Miracle-dz/UniFAR-FTUs huggingface dataset:
Chemotherapy in elderly patients with nonsmall cell lung cancer

Purpose of review Using chemotherapy in elderly nonsmall cell lung cancer (NSCLC) patients is often challenging given concerns of treatment-related toxicity. However, data have demonstrated that chemotherapy can lead to improved survival in this age group. In this review, we summarize existing data and discuss the role of chemotherapy in elderly patients with localized, locally advanced, and metastatic NSCLC. Recent findings Clear evidence-based guidelines for chemotherapy management in elderly patients is lacking given the limited prospective data available. However, there are more clinical trials investigating optimal chemotherapy agents and dosing schedules specific to the elderly. Comprehensive geriatric assessment-directed interventions are also being prospectively investigated to improve treatment selection for elderly patients. Summary Chronological age should not be a limiting factor for chemotherapy use in elderly NSCLC patients. Several studies have demonstrated similar survival benefits than in younger patients when chemotherapy is given as adjuvant treatment for localized disease; part of definitive treatment with radiation in locally advanced disease; and palliative treatment for advanced NSCLC, however, at the cost of greater toxicity. Tolerability of chemotherapy in this heterogeneous group can be difficult to predict. Therefore, therapeutic decisions should be individualized based on performance status. Comprehensive geriatric assessment should be used to supplement performance status measures to minimize both under and overtreatment.
Cloning of the human kidney PAH transporter: narrow substrate specificity and regulation by protein kinase C.

Conserved from fish to mammals, renal proximal tubule organic anion secretion plays an important role in drug and xenobiotic elimination. Studies with the model substrate p-aminohippurate (PAH) have suggested that a basolateral PAH/α-ketoglutarate exchanger imports diverse organic substrates into the proximal tubule prior to apical secretion. cDNAs encoding PAH transporters have been cloned recently from rat and flounder. Here we report the cloning of a highly similar human PAH transporter (hPAHT) from human kidney. By Northern blot analysis and EST database searching, hPAHT mRNA was detected in kidney and brain. PCR-based monochromosomal somatic cell hybrid mapping placed the hPAHT gene on chromosome 11. When expressed transiently in vitro, hPAHT catalyzed time-dependent and saturable [3H]PAH uptake ( K m of ∼5 μM). Preincubation with unlabeled α-ketoglutaric or with glutaric acid stimulated tracer PAH uptake, and preincubation with unlabeled PAH stimulated tracer α-ketoglutarate uptake, results that are consistent with PAH/α-ketoglutarate exchange. Several structurally diverse organic anions cis-inhibited PAH uptake. Like rat OAT1 organic anion transporter, hPAHT was inhibited by furosemide, indomethacin, probenecid, and α-ketoglutarate. Unlike OAT1, hPAHT was not inhibited by prostaglandins or methotrexate (MTX). Moreover, tracer PGE2 and MTX were not transported, indicating that the substrate specificity for transport by hPAHT is not broad. PAH uptake was inhibited by phorbol 12-myristate 13-acetate (PMA) in a dose- and time-dependent fashion, but not by the inactive 4α-phorbol-12,13 didecanoate. PMA-induced inhibition was blocked by staurosporine. Thus the protein kinase C-mediated inhibition of basolateral organic anion entry previously reported in intact tubules is likely due, at least in part, to direct modulation of the PAH/α-ketoglutarate exchanger.
Differential spatial distribution of miR165/6 determines variability in plant root anatomy

ABSTRACT A clear example of interspecific variation is the number of root cortical layers in plants. The genetic mechanisms underlying this variability are poorly understood, partly because of the lack of a convenient model. Here, we demonstrate that Cardamine hirsuta, unlike Arabidopsis thaliana, has two cortical layers that are patterned during late embryogenesis. We show that a miR165/6-dependent distribution of the HOMEODOMAIN LEUCINE ZIPPER III (HD-ZIPIII) transcription factor PHABULOSA (PHB) controls this pattern. Our findings reveal that interspecies variation in miRNA distribution can determine differences in anatomy in plants. Highlighted Article: Comparison of the root patterning of Arabidopsis thaliana and Cardamine hirsuta reveals that species-specific cortical layering patterns are determined by the spatial distribution of microRNAs and their targets.
Excitation-contraction coupling in rat ventricular myocytes after formamide-induced detubulation.

Formamide-induced osmotic shock has been used to detubulate isolated adult rat ventricular myocytes (i.e., disrupt the surface membrane-T tubule junction). Cell volume, calculated from cell length and width, rapidly decreased and increased upon application and removal of formamide, respectively. After treatment with formamide, membrane capacitance decreased by 26.4% (from 199.4 ± 18.7 pF in control cells to 146.7 ± 6.4 pF in formamide-treated cells; n = 13, P < 0.05). However, the amplitude of the L-type Ca2+ current ( I Ca) decreased by a greater extent (from 0.75 ± 0.14 to 0.18 ± 0.03 nA; n = 5, P < 0.05) so that the density of I Ca decreased by 74.5%. Simultaneous measurements of I Ca and Ca2+ transients (monitored using fura 2) showed that both decreased rapidly upon removal of formamide. However, the Ca2+ content of the sarcoplasmic reticulum showed little change. Cross-striations, visualized with the fluorescent dye di-8-aminonaphthylethenylpyridinium, were sparse or absent in cells that had been treated with formamide, suggesting that formamide can successfully detubulate cardiac cells and that I Ca is concentrated in the T tubules, which therefore play an important role in excitation-contraction coupling.
EXTRACTING AUTOMATICALLY THE PERCEIVED INTENSITY OF MUSIC TITLES

We address the issue of extracting automatically hi gh-level musical descriptors out of their raw audio signal. This work focuses on the extraction of the perceived intensit y of music titles, that evaluates how energic the music is perceived b y listeners. We present here first the perceptive tests that we have conducted, in order to evaluate the relevance and the universa lity of the perceived intensity descriptor. Then we present se veral methods used to extract relevant features used to build aut omatic intensity extractors: usual Mpeg7 low level features, empiric al method, and features automatically found using our Extractor Di scovery System (EDS), and compare the final performances of their extractors.
Measurement of intracellular triglyceride stores by H spectroscopy: validation in vivo.

We validate the use of 1H magnetic resonance spectroscopy (MRS) to quantitatively differentiate between adipocyte and intracellular triglyceride (TG) stores by monitoring the TG methylene proton signals at 1.6 and 1.4 ppm, respectively. In two animal models of intracellular TG accumulation, intrahepatic and intramyocellular TG accumulation was confirmed histologically. Consistent with the histological changes, the methylene signal intensity at 1.4 ppm increased in both liver and muscle, whereas the signal at 1.6 ppm was unchanged. In response to induced fat accumulation, the TG concentration in liver derived from 1H MRS increased from 0 to 44.9 ± 13.2 μmol/g, and this was matched by increases measured biochemically (2.1 ± 1.1 to 46.1 ± 10.9 μmol/g). Supportive evidence that the methylene signal at 1.6 ppm in muscle is derived from investing interfascial adipose tissue was the finding that, in four subjects with generalized lipodystrophy, a disease characterized by absence of interfacial fat, no signal was detected at 1.6 ppm; however, a strong signal was seen at 1.4 ppm. An identical methylene chemical shift at 1.4 ppm was obtained in human subjects with fatty liver where the fat is located exclusively within hepatocytes. In experimental animals, there was a close correlation between hepatic TG content measured in vivo by 1H MRS and chemically by liver biopsy [ R = 0.934; P < . 0001; slope 0.98, confidence interval (CI) 0.70-1.17; y-intercept 0.26, CI -0.28 to 0.70]. When applied to human calf muscle, the coefficient of variation of the technique in measuring intramyocellular TG content was 11.8% in nonobese subjects and 7.9% in obese subjects and of extramyocellular (adipocyte) fat was 22.6 and 52.5%, respectively. This study demonstrates for the first time that noninvasive in vivo 1H MRS measurement of intracellular TG, including that within myocytes, is feasible at 1.5-T field strengths and is comparable in accuracy to biochemical measurement. In addition, in mixed tissue such as muscle, the method is clearly advantageous in differentiating between TG from contaminating adipose tissue compared with intramyocellular lipids.
Afferent arteriolar adenosine A 2a receptors are coupled to K ATP in in vitro perfused hydronephrotic rat kidney

Afferent arteriolar adenosine A 2a receptors are coupled to K ATP in in vitro perfused hydronephrotic rat kidney. Am. J. Physiol. 277 ( Renal Physiol. 46): F926–F933, 1999. —Adenosine is known to exert dual actions on the afferent arteriole, eliciting vasoconstriction, by activating A 1 receptors, and vasodilation at higher concentrations, by activating lower-affinity A 2 receptors. We could demonstrate both of these known adenosine responses in the in vitro perfused hydronephrotic rat kidney. Thus, 1.0 µM adenosine elicited a transient vasoconstriction blocked by 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), and 10–30 µM adenosine re- versed KCl-induced vasoconstriction. However, when we examined the effects of adenosine on pressure-induced afferent arteriolar vasoconstriction, we observed a third action. In this setting, a high-affinity adenosine vasodilatory response was observed at concentrations of 10–300 nM. This response was blocked by both 4-(2-[7-amino-2-(2-furyl)[1,2,4]triazolo[2,3- a][1,3,5]triazin-5-yl-amino]ethyl)phenol (ZM-241385) and glibenclamide and was mimicked by 2-phenylaminoadenosine (CV-1808) (IC 50 of 100 nM), implicating adenosine A 2a receptors coupled to ATP-sensitive K channels (K ATP ). Like adeno- sine, 5 8 - N -ethylcarboxamidoadenosine (NECA) elicited both glibenclamide-sensitive and glibenclamide-insensitive vasodi- latory responses. The order of potency for the glibenclamide-sensitive component was NECA . adenosine 5 CV-1808. Our ﬁndings suggest that, in addition to the previously described adenosine A 1 and low-affinity A 2b receptors, the renal micro- vasculature is also capable of expressing high-affinity adenosine A 2a receptors. This renal adenosine receptor elicits afferent arteriolar vasodilation at submicromolar adenosine levels by activating K ATP .
Role for parathyroid hormone in mechanical responsiveness of rat bone.

We investigated the relationship between parathyroid hormone (PTH) and mechanical stimulation in mechanically induced osteogenesis. In normal rats, mechanical stimulation of the eighth caudal vertebra induced an osteogenic response. This was augmented by a single injection of human PTH-(1-34) 30-45 min before loading. No osteogenic response was seen in thyroparathyroidectomized (TPTX) rats; the osteogenic response was restored by a single injection of PTH before stimulation, suggesting that physiological levels of PTH are necessary for the mechanical responsiveness of bone. c- fosexpression was detected only in the osteocytes of those rats that were both mechanically stimulated and given PTH. This suggests that PTH supports mechanically induced osteogenesis by sensitizing either the strain-sensing mechanism itself or early responses of bone to strain-generated signals. The osteogenic response was not augmented by two further daily injections of PTH and was not seen in TPTX rats in which PTH administration was started 3 days after loading. These results reveal a major role for PTH in the mechanical responsiveness of rat bone.
Equation to estimate resting energy expenditure in adolescents with sickle cell anemia.

BACKGROUND Basal energy requirements are higher in adolescents with sickle cell anemia (SCA) than in healthy control subjects. However, no equation is available to accurately predict their energy needs. OBJECTIVE Our objective was to develop a clinically useful equation to estimate resting energy expenditure (REE) in adolescents with SCA. DESIGN REE and other components of total energy expenditure were measured in adolescents with SCA (n = 37) and in control subjects (n = 23) for 24 h in a whole-room indirect calorimeter. Multiple linear regression analysis was used to describe the relations of REE with independent variables such as sex, weight, height, fat-free mass, fat mass, age, and hemoglobin concentration in adolescents with SCA. The Bland-Altman comparison technique was used to compare values predicted by existing equations with measured REE values. RESULTS Mean (+/-SD) measured REEs were 7746 +/- 974 and 6332 +/- 869 kJ/d in the male and female subjects with SCA, respectively, and these values were 16% higher than those in the healthy control subjects. Standard equations underestimated REE by 12% (P </= 0.001) in adolescents with SCA and overestimated REE by 4% in control subjects (P = 0.01-0.29). Several REE regression equations for SCA were developed. The most parsimonious equation for males was REE (kJ/d) = 5461 + 77.7. weight (kg) - 233.2. hemoglobin (g/dL), or REE (kcal/d) = 1305 + 18.6. weight (kg) - 55.7. hemoglobin (g/dL). For females, the most parsimonious equation was REE (kJ/d) = 4603 + 55.6. weight (kg) - 126.2. hemoglobin (g/dL), or REE (kcal/d) = 1100 + 13.3. weight (kg) - 30.2. hemoglobin (g/dL). CONCLUSION The new equations have better agreement with the basal metabolic needs of adolescents with SCA than do standard predictive equations.
Online Barycenter Estimation of Large Weighted Graphs

In this paper, we propose a new method to compute the barycenter of large weighted graphs endowed with probability measures on their nodes. We suppose that the edge weights are distances between the nodes and that the probability measure on the nodes is related to events observed there. For instance, a graph can represent a subway network: its edge weights are the distance between two stations, and the observed events at each node are the subway users getting in or leaving the subway network at this station. The probability measure on the nodes does not need to be explicitly known. Our strategy only uses observed node related events to give more or less emphasis to the different nodes. Furthermore, the barycenter estimation can be updated in real time with each new event. We propose a multiscale extension of \cite{arXiv:1605.04148} where the decribed strategy is valid only for medium-sized graphs due to memory costs. Our multiscale approach is inspired from the geometrical decomposition of the barycenter in a Euclidean space: we apply a heuristic \textit{divide et impera} strategy based on a preliminary clustering. Our strategy is finally assessed on road- and social-networks of up to $10^6$ nodes. We show that its results compare well with \cite{arXiv:1605.04148} in terms of accuracy and stability on small graphs, and that it can additionally be used on large graphs even on standard laptops.
Garlic consumption and cancer prevention: meta-analyses of colorectal and stomach cancers.

BACKGROUND Animal and in vitro studies have provided evidence of an anticarcinogenic effect of active ingredients in garlic. OBJECTIVE The objective was to conduct meta-analyses of the epidemiologic literature on the association between garlic consumption and risk of stomach, colon, head and neck, lung, breast, and prostate cancers. DESIGN Meta-analyses were conducted for all cancers mutually and separately for colorectal and stomach cancers in relation to consumption of exclusively raw garlic, cooked garlic, or both (RC garlic). Eighteen studies reported a relative risk estimate for RC garlic consumption and cancer risk. RESULTS In the meta-analyses of colorectal and stomach cancer, the reference categories ranged from no consumption to consumption of 3.5 g/wk, whereas the highest categories ranged from any consumption to >28.8 g/wk. The average difference between the highest and lowest categories was 16 g/wk. The random-effects relative risk (RR) estimate of colorectal cancer and RC garlic consumption, excluding garlic supplements, was 0.69 (95% CI: 0.55, 0.89). For stomach cancer, the random-effects RR estimate was 0.53 (95% CI: 0.31, 0.92). The heterogeneity among studies for the latter outcome (P: = 0.0002) indicates the questionableness of the generalizability of this summary estimate. An indication of publication bias for all cancers combined is evident from a funnel plot of RC garlic consumption and cancer risk and from the results of the Begg and Mazumdar test (P: = 0.049). CONCLUSIONS High intake of RC garlic may be associated with a protective effect against stomach and colorectal cancers. Heterogeneity of effect estimates, differences in dose estimation, publication bias, and possible alternative hypotheses (eg, confounding by total vegetable consumption) preclude sole reliance on summary effect estimates.
Nutritional indicators of adverse pregnancy outcomes and mother-to-child transmission of HIV among HIV-infected women.

BACKGROUND Poor nutrition may be associated with mother-to-child transmission (MTCT) of HIV and other adverse pregnancy outcomes. OBJECTIVE The objective was to examine the relation of nutritional indicators with adverse pregnancy outcomes among HIV-infected women in Tanzania, Zambia, and Malawi. DESIGN Body mass index (BMI; in kg/m(2)) and hemoglobin concentrations at enrollment and weight change during pregnancy were prospectively related to fetal loss, neonatal death, low birth weight, preterm birth, and MTCT of HIV. RESULTS In a multivariate analysis, having a BMI < 21.8 was significantly associated with preterm birth [odds ratio (OR): 1.82; 95% CI: 1.34, 2.46] and low birth weight (OR: 2.09; 95% CI: 1.41, 3.08). A U-shaped relation between weight change during pregnancy and preterm birth was observed. Severe anemia was significantly associated with fetal loss or stillbirth (OR: 3.67; 95% CI: 1.16, 11.66), preterm birth (OR: 2.08; 95% CI: 1.39, 3.10), low birth weight (OR: 1.76; 95% CI: 1.07, 2.90), and MTCT of HIV by the time of birth (OR: 2.26; 95% CI: 1.18, 4.34) and by 4-6 wk among those negative at birth (OR: 2.33; 95% CI: 1.15, 4.73). CONCLUSIONS Anemia, poor weight gain during pregnancy, and low BMI in HIV-infected pregnant women are associated with increased risks of adverse infant outcomes and MTCT of HIV. Interventions that reduce the risk of wasting or anemia during pregnancy should be evaluated to determine their possible effect on the incidence of adverse pregnancy outcomes and MTCT of HIV.
Dietary peptides increase endogenous amino acid losses from the gut in adults.

BACKGROUND Accurate estimates of endogenous ileal total nitrogen and amino acid flows are necessary to ascertain true dietary amino acid digestibility coefficients and for the factorial estimation of dietary amino acid requirements. OBJECTIVE The objective was to ascertain endogenous amino acid losses from the small bowel in human subjects consuming a protein-free diet or a diet with enzyme-hydrolyzed casein (EHC; MW <5000) as the sole source of nitrogen. DESIGN The subjects were 8 men and women with terminal ileum ileostomies after ulcerative colitis who consumed the protein-free and EHC-based diets in a crossover design. Each subject received each test diet in single meals followed by 2 consecutive 9-h total collections of digesta. Digesta samples for the EHC treatment were centrifuged and ultrafiltered (10 000 MW cutoff), with the precipitate-plus-retentate fraction (>10 000 MW) providing a measurement of endogenous ileal amino acids. RESULTS The mean endogenous flows for most of the amino acids and nitrogen were significantly (P < 0.05) higher when determined with the EHC-based diet than with the protein-free diet. Mean (n = 8) endogenous ileal nitrogen flows were 2061 and 4233 mug/g dry matter intake for the protein-free and EHC-based diets, respectively. CONCLUSION The traditional protein-free method underestimates endogenous ileal amino acid loss in adults.
Electrical properties of ZnO single nanowires contacted by FIBID and EBL

Semiconductor nanowires are used for building electronic devices like chemical or biological sensors, nwFETs, memories, light emitting diodes. In order to properly use the nanowires for such applications, the understanding of the transport properties in this kind of nanostructures becomes more and more important. To our knowledge, there is no evidence in the literature of the electrical properties of single zinc oxide nanowires grown electrochemically. In this paper we investigate the electrical properties of ZnO nanowires grown electrochemically by the template method (1). Contacting a single nanowire was a barrier that has been overcome using different lithographic techniques. Interdigitated electrodes made from different materials (Pt, Al) were deposited on Si/SiO2 substrates using photolithography combined with thermal vacuum evaporation. The contact between the nanowire and the interdigitated electrodes was made by e-beam lithography (EBL) and by focused ion beam induced deposition (FIBID) of platinum stripes. The quantitative analysis of the current-voltage measurements gave us information about the intrinsic parameters of the ZnO nanowires such as conductivity, mobility or concentration of impurities. By fitting the curves using the metal-semiconductor-metal (M-S-M) model (2) the effective potential barrier was computed. A comparison between the two methods of contacting the semiconducting nanowires was made in order to select the one that is most suitable for being used in applications. Our results are comparable with electrical measurements made on ZnO nanowires prepared by other methods such as high-temperature thermal evaporation process (3), vapor-liquid-solid process (4, 5) or electric field assisted nucleation (6).
From granuloma to fibrosis: sarcoidosis associated pulmonary fibrosis

Purpose of review Up to twenty percent of patients with sarcoidosis develop pulmonary fibrosis, transforming an often benign disease into a highly morbid and potentially fatal one. We highlight the fibrotic pulmonary sarcoidosis phenotype as an area of intense clinical and translational investigation, review recent developments in treatment, and provide a roadmap for future research in sarcoidosis associated pulmonary fibrosis. Recent findings Granulomatous inflammation in a lymphatic distribution is the hallmark finding of pulmonary sarcoidosis and the nidus for fibrosis. Recent research demonstrates that fibrotic sarcoidosis begins in the setting of persistent, uncontrolled inflammation, and is aided by pro-fibrotic genetic features and immune responses. Comparison to other fibrotic lung diseases also reveals key features that inform our understanding of common pathways in fibrosis. Summary Understanding the mechanisms of fibrotic transformation in sarcoidosis enhances clinical care and facilitates development of novel therapeutic options. The impact of these findings in fibrotic sarcoidosis may be amplified through application to other interstitial lung diseases marked by inflammatory to fibrotic transformation. Important aspects of clinical management of fibrotic sarcoidosis include surveillance for co-morbidities, such as pulmonary hypertension, airway disease, and infection, and assessment for pulmonary disease activity that may benefit from immunosuppression.