Miracle-dz/UniFAR-FTUs huggingface dataset:
Efficacy and toxicity of adjuvant chemotherapy in elderly patients with colorectal cancer: the ACCORE study

Background Elderly patients with primary colorectal cancer (CRC) are less frequently treated with adjuvant chemotherapy than younger patients due to concerns regarding toxicity and efficiency. We investigated how age, performance status (PS) and comorbidity influence treatment outcomes. Patients and methods A retrospective single-centre study of 529 patients with stages II–III CRC treated with adjuvant chemotherapy (5-fluorouracil/capecitabine+/÷oxaliplatin) from 2001 to 2011 at Herlev Hospital, Denmark. Baseline characteristics, chemotherapy and outcome were analysed with respect to age after adjusting for PS and comorbidity. Results Elderly patients (>70 years) had significantly more comorbidity (p<0.001) and poorer PS (p=0.001) than younger patients. Elderly were more frequently treated with single-agent therapy (p=0.001) and at lower initial dose (p<0.001). There was no age-dependent difference in 3-year disease-free survival (DFS; HR 1.09, 95% CI 0.80 to 1.47, p=0.59), in grade 3–5 toxicity (29% vs 28%, p=0.86) or in 10-year CRC mortality (28%, HR 1.07, p=0.71). In elderly patients, a reduction in chemotherapy dose intensity compared with full dose had no impact on DFS or CRC mortality. Elderly patients receiving <50% of planned cycles had shorter DFS (HR=1.78, p=0.020) and higher CRC mortality (HR=2.17, p=0.027) than elderly receiving all cycles. Poor PS in younger and elderly patients was related to shorter DFS (HR=1.95, p=0.002; HR=1.6, p=0.035, respectively) and overall survival (OS; HR=2.28, p<0.001; HR=2.03, p=0.002). Comorbidity in younger patients was significantly related to shorter DFS (HR 2.72, p<0.001), OS (HR 3.16, p<0.001) and higher CRC mortality (HR 2.70, p=0.001). Conclusions Choice of regimen, primary dose reduction and given dose intensity in patients treated with adjuvant chemotherapy for CRC were highly dependent on age. However, age had no impact on DFS and CRC mortality. Comorbidity in younger patients and PS in all patients were associated with shorter DFS and higher CRC mortality.
A kinetically defined Na+/H+ antiporter within a mathematical model of the rat proximal tubule

The luminal membrane antiporter of the proximal tubule has been represented using the kinetic formulation of E. Heinz (1978. Mechanics and Engergetics of Biological Transport. Springer-Verlag, Berlin) with the assumption of equilibrium binding and 1:1 stoichiometry. Competitive binding and transport of NH+4 is included within this model. Ion affinities and permeation velocities were selected in a least-squares fit to the kinetic parameters determined experimentally in renal membrane vesicles (Aronson, P.S., M.A. Suhm, and J. Nee. 1983. Journal of Biological Chemistry. 258:6767-6771). The modifier role of internal H+ to enhance transport beyond the expected kinetics (Aronson, P.S., J. Nee, and M. A. Suhm. 1982. Nature. 299:161-163) is represented as a velocity effect of H+ binding to a single site. This kinetic formulation of the Na+/H+ antiporter was incorporated within a model of the rat proximal tubule (Weinstein, A. M. 1994. American Journal of Physiology. 267:F237-F248) as a replacement for the representation by linear nonequilibrium thermodynamics (NET). The membrane density of the antiporter was selected to yield agreement with the rate of tubular Na+ reabsorption. Simulation of 0.5 cm of tubule predicts that the activity of the Na+/H+ antiporter is the most important force for active secretion of ammonia. Model calculations of metabolic acid-base disturbances are performed and comparison is made among antiporter representations (kinetic model, kinetic model without internal modifier, and NET formulation). It is found that the ability to sharply turn off Na+/H+ exchange in cellular alkalosis substantially eliminates the cell volume increase associated with high HCO3- conditions. In the tubule model, diminished Na+/H+ exchange in alkalosis blunts the axial decrease in luminal HCO3- and thus diminishes paracellular reabsorption of Cl-. In this way, the kinetics of the Na+/H+ antiporter could act to enhance distal delivery of Na+, Cl-, and HCO3- in acute metabolic alkalosis.
Effects of Dantrolene on Rat Diaphragm Muscle during Postnatal Maturation

Background Dantrolene is the only known effective treatment for malignant hyperthermia. However, its effects on diaphragm muscle during postnatal maturation remain unknown. Methods The effects of dantrolene (10−8 to 10−4 m) were investigated in vitro on diaphragm muscle strips in adult rats and in postnatal rats aged 3, 10, and 17 days, and compared with those of ryanodine (10−8 to 10−6 m). The authors studied contraction and relaxation under isotonic and isometric conditions (29°C, Krebs-Henseleit solution, tetanic stimulation at 50 Hz). Data are mean ± SD. Results During postnatal maturation, the authors observed a progressive increase in active force developed per cross- sectional area (from 34 ± 25 to 69 ± 32 mN/mm2;P < 0.05) and maximum shortening velocity (from 2.9 ± 0.5 to 4.9 ± 1.4 Lmax/s;P < 0.05). Dantrolene induced a negative inotropic effect in diaphragm muscles in isotonic and isometric conditions in all groups, but this effect was significantly less marked in the 3-day-old rats compared with older rats. Dantrolene did not induce significant lusitropic effects during postnatal maturation. Developmental changes in the pharmacologic response to dantrolene were more rapid than those of ryanodine. Conclusion Dantrolene induced less pronounced negative inotropic effects on the diaphragm in neonatal rats as compared with adult rats. Our study suggests that developmental changes in the pharmacologic response to dantrolene are more rapid than those of ryanodine.
What clinicians should know about the QT interval.

CONTEXT Of the several factors implicated in causing QT interval prolongation and torsades de pointes, errors in the use of medications that may prolong this interval deserve special attention. OBJECTIVE To systematically summarize the available clinical data on the QT interval and to offer improved recommendations for the use of QT-prolonging medications. DATA SOURCES We searched MEDLINE from 1966 through 2002 for all English-language articles related to the QT interval. Additional data sources included bibliographies of articles identified on MEDLINE, a survey of experts, and data presented at a meeting of experts on long QT syndrome. STUDY SELECTION We selected for review registries and case series examining clinical outcomes of patients with prolonged QT interval and the effect of different methods of measurement of the QT interval on patient outcomes. Ten studies were identified, of which 6 were included in the analysis. DATA EXTRACTION Data quality was determined by publication in the peer-reviewed literature. DATA SYNTHESIS Optimal measurement of the QT interval is problematic because of lack of standardization and lack of data regarding the best way to adjust for heart rate. Reliable information on the proper use of QT-prolonging medications is scarce. Although a QT interval of at least 500 milliseconds generally has been shown to correlate with a higher risk of torsades de pointes, there is no established threshold below which prolongation of the QT interval is considered free of proarrhythmic risk. The risk of torsades de pointes should be assessed in patients who are about to begin taking a QT-prolonging medication. Although inadequate clinical studies preclude prediction of absolute risk for individual patients, particularly high-risk situations can be defined based on clinical variables. We propose recommendations on proper monitoring of the QT interval in patients receiving QT-prolonging medications. CONCLUSION Although the use of QT-prolonging medications can predispose to torsades de pointes, there is a relative paucity of information that can help clinicians and patients make optimal informed decisions about how best to minimize the risk of this serious complication.
The role of nicotinamide in acne treatment

Safe and effective treatment options for acne vulgaris are needed to address side effects and increasing rates of antibiotic resistance from current treatments. Nicotinamide is a vitamin with potent anti‐inflammatory properties that could offer a potential treatment option. We aim to summarize the relevant literature on the role of nicotinamide in acne vulgaris and discuss the next steps necessary to move this approach into clinical practice. We searched PubMed for clinical studies using nicotinamide for treatment of acne vulgaris. We summarized the 10 studies that met our search criteria. Six of eight studies using topical nicotinamide led to a significant reduction in acne compared with the patient's baseline or performed similarly to another standard‐of‐care acne treatment. Both studies using an oral supplement containing nicotinamide resulted in a significant reduction in acne compared with baseline. No major adverse side effects were noted. Our review suggests that topical and oral nicotinamide has an unclear effect on acne vulgaris due to the limited nature of the available literature. Additional studies are needed comparing nicotinamide to other first‐line acne treatments and evaluating the efficacy and side effect profile of nicotinamide over an extended period of time.
Orthography Affects Second Language Speech: Double Letters and Geminate Production in English

Second languages (L2s) are often learned through spoken and written input, and L2 orthographic forms (spellings) can lead to non-native-like pronunciation. The present study investigated whether orthography can lead experienced learners of EnglishL2 to make a phonological contrast in their speech production that does not exist in English. Double consonants represent geminate (long) consonants in Italian but not in English. In Experiment 1, native English speakers and EnglishL2 speakers (Italians) were asked to read aloud English words spelled with a single or double target consonant letter, and consonant duration was compared. The EnglishL2 speakers produced the same consonant as shorter when it was spelled with a single letter, and longer when spelled with a double letter. Spelling did not affect consonant duration in native English speakers. In Experiment 2, effects of orthographic input were investigated by comparing 2 groups of EnglishL2 speakers (Italians) performing a delayed word repetition task with or without orthographic input; the same orthographic effects were found in both groups. These results provide arguably the first evidence that L2 orthographic forms can lead experienced L2 speakers to make a contrast in their L2 production that does not exist in the language. The effect arises because L2 speakers are affected by the interaction between the L2 orthographic form (number of letters), and their native orthography–phonology mappings, whereby double consonant letters represent geminate consonants. These results have important implications for future studies investigating the effects of orthography on native phonology and for L2 phonological development models.
Fast matrix completion without the condition number

We give the first algorithm for Matrix Completion whose running time and sample complexity is polynomial in the rank of the unknown target matrix, linear in the dimension of the matrix, and logarithmic in the condition number of the matrix. To the best of our knowledge, all previous algorithms either incurred a quadratic dependence on the condition number of the unknown matrix or a quadratic dependence on the dimension of the matrix in the running time. Our algorithm is based on a novel extension of Alternating Minimization which we show has theoretical guarantees under standard assumptions even in the presence of noise.
Efficiency improvement of AlGaInN LEDs advanced by ray-tracing analysis

A modified ray-tracing model is applied to analyze the dependence of external quantum efficiency and far-field radiation pattern of AlGaInN light-emitting diodes (LEDs) on various device parameters. Considerable increase (about 1.5 times) in the efficiency is predicted for LEDs with highly reflective p-contact as compared to those with the semitransparent p-contact. It is shown that the LED's efficiency degrades with the increasing of the optical loss in AlGaInN epitaxial layers as well as with increasing of the LED chip area. The ways of improving the external efficiency of large-area (and thus, powerful) LEDs are discussed including utilization of a textured (light-scattering) backside of sapphire substrate or a diffusive interface between epitaxial layers and p-contact.
Fatal Shift of Signal Transduction Is an Integral Part of Neuronal Differentiation: JNKs Realize TNFα-Mediated Apoptosis in Neuronlike, but Not Naive, PC12 Cells

Tumor necrosis factor-alpha (TNFalpha, 10-100 ng/ml) provokes a dramatic cell death in differentiated PC12 cells (dPC12), but it does not affect the viability and the proliferation of naive PC12 cells (nPC12). We have analyzed the molecular alterations of the TNFalpha-signal cascade underlying this developmental switch toward propagation of apoptosis. The transcriptional inhibitor actinomycin D rendered nPC12 responsive for TNFalpha-induced death, but was hardly effective in dPC12, suggesting that TNFalpha evokes its harmful action in dPC12 predominantly by posttranslational modification of existing molecules. This suggestion was supported by the finding that differentiation of PC12 per se went along with the increased expression of the proapoptotic TNFalpha-receptor I (p55) and its adapter protein Traf-2, whereas expression and phosphorylation of the antiapoptotic Akt (PKB) declined. We could demonstrate that the c-Jun N-terminal kinases (JNKs) mediate this enhanced capacity of apoptotic signaling in dPC12. TNFalpha induced in dPC12, but not nPC12, a biphasic activation of JNKs with a rapid transient JNK1 activation and a second persistent activation of JNK1 and JNK2 paralleled by phosphorylation of c-Jun; in contrast, TNFalpha did not activate p38 kinase. Block of JNKs by CEP-11004, a MLK antagonist and subsequently indirect inhibitor of JNK activation, or L-JNK11, a direct peptidergic inhibitor of JNK activity, almost completely rescued dPC12. Summarizing, the NGF-triggered formation of neurites during differentiation of PC12 includes the reinforced propensity for apoptosis, with JNK2 as the effector in JNK3-negative PC12. These findings offer novel insights into the increased risk of neuronal death, which is linked to the potential to regenerate.
Response of near-isogenic sorghum lines, differing at the P locus for plant colour, to grain mould and head smut fungi

Leaves and stalks of many sorghum genotypes accumulate dark red or purple pigments upon wounding while some plants, called ‘tan,’ do not. Grains with unpigmented ‘white’ pericarps grown on tan plants are more desirable for food. The hypothesis tested was that pigments in plants protected grain against the panicle diseases grain mould and head smut. Near-isogenic tan or purple plant colour genotypes with white grain were planted at Lincoln and Ithaca, NE and Corpus Christi, TX. The field grown grain was plated onto semi-selective media to detect the presence of grain colonisation by mould genera Alternaria, Fusarium and Curvularia . M oreFusarium and Curvularia spp. were recovered from grain grown at Corpus Christi than the Nebraska locations; however, there was no indication that the grain from purple plants was more resistant to the three fungal genera. Most fungi were identified morphologically as Alternaria alternata. Molecular identification of Fusarium species, using translation elongation factor 1-α gene sequences, showed that Fusarium thapsinum and Fusarium proliferatum infected grain at all three locations. Head smut disease of panicles, caused by the fungus Sporisorium reilianum, was assessed at Corpus Christi; surprisingly, purple plants had significantly greater disease incidence than tan plants. We propose that the tan plant colour lines with white grain are promising for development of foodgrade sorghums not more susceptible than pigmented lines to grain mould and head smut.
From the Economics of Privacy to the Economics of Big Data

Imagine a world in which consumers’ preferences can be so precisely estimated by observing their online behavior, that firms are able to anticipate consumers’ needs, offering the right product at exactly the right time. Imagine that same world, but now consider that extensive knowledge of consumers’ preferences also allows precise inferences about their reservation prices (the maximum price each consumer will pay for a good), so that firms can charge different prices for the same product to each of their buyers, and absorb the entire surplus arising from an economic transaction. Imagine a world in which the collection and analysis of individual health data allow researchers to discover the causes of rare deceases and the cures for common ones. Now, consider the same world, but imagine that employers are able to predict job candidates’ future health conditions from few data points extracted from the latter’s social network
Characteristics of patients with pancreatic cancer expressing a novel cancer cachectic factor

Recently a novel tumour‐derived cachectic factor was identified in the murine MAC16 colonic adenocarcinoma model of cachexia. This factor, provisionally named proteolysis‐inducing factor (PIF), was subsequently identified in the urine of weight‐losing patients with cancer but not in the urine of weight‐stable patients with cancer or weight‐losing controls with benign disease. This study determined the nutritional characteristics of patients with pancreatic cancer who excrete PIF in the urine and investigated the relationship between PIF and the acute‐phase protein response.
Mycosis Fungoides: Epidemiology in Isfahan, Iran

Background: Mycosis Fungoides (MF) is the most common and indolent form of Cutaneuse T-cell Lymphomas (CTCL), that usually occurs in old adults. Objectives: To determine epidemiologic features and patients characteristics of MF in Isfahan (Iran). Methods: We performed a retrospective study in MF clinic of alzahra hospital that is the main center for treatment of MF patients in Isfahan (Iran) and evaluated clinicopathologic features. Results: In 3 years 25 patients were referred to Alzahra MF clinic. 18 patients diagnosed as MF. Seven (38.9%) patients were male and 11 (61.1%) were female with male to female ratio of 1:1.57. The mean age of patients was 41.06 years. 88.9% of our patients were in stages ΙA and ΙB. Conclusion: Most of our patients presented in early stages that were similar to other studies, while male: female ratio is different from other studies.
Effects of intramuscular testosterone undecanoate on body composition and bone mineral density in female-to-male transsexuals.

INTRODUCTION The most common treatment regimen in female-to-male transsexuals is administration of short-acting testosterone esters intramuscularly every 2 weeks. AIM The aim of this study was to evaluate the effect of long-acting intramuscular testosterone undecanoate on body composition and bone mineral density during cross-sex hormone therapy in female-to-male transsexuals. METHODS Forty-five female-to-male transsexuals (FtMs) were treated with injections of testosterone undecanoate 1,000 mg intramuscularly every 12 weeks over 24 months. MAIN OUTCOME MEASURES Body composition, bone mineral density, hormone parameters, and lipids were compared after 12 months and after 24 months with baseline values. Sonographic findings in the ovaries and endometrium, clinical and adverse effects during the study period were recorded. RESULTS There was a significant increase in lean mass in the FtMs during the study period in comparison with baseline values, whereas no change in BMI, fat mass, and bone mineral density was observed. There was a significant decline in gonadotropins, estradiol, dehydroepiandrosterone sulphate, sex hormone-binding globulin, and high-density lipoprotein, while testosterone and triglyceride levels increased significantly after 12 and 24 months. Ovaries remained unchanged and no noticeable endometrial pathology was observed. No mortality or morbidity was observed during the study period. We observed a cessation of menstrual bleeding, an increase in clitoral growth, libido, body and beard hair growth, deepened voices and decline in breast size. There was a significant increase in hemoglobin, hematocrit, glutamic-pyruvic transaminase, gamma-glutamyl transferase, and an increase in systolic blood pressure during the study period. CONCLUSIONS There was an increase in lean mass during the study period in FtMs treated with testosterone undecanoate. Transsexual patients should be monitored for adverse effects on lipid profiles, blood pressure, and erythrocytosis during intramuscular testosterone undecanoate therapy.
Near-Optimal and Practical Jamming-Resistant Energy-Efficient Cognitive Radio Communications

This paper studies the problem of jamming-resistant spectrum aggregation and access (SAA) for energy-efficiency (EE) cognitive radio communications. We consider various jamming behaviors, where jammers may attack all available channels with arbitrarily changing strategies over time, attack a subset of the channels at certain time slots, or have different intelligence, i.e., oblivious or adaptive adversary, and so on. Without any priori knowledge about the channels and jammers, it is very challenging to design an efficient and practical jamming-resistant SAA algorithm to reach the optimal EE goal. In this paper, we utilize the advanced martingale concentration inequalities in an multi-armed bandits-based online learning framework to facilitate the optimal detection of various jamming behaviors. We first define a novel EE model for discontiguous orthogonal frequency division multiplexing to facilitate scalable SAA over distributed spectrum pools in practice. Then, the jamming-resistant dynamic channel access problem is formulated as a regret minimization problem. Meanwhile, an online stochastic gradient descent with bandit feedback procedure is adopted to allocate the transmit power. The proposed algorithm can autonomously detect the environmental features and find a near-optimal solution in each attacking scenario. Our algorithm is implemented with low complexity and with multiple users under some practical jamming scenarios. Extensive numerical studies show that under some practical jamming scenarios, our algorithm has an EE improvement of 45.3% over a fixed learning period, and an improvement of 82.5% in terms of learning duration compared with existing approaches.