Miracle-dz/UniFAR-FTUs huggingface dataset:
Randomized Double-Blind Trial of Sulindac and Etodolac to Eradicate Aberrant Crypt Foci and to Prevent Sporadic Colorectal Polyps

Purpose: On the basis of the results of our preliminary trial suggesting that aberrant crypt foci (ACF) could be eradicated by short-term administration of sulindac, in the present study, we explored the feasibility of using ACF as surrogate markers for chemoprevention of colorectal cancer. Experimental design: Randomly assigned to sulindac (300 mg daily), etodolac (400 mg daily), and placebo groups were 189 subjects without polyps or who had undergone polypectomy. Drugs were administered for 2 months. ACF in the rectal region were counted by magnifying endoscopy. Occurrence of polyps was evaluated at 12 months. A planned interim analysis was conducted. Results: ACF number at 2 months was significantly suppressed in the sulindac group (P = 0.0075), but not in the etodolac group (P = 0.73). In the sulindac group, the numbers of adenomas plus hyperplastic polyps (total polyps) and adenomas at 12 months were significantly (P = 0.02) and marginally (P = 0.064) lower, respectively, in comparison with the placebo group; no such difference was observed in the etodolac group. In analysis of only polypectomized subjects, the numbers of total polyps and adenomas in the sulindac group were even more markedly lower, with P values of 0.014 and 0.034, respectively. A similar tendency was confirmed by analyses of the incidence of polyps at 12 months. Suppression rates of total polyps and adenomas in ACF responders to sulindac were significantly greater than in nonresponders. In all groups, compliance was more than 90% and no intolerable adverse effects were observed. Conclusions: ACF may be useful as surrogate lesions for chemoprevention of colorectal cancer. Clin Cancer Res; 17(11); 3803–11. ©2011 AACR.
Learning the Information Divergence

Information divergence that measures the difference between two nonnegative matrices or tensors has found its use in a variety of machine learning problems. Examples are Nonnegative Matrix/Tensor Factorization, Stochastic Neighbor Embedding, topic models, and Bayesian network optimization. The success of such a learning task depends heavily on a suitable divergence. A large variety of divergences have been suggested and analyzed, but very few results are available for an objective choice of the optimal divergence for a given task. Here we present a framework that facilitates automatic selection of the best divergence among a given family, based on standard maximum likelihood estimation. We first propose an approximated Tweedie distribution for the β-divergence family. Selecting the best β then becomes a machine learning problem solved by maximum likelihood. Next, we reformulate α-divergence in terms of β-divergence, which enables automatic selection of α by maximum likelihood with reuse of the learning principle for β-divergence. Furthermore, we show the connections between γ- and β-divergences as well as Renyi- and α-divergences, such that our automatic selection framework is extended to non-separable divergences. Experiments on both synthetic and real-world data demonstrate that our method can quite accurately select information divergence across different learning problems and various divergence families.
The efficacy of combination of ondansetron and aprepitant on preventing the radiotherapy-induced nausea and vomiting

Background: Depending on the site of irradiation, about 40-80% of patients undergoing radiotherapy (RT) will experience nausea and/or vomiting. The current study aimed to investigate the efficacy of ondansetronas as a single agent and with a combination to aprepitant on preventing RT-induced nausea and vomiting (RINV). Materials and Methods: In a clinical randomized controlled trial (from September 2010 to September 2011), conducted in Radiation Oncology Department of Seyed-al-Shohada Hospital, Isfahan University of Medical Sciences, 40 abdominopelvic malignancies cancer patients were allocated into two aliquots using block randomization of size. Patients in the first group (group I) received ondansetron alone while those patients in the remaining group (group II) received ondansetron and aprepitant. Then, developing of RINV and its severity and benefit of adding aprepitant to ondansetron, in comparison with ondansetron as a single drug therapy were evaluated. Results: The average age of the patients in group I was 61.15 ± 12.27 years while in group II it was 50.1 ± 13.27 years. No statistically significant gender differences were found between the two groups. In patients treated with ondansetron single drug therapy (group I), frequency and grade of RINV were significantly more than the group treated simultaneously by aprepitant and ondansetron (group II) (odds ratio [OR] = 21.2; P < 0.01). Compared with RT alone, the patients whom underwent RT along with chemotherapy showed lower probability of experiencing RINV (OR = 0.13; P < 0.05). Conclusion: The present study indicated a significant superiority of combination of ondansetron and aprepitant in management of RINV, in patients undergoing RT, compared to ondansetron as a single agent therapy. More accurate follow-up studies are needed for the evaluation of the efficacy of ondansetron with combination to aprepitant on preventing the RINV.
Confounding Factors in HGT Detection: Statistical Error, Coalescent Effects, and Multiple Solutions

Prokaryotic organisms share genetic material across species boundaries by means of a process known as horizontal gene transfer (HGT). This process has great significance for understanding prokaryotic genome diversification and unraveling their complexities. Phylogeny-based detection of HGT is one of the most commonly used methods for this task, and is based on the fundamental fact that HGT may cause gene trees to disagree with one another, as well as with the species phylogeny. Using these methods, we can compare gene and species trees, and infer a set of HGT events to reconcile the differences among these trees. In this paper, we address three factors that confound the detection of the true HGT events, including the donors and recipients of horizontally transferred genes. First, we study experimentally the effects of error in the estimated gene trees (statistical error) on the accuracy of inferred HGT events. Our results indicate that statistical error leads to overestimation of the number of HGT events, and that HGT detection methods should be designed with unresolved gene trees in mind. Second, we demonstrate, both theoretically and empirically, that based on topological comparison alone, the number of HGT scenarios that reconcile a pair of species/gene trees may be exponential. This number may be reduced when branch lengths in both trees are estimated correctly. This set of results implies that in the absence of additional biological information, and/or a biological model of how HGT occurs, multiple HGT scenarios must be sought, and efficient strategies for how to enumerate such solutions must be developed. Third, we address the issue of lineage sorting, how it confounds HGT detection, and how to incorporate it with HGT into a single stochastic framework that distinguishes between the two events by extending population genetics theories. This result is very important, particularly when analyzing closely related organisms, where coalescent effects may not be ignored when reconciling gene trees. In addition to these three confounding factors, we consider the problem of enumerating all valid coalescent scenarios that constitute plausible species/gene tree reconciliations, and develop a polynomial-time dynamic programming algorithm for solving it. This result bears great significance on reducing the search space for heuristics that seek reconciliation scenarios. Finally, we show, empirically, that the locality of incongruence between a pair of trees has an impact on the numbers of HGT and coalescent reconciliation scenarios.
MHD equilibrium variational principles with symmetry

The chain rule for functionals is used to reduce the noncanonical Poisson bracket for magnetohydrodynamics (MHD) to one for axisymmetric and translationally symmetric MHD and hydrodynamics. The procedure for obtaining Casimir invariants from noncanonical Poisson brackets is reviewed and then used to obtain the Casimir invariants for the considered symmetrical theories. It is shown why extrema of the energy plus Casimir invariants correspond to equilibria, thereby giving an explanation for the ad hoc variational principles that have existed in plasma physics. Variational principles for general equilibria are obtained in this way.
Trabeculotomy for the treatment of glaucoma after Descemet stripping endothelial keratoplasty

Descemet stripping endothelial keratoplasty (DSEK) is a surgical procedure designed for the selective replacement of diseased endothelium that causes bullous keratopathy.1 This procedure provides excellent anatomic results and more rapid visual rehabilitation than penetrating keratoplasty (PKP). Glaucoma after PKP is not rare, but glaucoma after DSEK is not reported. We report on four glaucoma patients after DSEK treated by trabeculotomy with successful results. All the consecutive patients had DSEK performed from July 2006 to January 2007. Written informed consents were obtained from all patients prior to surgery. Two patients were male, and two patients were female. The mean (SD) age was 72.0 (8.4) years (range 60–79). Two patients were pseudophakic bullous keratopathy, and two patients were laser-iridotomy-induced bullous …
High Kellgren-Lawrence Grade and Bone Marrow Lesions Predict Worsening Rates of Radiographic Joint Space Narrowing; The SEKOIA Study

Objective. Determinants of radiographic progression in osteoarthritis (OA) are poorly understood. We investigated which features on baseline magnetic resonance imaging (MRI) acted as predictors of change in joint space width (JSW). Methods. A total of 559 men and women over the age of 50 years with clinical knee OA [Kellgren-Lawrence (KL) grade 2–3] were recruited to the placebo arm of the SEKOIA study (98 centers; 18 countries). Minimal tibiofemoral joint space and KL grade on plain radiograph of the knee were assessed at baseline and at yearly followup up to 3 years. In a subset, serial knee MRI examinations were performed. Individuals with a bone marrow lesion (BML) ≥ grade 2 at the tibiofemoral joint at baseline were classified as BML-positive. Relationships between change in JSW and risk factors were assessed using linear regression. Results. The mean age of study participants was 62.8 (SD 7.5) years and 73% were female; 38.6% had BML. Mean baseline JSW was 3.65 mm. This reduced by 0.18 (0.30) mm/year in men and 0.13 (0.23) mm/year in women. Those with BML had a significantly higher rate of annualized change in JSW; this relationship remained robust after adjustment for age, sex, and baseline KL grade [β = −0.10 (95% CI −0.18, −0.02) mm/yr]. Age, sex, baseline KL grade, and other MRI findings did not influence the rate of change in JSW. Conclusion. The rate of change in JSW was similar in men and women. BML on knee MRI predicted the rate of radiographic change in JSW. This relationship was independent of age, sex, and baseline KL grade.
Once more on the BPS bound for the susy kink

We consider a new momentum cut-off scheme for sums over zero-point energies, containing an arbitrary function f(k) which interpolates smoothly between the zero-point energies of the modes around the kink and those in flat space. A term proportional to df(k)/dk modifies the result for the one-loop quantum mass M^(1) as obtained from naive momentum cut-off regularization, which now agrees with previous results, both for the nonsusy and susy case. We also introduce a new regularization scheme for the evaluation of the one-loop correction to the central charge Z^(1), with a cut-off K for the Dirac delta function in the canonical commutation relations and a cut-off \Lambda for the loop momentum. The result for Z^(1) depends only on whether K>\Lambda or K<\Lambda or K=\Lambda. The last case yields the correct result and saturates the BPS bound, M^(1)=Z^(1),in agreement with the fact that multiplet shortening does occur in this N=(1,1) system. We show how to apply mode number regularization by considering first a kink-antikink system, and also obtain the correct result with this method. Finally we discuss the relation of these new schemes to previous approaches based on the Born expansion of phase shifts and higher-derivative regularization.
The Biology of Cancer Stem Cells and Its Clinical Implication in Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is a highly malignant tumor with limited treatment options in its advanced state. The molecular mechanisms underlying HCC remain unclear because of the complexity of its multi-step development process. Cancer stem cells (CSCs) are defined as a small population of cells within a tumor that possess the capability for self-renewal and the generation of heterogeneous lineages of cancer cells. To date, there have been two theories concerning the mechanism of carcinogenesis, i.e., the stochastic (clonal evolution) model and the hierarchical (cancer stem cell-driven) model. The concept of the CSC has been established over the past decade, and the roles of CSCs in the carcinogenic processes of various cancers, including HCC, have been emphasized. Previous experimental and clinical evidence indicated the existence of liver CSCs; however, the potential mechanistic links between liver CSCs and the development of HCC in humans are not fully understood. Although definitive cell surface markers for liver CSCs have not yet been found, several putative markers have been identified, which allow the prospective isolation of CSCs from HCC. The identification and characterization of CSCs in HCC is essential for a better understanding of tumor initiation or progression in relation to signaling pathways. These markers could be used along with clinical parameters for the prediction of chemoresistance, radioresistance, metastasis and survival and may represent potential targets for the development of new molecular therapies against HCC. This review describes the current evidence for the existence and function of liver CSCs and discuss the clinical implications of CSCs in patients demonstrating resistance to conventional anti-cancer therapies, as well as clinical outcomes. Such data may provide a future perspective for targeted therapy in HCC.
Frequency of Iatrogenic Errors through Root Canal Treatment Procedure in 1335 Charts of Dental Patients

Background: Endodontic procedures such as root canal treatment would be at the risk of failure like other medical interventions due to any unsuitable conditions. This has a causative effect in making the procedure more complicated to resulting in weak prognosis finally. Technical errors such as ledge, perforation, obstruction, broken instrument, etc. make infection control too hard or impossible. The aims of this study are common errors frequency and types of root canal treatments focusing on defined groups of dental students in Qazvin, Iran. Materials and Methods: All the errors were divided into three major kinds of: (1) During providing access cavity, (2) cleaning and preparation and (3) canal obturation. Results: A total number of 1335 charts of the cases were studied in the field of root canal treatment. The whole number of charts, which reported errors was 880 (66%) while 455 (34%) error-free ones. The most frequent error in upper incisors was void with the rate of 50.9%, followed by overfilling (apical perforation) in 18.2%. The same errors were also most common for lower incisors in addition to imperfect cleaning. Conclusions: The current study identified the least mistakes through the process of providing access cavity and instrumentation phase comparing obturation phase, which had the most frequent errors including void, overfilling and imperfect cleaning.
Relative role of changes in CO₂ and climate to equilibrium responses of net primary production and carbon storage of the terrestrial biosphere

In a partial factorial model experiment, we used the Terrestrial Ecosystem Model (TEM, version 4.0) to assess the relative roles of changes in CO2, temperature, precipitation and cloudiness in equilibrium responses of primary production and carbon storage. In the experiment, we used two levels of atmospheric CO2 concentration (315 and 522 ppmv CO2), contemporary climate and changes in temperature, precipitation and cloudiness as estimated by a 3-dimensional atmospheric general circulation model (Geophysical Fluid Dynamic Laboratory-GFDL) and a 2-dimensional climate model (Land-Ocean climate model at Massachusetts Institute of Technology) for doubled CO2. The results show that elevated CO2 and projected increases in temperature account for most of the overall equilibrium responses of NPP and carbon storage to changes in climate and CO2, while the projected changes in precipitation and cloudiness contribute least. This is partly attributable to the magnitudes of changes in CO2 and climate variables as projected by the climate models. The results also show that the interactions among changes in CO2 and climate variables play a significant role in the equilibrium responses of NPP and carbon storage to changes in CO2 and climate. Of all the interaction terms, the interaction between a change in CO2 and a change in temperature is the most significant.
A MATHEMATICAL MODEL OF HUMAN THYMIDINE KINASE 2 ACTIVITY

The mitochondrial enzyme thymidine kinase 2 (TK2) phosphorylates deoxythymidine (dT) and deoxycytidine (dC) to form dTMP and dCMP, which in cells rapidly become the negative-feedback end-products dTTP and dCTP. TK2 kinetic activity exhibits Hill coefficients of ∼0.5 (apparent negative cooperativity) for dT and ∼1 for dC. We present a mathematical model of TK2 activity that is applicable if TK2 exists as two monomer forms in equilibrium.
Spatio-Temporal Patterns of Key Exploited Marine Species in the Northwestern Mediterranean Sea

This study analyzes the temporal variability/stability of the spatial distributions of key exploited species in the Gulf of Lions (Northwestern Mediterranean Sea). To do so, we analyzed data from the MEDITS bottom-trawl scientific surveys from 1994 to 2010 at 66 fixed stations and selected 12 key exploited species. We proposed a geostatistical approach to handle zero-inflated and non-stationary distributions and to test for the temporal stability of the spatial structures. Empirical Orthogonal Functions and other descriptors were then applied to investigate the temporal persistence and the characteristics of the spatial patterns. The spatial structure of the distribution (i.e. the pattern of spatial autocorrelation) of the 12 key species studied remained highly stable over the time period sampled. The spatial distributions of all species obtained through kriging also appeared to be stable over time, while each species displayed a specific spatial distribution. Furthermore, adults were generally more densely concentrated than juveniles and occupied areas included in the distribution of juveniles. Despite the strong persistence of spatial distributions, we also observed that the area occupied by each species was correlated to its abundance: the more abundant the species, the larger the occupation area. Such a result tends to support MacCall's basin theory, according to which density-dependence responses would drive the expansion of those 12 key species in the Gulf of Lions. Further analyses showed that these species never saturated their habitats, suggesting that they are below their carrying capacity; an assumption in agreement with the overexploitation of several of these species. Finally, the stability of their spatial distributions over time and their potential ability to diffuse outside their main habitats give support to Marine Protected Areas as a potential pertinent management tool.
Interaction of Ca2+ agonist and depolarization on Ca2+ channel current in guinea pig detrusor cells [published erratum appears in J Gen Physiiol 1996 Jun;107(6):755]

The interaction of large depolarization and dihydropyridine Ca2+ agonists, both of which are known to enhance L-type Ca2+ channel current, was examined using a conventional whole-cell clamp technique. In guinea pig detrusor cells, only L-type Ca2+ channels occur. A second open state (long open state: O2) of the Ca2+ channels develops during large depolarization (at +80 mV, without Ca2+ agonists). This was judged from lack of inactivation of the Ca2+ channel current during the large depolarizing steps (5 s) and slowly deactivating inward tail currents (= 10-15 ms) upon repolarization of the cell membrane to the holding potential (-60 mV). Application of Bay K 8644 (in 2.4 mM Ca(2+)- containing solutions) increased the amplitude of the Ca2+ currents evoked by simple depolarizations, and made it possible to observe inward tail currents (= 2.5-5 ms at -60 mV). The open state induced by large depolarization (O2*) in the Bay K 8644 also seemed hardly to inactivate. After preconditioning with large depolarizing steps, the decay time course of the inward tail currents upon repolarization to the holding potential (-60 mV) was significantly slowed, and could be fitted reasonably with two exponentials. The fast and slow time constants were 10 and 45 ms, respectively, after 2 s preconditioning depolarizations. Qualitatively the same results were obtained using Ba2+ as a charge carrier. Although the amplitudes of the inward currents observed in the test step and the subsequent repolarization to the holding potential were decreased in the same manner by additional application of nifedipine (in the presence of Bay K 8644), the very slow deactivation time course of the tail current was little changed. The additive enhancement by large depolarization and Ca2+ agonists of the inward tail current implies that two mechanisms separately induce long opening of the Ca2+ channels: i.e., that there are four open states.
Pediatric Anesthesia Morbidity and Mortality in the Perioperative Period

One of the most frequent questions asked of a pediatric anesthesiologist is “What are the risks of anesthesia for my child? ” Unfortunately, few studies have examined the consequences of general anesthesia in children. We used data from a large pediatric anesthesia follow-up program at Winnipeg Children's Hospital (1982–1987) to determine rates of perioperative adverse events among children of different ages. A check-off form was completed by a pediatric anesthesiologist for each case (n = 29,220) and a designated follow-up reviewer examined all anesthesia forms and hospital charts to ascertain adverse effects for children less than 1 mo, 1–12 mo, 1–5 yr, 6–10 yr, and 11–16 yr of age in the intraoperative, recovery room, and postoperative periods. The majority of the children were healthy, and 70% had no preoperative medical conditions. Infants less than 1 mo old were more likely to be undergoing major cardiac or vascular procedures, whereas the older children had mainly orthopedic or otolaryngologic procedures. Infants less than 1 mo old had the highest rate of adverse events both intraoperatively and in the recovery room. The main problem in this age group was related to the respiratory and cardiovascular systems. In children over 5 yr of age, postoperative nausea and vomiting was very frequent, with about one-third of the children experiencing this problem. When all events were considered (both major and minor), there was a risk of an adverse event in 35% of the pediatric cases. This contrasts with 17% for adults. This morbidity survey helps to focus on areas of intervention and for further study.