustered calcifications. Statistically significant increased accuracy was observed when the number of biopsies was increased beyond one (p = .003). Trends toward increased accuracy with more experience were observed for all lesions, especially for calcifications. Of the 230 lesions studied with immediate surgical validation, more than 80% of all lesions except clustered calcifications (75%) were diagnosed on the basis of two core biopsies; accuracy after five biopsies was 98% for masses, 91% for calcifications, 100% for masses with calcification, 100% for focal asymmetries, and 86% for architectural distortions. CONCLUSIONS Accuracy of diagnosis based on the results of percutaneous core breast biopsy improved with an increase in the number of core biopsy samples obtained for any given lesion seen on mammograms and with increased experience in performing the procedure. Five samples yielded an overall diagnostic accuracy of 97%. Familiarity with expected accuracy from this procedure for different mammographic lesions and following increased experience may assist physicians in planning patient management.
Alternate Flight Control Mechanisms : Transfer Effects in Simulated Flight

Competing aircraft and simulator manufacturers are currently incorporating dissimilar flight control systems into commercial aircraft and training equipment. In response to such industry developments, a recently emerging field of aviation training transfer research is examining the distinctiveness of conventional and alternate flight control systems and their underlying transfer relationships. This paper recounts a series of experiments where human skill acquisition in simulated flight was examined to identify differences between transfer effects facilitated by yoke and stick flight control systems. Flight naïve adult participants twice completed a sequence of visual approach to landing trials in a low fidelity fixed based synthetic flight trainer using either a yoke or a stick. Participants either utilised the same control mechanism throughout the study or participants converted between the alternate systems across experimental phases. Assessment phases were conducted one week apart with vertical deviations from a constant 3-degree glideslope being analysed. The collective research provides evidence of positive transfer of training in low fidelity flight training equipment and that a performance difference exists between the stick and the yoke. Results consistently revealed a lower rate of performance error resulted from use of the yoke compared to the stick.
Powers of Horror: An Essay on Abjection

I. Approaching Abjection2. Something to Be Scared Of3. From Filth to Defilement4. Semiotics of Biblical Abomination5. Qui Tollis Peccata Mundi6. C line: Neither Actor nor Martyr7. Suffering and Horror8. Those Females Who Can Wreck the Infinite9. "Ours to Jew or Die"10. In the Beginning and Without End.11. Powers of Horror
Hyperuricemia after liver transplantation in children

Abstract: Uric acid may be involved in the development and progression of kidney diseases. Hyperuricemia is a common feature in adult liver transplant recipients but there is limited information in children. In order to estimate the incidence, predictors of hyperuricemia in pediatric liver transplant recipients, and to assess whether hyperuricemia may impact long‐term renal function determined by measured GFR, we reviewed data of 70 children who received a first liver transplant between 1991 and 2005 (median follow‐up 7.1 yr). Renal function tests performed annually included uric acid concentration, inulin and uric acid clearances. The cumulative incidence of hyperuricemia was 32% at 10‐yr post‐transplantation, mainly because of decreased urate excretion. The only factor significantly associated with an increased risk of hyperuricemia was older age. After adjustment for donor and recipient age, gender, primary liver disease, immunosuppression, and post‐operative acute renal failure, hyperuricemia as time dependent variable tended to predict (p = 0.05) subsequent CRI. The control of serum urate concentration in eight of the 21 hyperuricemic patients either by nutritional management or by allopurinol was not followed by a significant GFR improvement. Hyperuricemia after liver transplantation in children is a frequent problem which needs further investigation.
Regional Greenland accumulation variability from Operation IceBridge airborne accumulation radar

Abstract. The mass balance of the Greenland Ice Sheet (GrIS) in a warming climate is of critical interest to scientists and the general public in the context of future sea-level rise. An improved understanding of temporal and spatial variability of snow accumulation will reduce uncertainties in GrIS mass balance models and improve projections of Greenland's contribution to sea-level rise, currently estimated at 0.089 ± 0.03 m by 2100. Here we analyze 25 NASA Operation IceBridge accumulation radar flights totaling > 17 700 km from 2013 to 2014 to determine snow accumulation in the GrIS dry snow and percolation zones over the past 100–300 years. IceBridge accumulation rates are calculated and used to validate accumulation rates from three regional climate models. Averaged over all 25 flights, the RMS difference between the models and IceBridge accumulation is between 0.023 ± 0.019 and 0.043 ± 0.029 m w.e. a−1, although each model shows significantly larger differences from IceBridge accumulation on a regional basis. In the southeast region, for example, the Modele Atmospherique Regional (MARv3.5.2) overestimates by an average of 20.89 ± 6.75 % across the drainage basin. Our results indicate that these regional differences between model and IceBridge accumulation are large enough to significantly alter GrIS surface mass balance estimates. Empirical orthogonal function analysis suggests that the first two principal components account for 33 and 19 % of the variance, and correlate with the Atlantic Multidecadal Oscillation (AMO) and wintertime North Atlantic Oscillation (NAO), respectively. Regions that disagree strongest with climate models are those in which we have the fewest IceBridge data points, requiring additional in situ measurements to verify model uncertainties.
1 Human Papillomavirus : Biology and Pathogenesis

The human papillomavirus (HPV) is one of the most common causes of sexually transmitted disease in both men and women around the world, especially in developing countries, where the prevalence of asymptomatic infection varies from 2 to 44%, depending on the population and studied region (Sanjosé et al., 2007). Most HPV infection is transient and some studies show that the majority of sexually active individuals are exposed to and acquire infection from this virus at some phase in their lives (Baseman and Koutsky, 2005; Trottier and Franco, 2006). HPV infection is more prevalent in young adults, at the beginning of their sexual activity, with a subsequent decline in the prevalence rate with increasing age, likely as a result of development of an immune response against the virus and reduction of sexual activity (Castle et al., 2005; Fernandes et al., 2009; Chan et al., 2010).
Circulating Angiotensin II Activates Neurones in Circumventricular Organs of the Lamina Terminalis That Project to the Bed Nucleus of the Stria Terminalis

The aim of this study was to determine, in conscious rats, whether elevated concentrations of circulating angiotensin II activate neurones in both the subfornical organ and organum vasculosum of the lamina terminalis (OVLT) that project to the bed nucleus of the stria terminalis (BNST). The strategy employed was to colocalize retrogradely transported cholera toxin B subunit (CTB) from the BNST, with elevated levels of Fos protein in response to angiotensin II. Circulating angiotensin II concentrations were increased by either intravenous infusion of angiotensin II or subcutaneous injection of isoproterenol. Neurones exhibiting Fos in response to angiotensin II were present in the subfornical organ, predominantly in its central core but with some also seen in its peripheral aspect, the dorsal and lateral margins of the OVLT, the supraoptic nucleus and the parvo‐ and magnocellular divisions of the paraventricular nucleus. Fos‐labelling was not apparent in control rats infused with isotonic saline intravenously or injected with either CTB or CTB conjugated to gold particles (CTB‐gold) only. Of the neurones in the subfornical organ that were shown by retrograde labelling to project to BNST, approximately 50% expressed Fos in response to isoproterenol. This stimulus also increased Fos in 33% of neurones in the OVLT that project to BNST. Double‐labelled neurones were concentrated in the central core of the subfornical organ and lateral margins of the OVLT in response to increased circulating angiotensin II resulting from isoproterenol treatment. These data support a role for circulating angiotensin II acting either directly or indirectly on neurones in subfornical organ and OVLT that project to the BNST and provide further evidence of functional regionalization within the subfornical organ and the OVLT. The function of these pathways is yet to be determined; however, a role in body fluid homeostasis is possible.
The ratio of MMP-2 to TIMP-2 in hilar cholangiocarcinoma: a semi-quantitative study.

BACKGROUND Hilar cholangiocarcinoma is associated with low resectability and poor survival. The aim of this study was to evaluate the roles of matrix metalloproteinases-2 (MMP-2) and its tissue inhibitor of metalloproteinase-2(TIMP-2) in tumor invasion or as a prognostic factor in patients with human hilar cholangiocarcinoma. METHODS The expressions of MMP-2 and TIMP-2 were investigated in patients. Paraffinized tissue sections obtained from 50 patients with human hilar cholangiocarcinoma were analysed. The expressions of MMP-2 and TIMP-2 were examined immunohistochemically. Image analysis with image-pro plus analysis software was used to semiquantitatively determine the ratio of MMP-2 to TIMP-2. RESULTS The expression levels of MMP-2 and TIMP-2 were strongly associated with tumor hepatic invasion in patients with hilar cholangiocarcinoma. Significant differences in the ratio of MMP-2 to TIMP-2 between some pathologic factors were observed in patients with hilar cholangiocarcinoma. CONCLUSIONS MMP-2 plays an essential role in tumor invasion and metastasis, while TIMP-2 is shown to strongly inhibit cancer invasion and metastasis. The ratio of MMP-2 to TIMP-2 may be a prognostic indicator for patients with hilar cholangiocarcinoma.
Speculations About the Indo-European Cardinals 5-10

SUMMARYOn the basis of some recent research in Indo-European phonology and morphology, it is suggested in this paper that the IE cardinals 5 to 10 were subject to affixation by non-singular markers. These markers, probably originating as quantitative enclitic adverbs, were added to these numerals in order to hypercharacterize their inherent non-singular meaning. Specifically, it is proposed that '5', '7', '8', '9', and '10' were all hypercharacterized by the suffix *-n, while '6' was hypercharacterized by the suffix *-s. In addition, dialectal data imply that within Indo-European '7' and '10' showed the non-singular element *-t, generally in contamination with *-n. Such an assessment represents a major departure from the traditional view that in Indo-European these numerals, with the exception of '8', were uninflected forms.RESUMECet article suggere, a la base de certaines recherches sur la pho-nologie et la morphologie indo-europennes, que les nombres cardinaux 5 a 10 en indo-europeen avaient ete soumis a une affixation avec des marqueurs 'non-singulier'. Ces marqueurs, venant probablement d'ad-verbes clitiques quantitatifs, ont ete ajoutes a ces chiffres afin de surcaracteriser leur sens inherent de 'non-singulier'. En particulier, il est propose que '5', '7', '8', '9' et '10' etaient tous surcaracte-rises par le suffixe *-n, tandis que '6' etait surcaracterise par le suffixe *-s, De plus, des donnees dialectales suggerent qu'a l'interi-eur de '7' et '10' indo-europeen il y avait l'element non-singulier *-t, generalement contamine avec *-n. Une telle analyse represente un ecart important par rapport avec 1'acceptation traditionnelle selon laquelle ces chiffres indo-europeens, a l'exception de '8! , etaient des formes sans flexion (i.e., invariables). ZUSAMMENFASSUNGIn diesem Aufsatz wird der Vorschlag gemacht, auf Grundlage jiing-ster Untersuchungen auf dem Gebiete der idg. Laut- und Formenlehre, das die idg. Kardinalzahlen 5 bis 10 'nicht-Singular' Merkzeichen in der Form eines Affixes trugen. Diese Merkzeichen, die wahrscheinlich in en-klitischen, quantitativen Adverbien ihren Ursprung haben, wurden diesen Ziffern beigefugt, urn ihre ihnen innewohnende nicht-singulare Bedeutung uberzubetonen. Insbesondere wird der Vorschlag gemacht, das die Ziffern '5', '7', '8', '9' und '10' alle durch das Suffix *-n ubercharakterisiert waren, wahrend dies im Falle von der Ziffer '6' durch Anfiigung von *-s geschah. Daruberhinaus legen es dialektale Daten nahe, das innerhalb des Indogermanischen die Ziffern '7' und '10' das nicht-singullire Element *-t aufwiesen, und zwar zumeist in Kontamination mit *~s. Eine sol-che Interpretation der Materialien bedeutet eine wichtige Abriickung von der traditionellen Auffassung, derzufolge diese Zahlworter des Indogermanischen, mit Ausnahme der '8', unflektierte Formen gewesen seien.