Miracle-dz/UniFAR-FTUs huggingface dataset:
Sequential Everolimus and Sunitinib Treatment in Pancreatic Metastatic Well-Differentiated Neuroendocrine Tumours Resistant to Prior Treatments

Objective: Alternating treatment with sunitinib and everolimus has been shown to be efficacious in renal cell carcinoma. However, no data currently exist for the role of alternate sequence administration of these agents in well-differentiated pancreatic neuroendocrine tumours (pNETs). Methods: Thirty-one patients were administered one compound and upon progression were switched to the other. All patients had grade 1 or 2 tumours and stage IV disease with similar metastatic load. The primary end point included estimation of the median overall progression-free survival (mPFS) along with each drug's mPFS as a first-line (mPFS1) and a second-line treatment (mPFS2); tolerability and serious adverse events were also evaluated. Secondary end points included overall survival (OS), 2-year mortality rate, and incidence of disease progression. Results: Overall, mPFS did not differ between the everolimus to sunitinib group (36.5 months) and the sunitinib to everolimus group (31.6 months) with a hazard ratio of 0.94 ([95% CI, 0.45-1.97], p = 0.7). Although mPFS1 after first-line everolimus was longer (16.3 months) compared to sunitinib (9 months), this was not statistically significant (p = 0.15). Sequential second-line treatment showed no difference in the mPFS2 (p = 0.3). No difference in OS between the 2 groups was observed. Tolerability was better for everolimus compared to sunitinib. Conclusions: Treatment with sequential molecular target agents was well tolerated and associated with similar overall mPFS in both schemes of administration. Larger prospective studies are required to investigate the long-term efficacy and sequence of administration of alternate therapy with molecular targeting agents in metastatic pNETs and their effect on OS.
Indexing based on scale invariant interest points

This paper presents a new method for detecting scale invariant interest points. The method is based on two recent results on scale space: (1) Interest points can be adapted to scale and give repeatable results (geometrically stable). (2) Local extrema over scale of normalized derivatives indicate the presence of characteristic local structures. Our method first computes a multi-scale representation for the Harris interest point detector. We then select points at which a local measure (the Laplacian) is maximal over scales. This allows a selection of distinctive points for which the characteristic scale is known. These points are invariant to scale, rotation and translation as well as robust to illumination changes and limited changes of viewpoint. For indexing, the image is characterized by a set of scale invariant points; the scale associated with each point allows the computation of a scale invariant descriptor. Our descriptors are, in addition, invariant to image rotation, of affine illumination changes and robust to small perspective deformations. Experimental results for indexing show an excellent performance up to a scale factor of 4 for a database with more than 5000 images.
The α2δ-1 subunit remodels CaV1.2 voltage sensors and allows Ca2+ influx at physiological membrane potentials

Voltage-sensing domains (VSDs) in voltage-gated calcium channels sense the potential difference across membranes and interact with the pore to open it. Savalli et al. find that the accessory subunit α2δ-1 increases the sensitivity of VSDs I–III and also their efficiency of coupling to the pore.
The RANKL/RANK/OPG Signaling Pathway Mediates Medial Arterial Calcification in Diabetic Charcot Neuroarthropathy

OBJECTIVE The receptor activator of nuclear factor-κB (RANK), RANK ligand (RANKL), and osteoprotegerin (OPG) signaling pathway (RANKL/RANK/OPG signaling) is implicated in the osteolysis associated with diabetic Charcot neuroarthropathy (CN); however, the links with medial arterial calcification (MAC) seen in people with CN are unclear. This study aimed to investigate the role of RANKL/OPG in MAC in patients with CN. RESEARCH DESIGN AND METHODS Enzyme-linked immunosorbent assay and Bio-plex multiarray technology were used to quantify a range of cytokines, including RANKL and OPG in sera from 10 patients with diabetes, 12 patients with CN, and 5 healthy volunteers. Human tibial artery segments were immunohistochemically stained with Alizarin red and human RANKL antibody. Human vascular smooth muscle cells (VSMCs) were also explanted from arterial segments for in vitro studies. RESULTS We demonstrate colocalization and upregulation of RANKL expression in areas displaying MAC. Systemic levels of RANKL, OPG, and inflammatory cytokines (interleukin-8, granulocyte colony–stimulating factor) were elevated in those with CN compared with diabetic patients and healthy control subjects. Human VSMCs cultured in CN serum showed accelerated osteoblastic differentiation (alkaline phosphatase activity) and mineralization (alizarin red staining) compared with cells treated with diabetic or control serum (P < 0.05). Coincubation with OPG, the decoy receptor for RANKL, attenuated osteogenic differentiation of VSMCs and was independent of a high calcium-phosphate milieu. The accelerated mineralization induced by RANKL and CN serum correlated with nuclear translocation of nuclear factor-κB, a process abrogated by OPG. CONCLUSIONS Our data provide direct evidence that RANKL/RANK/OPG signaling is modulated in patients with CN and plays a role in vascular calcification. This study highlights this pathway as a potential target for intervention.
Geostrophic and ageostrophic circulation of a shallow anticyclonic eddy off Cape Bojador

A shallow mesoscale anticyclonic eddy, observed south of the Canary Islands with satellite altimetry, has been intensively studied with multiparametric sampling. Hydrographic data from a CTD installed on an undulating Nu-shuttle platform reveal the presence of a mesoscale anticyclonic eddy of ∼125 km diameter. The difference in sea level anomaly (SLA) between the interior and the edge of the eddy, as determined from altimetry, is ∼15 cm, which compares well with the maximum dynamic height differences as inferred using a very shallow reference level (130 m). Further, the associated surface geostrophic velocities, of about 35 cm s−1 in the northeast and southwest edges of the eddy, are in good agreement with direct velocity measurements from the ship. Deep rosette-CTD casts confirm that the structure is a shallow eddy extending no deeper than 250 m before the fusion with another anticyclone. The SLA-tendency (temporal rate of change of sea surface height) indicates a clear northwestward migration during the two first weeks of November 2008. Applying an eddy SSH-based tracker, the eddy's velocity propagation is estimated as 4 km d−1. Use of the QG-Omega equation diagnoses maximum downward/upward velocities of about ±2 m d−1. The instability of the Canary coastal jet appears to be the mechanism responsible for the generation of the shallow anticyclonic eddy.
Journal of Cerebral Blood Flow and Metabolism Mild Cerebral Hypothermia during and after Cardiac Arrest Improves Neurologic Outcome in Dogs

We previously found mild hypothermia (34-36°C), induced before cardiac arrest, to improve neu­ rologic outcome. In this study we used a reproducible dog model to evaluate mild hypothermia by head cooling dur­ ing arrest, continued with systemic cooling (34°C) during recirculation and for 1 h after arrest. In four groups of dogs, ventricular fibrillation (no flow) of 12.5 min at 37 SC was reversed with cardiopulmonary bypass and defibrillation in �5 min, and followed by controlled ven­ tilation to 20 h and intensive care to 96 h. In Study A we resuscitated with normotension and normal hematocrit; Control Group A-I (n = 12) was maintained normother­ mic, while Treatment Group A-II (n = 10) was treated with hypothermia. In Study B we resuscitated with hy­ pertension and hemodilution. Control Group B-1 (n = 12) was maintained normothermic (6 of 12 were not hemodi­ luted), while Treatment Group B-II (n = 10) was treated with hypothermia. Best overall performance categories This study concerns two relatively unexplored concepts: (a) hypothermia initiated during ischemia (preservation) and continued after ischemia (resus­ citation) in contrast to hypothermia initiated before ischemia (protection), which is known to mitigate postischemic brain damage (Bigelow et aI. , 1950; Rupp and Severinghaus, 1986); (b) mild hypother­ mia (temperature 34-36°C) in contrast to moderate hypothermia (28-32°C), which is known to protect the brain (Bigelow et aI. , 1950) and may be harmful. and OPC 3 or 4 in 0 dogs. Mean neurologic deficit and brain histopathologic damage scores showed similar sig­ nificant group differences. Morphologic myocardial dam­ age scores were the same in all four groups. We conclude that mild brain cooling during and after insult improves neurologic outcome after cardiac arrest. circulatory arrest including complete global brain ischemia with no flow) (Safar, 1986) reversed by cardiopulmonary-cerebral resuscitation (Safar and Bircher, 1988)-not incomplete global brain isch­ emia (e. g. , shock), incomplete focal ischemia (stroke), or cerebral trauma. on focal ischemia and brain contusion suggested benefit also from moderate postinsult cooling (Rosomoff, 1959; Rosomoff et aI. , 1960). Hypother­ mia research was almost given up, however, be­ cause of management problems such as shivering,
Do visualizations improve synchronous remote collaboration?

Information visualizations can improve collaborative problem solving, but this improvement may depend on whether visualizations promote communication. In an experiment on the effect of network visualizations, remote pairs worked synchronously to identify a serial killer. They discussed disparate evidence distributed across the pair using IM. Four conditions, respectively, offered (a) spreadsheet only (controls), (b) individual unshared visualizations, (c) view-only shared visualizations, and (d) a full-access shared visualization of all evidence. We examined collaborative performance, use of the visualization tool, and communication as a function of condition. All visualization conditions improved remote collaborators' performance over the control condition. Full access to a shared visualization best facilitated remote collaboration by encouraging tool use and fostering discussion between the partners. Shared visualization without full access impaired performance somewhat and made communication even more vital to identifying the serial killer. This study provides direct evidence of visualization tool features and partner behavior that promote collaboration.
The Support of a Recognizable Series over a Zero-sum Free, Commutative Semiring is Recognizable

We show that the support of a recognizable series over a zero-sum free, commutative semiring is a recognizable language. We also give a sufficient and necessary condition for the existence of an effective transformation of a weighted automaton recognizing a series S over a zero-sum free, commutative semiring into an automaton recognizing the support of S.
Monolithically Integrated III-Sb-Based Laser Diodes Grown on Miscut Si Substrates

We report the formation and growth characteristics of an interfacial misfit (IMF) array between AlSb and Si and its application to III-Sb-based quantum-well broad-area edge-emitting laser diodes monolithically grown on an Si (001) substrate. A 13% lattice mismatch between AlSb and Si is accommodated by using the IMF array. A use of 5deg miscut Si substrates enables simultaneous IMF formation and suppression of an antiphase domain, resulting in a drastic suppression of dislocation density over the III-Sb epilayer and realization of electrically injected laser diodes operating at 77 K. The current-voltage characteristics indicate a diode turn-on of 0.7 V, which is consistent with a theoretical built-in potential of the laser diode. This device is characterized by a 9.1-Omega forward resistance and a leakage current density of 0.7 A/cm2 at -5 V and 46.9 A/cm2 at -15 V.
Characterization of the platelet transcriptome by RNA sequencing in patients with acute myocardial infarction

Abstract Transcripts in platelets are largely produced in precursor megakaryocytes but remain physiologically active as platelets translate RNAs and regulate protein/RNA levels. Recent studies using transcriptome sequencing (RNA-seq) characterized the platelet transcriptome in limited number of non-diseased individuals. Here, we expand upon these RNA-seq studies by completing RNA-seq in platelets from 32 patients with acute myocardial infarction (MI). Our goals were to characterize the platelet transcriptome using a population of patients with acute MI and relate gene expression to platelet aggregation measures and ST-segment elevation MI (STEMI) (n = 16) vs. non-STEMI (NSTEMI) (n = 16) subtypes. Similar to other studies, we detected 9565 expressed transcripts, including several known platelet-enriched markers (e.g. PPBP, OST4). Our RNA-seq data strongly correlated with independently ascertained platelet expression data and showed enrichment for platelet-related pathways (e.g. wound response, hemostasis, and platelet activation), as well as actin-related and post-transcriptional processes. Several transcripts displayed suggestively higher (FBXL4, ECHDC3, KCNE1, TAOK2, AURKB, ERG, and FKBP5) and lower (MIAT, PVRL3, and PZP) expression in STEMI platelets compared to NSTEMI. We also identified transcripts correlated with platelet aggregation to TRAP (ATP6V1G2, SLC2A3), collagen (CEACAM1, ITGA2), and ADP (PDGFB, PDGFC, ST3GAL6). Our study adds to current platelet gene expression resources by providing transcriptome-wide analyses in platelets isolated from patients with acute MI. In concert with prior studies, we identify various genes for further study in regards to platelet function and acute MI. Future platelet RNA-seq studies examining more diverse sets of healthy and diseased samples will add to our understanding of platelet thrombotic and non-thrombotic functions.
Excessive Exercise Habits in Marathoners as Novel Indicators of Masked Hypertension

Background. Excessive exercise such as marathon running increases the risk of cardiovascular events that may be related to myocardial infarction and sudden death. We aimed to investigate that the exercise characteristics can be used as a novel indicator of masked hypertension. Methods. A total of 571 middle-aged recreational male marathoners were assigned to a high blood pressure group (HBPG; n = 214) or a normal blood pressure group (NBPG; n = 357). A graded exercise test was used to examine the hemodynamic response and cardiac events, and the personal exercise characteristics were recorded. Results. Systolic blood pressure and diastolic blood pressure were higher in the HBPG than in the NBPG (p < 0.05, all). The marathon history, exercise intensity, and time were longer and higher, whereas the marathon completion duration was shorter in the HBPG than in NBPG (p < 0.05, all). HBPG showed a higher frequency of alcohol consumption than NBPG (p < 0.05). Conclusion. More excessive exercise characteristics than the normative individuals. If the individuals exhibit high blood pressure during rest as well as exercise, the exercise characteristics could be used as a novel indicator for masked hypertension.
Impacts of environmental factors on fine root lifespan

The lifespan of fast-cycling roots is a critical parameter determining a large flux of plant carbon into soil through root turnover and is a biological feature regulating the capacity of a plant to capture soil water and nutrients via root-age-related physiological processes. While the importance of root lifespan to whole-plant and ecosystem processes is increasingly recognized, robust descriptions of this dynamic process and its response to changes in climatic and edaphic factors are lacking. Here we synthesize available information and propose testable hypotheses using conceptual models to describe how changes in temperature, water, nitrogen (N), and phosphorus (P) availability impact fine root lifespan within a species. Each model is based on intrinsic responses including root physiological activity and alteration of carbohydrate allocation at the whole-plant level as well as extrinsic factors including mycorrhizal fungi and pressure from pathogens, herbivores, and other microbes. Simplifying interactions among these factors, we propose three general principles describing fine root responses to complex environmental gradients. First, increases in a factor that strongly constrains plant growth (temperature, water, N, or P) should result in increased fine root lifespan. Second, increases in a factor that exceeds plant demand or tolerance should result in decreased lifespan. Third, as multiple factors interact fine root responses should be determined by the most dominant factor controlling plant growth. Moving forward, field experiments should determine which types of species (e.g., coarse vs. fine rooted, obligate vs. facultative mycotrophs) will express greater plasticity in response to environmental gradients while ecosystem models may begin to incorporate more detailed descriptions of root lifespan and turnover. Together these efforts will improve quantitative understanding of root dynamics and help to identify areas where future research should be focused.
Effects of the Selective Aldosterone Blocker Eplerenone Versus the Calcium Antagonist Amlodipine in Systolic Hypertension

Abstract—Eplerenone is a highly selective aldosterone blocker, which is under development for the treatment of hypertension and heart failure. To assess its usefulness in older patients with systolic hypertension and widened pulse pressure, we compared the effects of eplerenone with amlodipine, on clinic blood pressure (BP) and pulse pressure and in a subset of the patients, ambulatory BP, vascular compliance, and urinary albumin excretion. The study involved 269 patients ≥50 years of age who were randomly assigned to either eplerenone (50 to 200 mg daily) or amlodipine (2.5 to 10 mg daily) in a double-blind titration to effect design. After 24 weeks of therapy, reductions in clinic systolic BP were similar for both treatments (eplerenone, −20.5±1.1 mm Hg; amlodipine, −20.1±1.1 mm Hg). Reductions in clinic diastolic BP were modestly larger on amlodipine (−6.9±0.7 mm Hg) compared with eplerenone (−4.5±0.7 mm Hg) (P =0.014). Pulse pressure was also reduced similarly from baseline by the 2 treatment groups (eplerenone, −15.9 mm Hg versus amlodipine, −13.4 mm Hg, P =0.07). Changes from baseline in pulse wave velocity after 24 weeks of therapy were statistically similar for eplerenone and amlodipine. In patients with microalbuminuria at baseline (>30 mg albumin/g creatinine), eplerenone reduced the urinary albumin/creatinine ratio by 52% compared with a reduction of 10% by amlodipine (P =0.04). Thus, eplerenone was as effective as amlodipine in lowering systolic BP and pulse pressure as well as pulse wave velocity in older patients with widened pulse pressure hypertension. Furthermore, eplerenone reduced microalbuminuria to a greater extent than amlodipine in this older patient group.
Prevalence of Knee Pain and Its Influence on Quality of Life and Physical Function in the Korean Elderly Population: A Community Based Cross-Sectional Study

To investigate the prevalence of knee pain and its influence on physical function and quality of life (QOL), we examined 504 community residents of Chuncheon, aged ≥ 50 yr. Demographic information was obtained by questionnaire, and radiographic evaluations consisted of weight-bearing semi-flexed knee anteroposterior radiographs. Self-reported QOL and function were assessed using the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index and Short Form 12 (SF-12). Performance-based lower extremity function was assessed using the tests consisting of standing balance, usual walk and chair stands. The prevalence of knee pain was 46.2% (32.2% in men and 58.0% in women) and increased with age in women. After adjustment of confounders including the presence of knee OA, the subjects with knee pain had significantly worse WOMAC function and SF-12 scores compared to subjects without knee pain. Among the subjects with knee pain, women had worse WOMAC and SF-12 scores than men. Subjects with knee pain had worse physical performance score compared to those without knee pain, especially among females. In conclusion, the prevalence of knee pain is high (32.2% in men and 58.0% in women) in this elderly community population in Korea. Independent of knee OA and other confounding factors, subjects with knee pain have more than 5-fold increase in the risk of belonging to the worst lower extremity function compared to subjects without knee pain.
Ocular manifestations in children born after in vitro fertilization.

OBJECTIVE To report the ocular abnormalities found in children born after in vitro fertilization. METHODS Forty-seven children (25 girls and 22 boys) born after an in vitro fertilization pregnancy (mean +/- SD birth weight, 2335 +/- 817 g; range, 924-4300 g) and referred for ophthalmic evaluation were included in the study. All underwent a thorough ocular examination. Obstetric history was gathered following a detailed questionnaire with the mothers. RESULTS Of 70 eyes among nonverbal children, visual acuity was "normal for age" in 60 (86%), "fair" in 4 (6%), and "poor" in 6 (9%). Visual acuity in 24 eyes in verbal children ranged from 6/6 to no light perception, with 4 (17%) having poor vision. Cycloplegic refraction disclosed an emmetropia in 22 (27%), hypermetropia in 47 (57%), and myopia in 13 (16%) of the eyes. Anisometropia of more than 1.0 diopters was found in 8 children. Major ocular malformations were observed in 12 (26%) of the 47 children. These malformations included Coats disease, congenital cataract, congenital glaucoma, hypoplastic optic nerve head, idiopathic optic atrophy, coloboma with microphthalmos, and retinoblastoma. CONCLUSIONS Ocular anomalies were frequently observed in this cohort of offspring born after in vitro fertilization. A diligent and prospective prenatal search for such malformations should unveil the real prevalence of ocular malformations in children born after in vitro fertilization.