Miracle-dz/UniFAR-FTUs huggingface dataset:
Glutamine Transporters Are Targets of Multiple Oncogenic Signaling Pathways in Prostate Cancer

Despite the known importance of androgen receptor (AR) signaling in prostate cancer, the processes downstream of AR that drive disease development and progression remain poorly understood. This knowledge gap has thus limited the ability to treat cancer. Here, it is demonstrated that androgens increase the metabolism of glutamine in prostate cancer cells. This metabolism was required for maximal cell growth under conditions of serum starvation. Mechanistically, AR signaling promoted glutamine metabolism by increasing the expression of the glutamine transporters SLC1A4 and SLC1A5, genes commonly overexpressed in prostate cancer. Correspondingly, gene expression signatures of AR activity correlated with SLC1A4 and SLC1A5 mRNA levels in clinical cohorts. Interestingly, MYC, a canonical oncogene in prostate cancer and previously described master regulator of glutamine metabolism, was only a context-dependent regulator of SLC1A4 and SLC1A5 levels, being unable to regulate either transporter in PTEN wild-type cells. In contrast, rapamycin was able to decrease the androgen-mediated expression of SLC1A4 and SLC1A5 independent of PTEN status, indicating that mTOR complex 1 (mTORC1) was needed for maximal AR-mediated glutamine uptake and prostate cancer cell growth. Taken together, these data indicate that three well-established oncogenic drivers (AR, MYC, and mTOR) function by converging to collectively increase the expression of glutamine transporters, thereby promoting glutamine uptake and subsequent prostate cancer cell growth. Implications: AR, MYC, and mTOR converge to increase glutamine uptake and metabolism in prostate cancer through increasing the levels of glutamine transporters. Mol Cancer Res; 15(8); 1017–28. ©2017 AACR.
The Important Role for Intravenous Iron in Perioperative Patient Blood Management in Major Abdominal Surgery

Objective: To determine if preoperative intravenous (IV) iron improves outcomes in abdominal surgery patients. Summary Background Data: Preoperative iron deficiency anemia (IDA) occurs frequently; however if left untreated, increases the risk of blood transfusion allogeneic blood transfusion (ABT). Limited evidence supports IDA treatment with preoperative IV iron. This randomized controlled trial aimed to determine whether perioperative IV iron reduced the need for ABT. Methods: Between August 2011 and November 2014, 72 patients with IDA were assigned to receive either IV iron or usual care. The primary endpoint was incidence of ABT. Secondary endpoints were various hemoglobin (Hb) levels, change in Hb between time points, length of stay, iron status, morbidity, mortality, and quality of life 4 weeks postsurgery. Results: A 60% reduction in ABT was observed in the IV iron group compared with the usual care group (31.25% vs 12.5%). Hb values, although similar at randomization, improved by 0.8 g/dL with IV iron compared with 0.1 g/dL with usual care (P = 0.01) by the day of admission. The IV iron group had higher Hb 4 weeks after discharge compared with the usual care group (1.9 vs 0.9 g/dL, P = 0.01), and a shorter length of stay (7.0 vs 9.7 d, P = 0.026). There was no difference in discharge Hb levels, morbidity, mortality, or quality of life. Conclusions: Administration of perioperative IV iron reduces the need for blood transfusion, and is associated with a shorter hospital stay, enhanced restoration of iron stores, and a higher mean Hb concentration 4 weeks after surgery.
The effect of maximal rate codes on the interfering message rate

It is shown that, for a subset of input distributions, the effect of maximum rate transmission on an additional transmitted message, over the additive Gaussian noise channel, is, effectively, that of an additional additive Gaussian noise. Meaning, that the behavior of the mutual information and minimum mean-square error are as if additional additive Gaussian noise were transmitted. Such an observation provides corner points of the two-user Gaussian interference channel, for this subset.
Quantifying the influence of global warming on unprecedented extreme climate events

Significance Extreme climate events have increased in many regions. Efforts to test the influence of global warming on individual events have also increased, raising the possibility of operational, real-time, single-event attribution. We apply four attribution metrics to four climate variables at each available point on a global grid. We find that historical global warming has increased the severity and probability of the hottest monthly and daily events at more than 80% of the observed area and has increased the probability of the driest and wettest events at approximately half of the observed area. Our results suggest that scientifically durable operational attribution is possible but they also highlight the importance of carefully diagnosing and testing the physical causes of individual events. Efforts to understand the influence of historical global warming on individual extreme climate events have increased over the past decade. However, despite substantial progress, events that are unprecedented in the local observational record remain a persistent challenge. Leveraging observations and a large climate model ensemble, we quantify uncertainty in the influence of global warming on the severity and probability of the historically hottest month, hottest day, driest year, and wettest 5-d period for different areas of the globe. We find that historical warming has increased the severity and probability of the hottest month and hottest day of the year at >80% of the available observational area. Our framework also suggests that the historical climate forcing has increased the probability of the driest year and wettest 5-d period at 57% and 41% of the observed area, respectively, although we note important caveats. For the most protracted hot and dry events, the strongest and most widespread contributions of anthropogenic climate forcing occur in the tropics, including increases in probability of at least a factor of 4 for the hottest month and at least a factor of 2 for the driest year. We also demonstrate the ability of our framework to systematically evaluate the role of dynamic and thermodynamic factors such as atmospheric circulation patterns and atmospheric water vapor, and find extremely high statistical confidence that anthropogenic forcing increased the probability of record-low Arctic sea ice extent.
Multilocus analysis reveals three candidate genes for Chinese migraine susceptibility

Several genome‐wide association studies (GWASs) in Caucasian populations have identified 12 loci that are significantly associated with migraine. More evidence suggests that serotonin receptors are also involved in migraine pathophysiology. In the present study, a case–control study was conducted in a cohort of 581 migraine cases and 533 ethnically matched controls among a Chinese population. Eighteen polymorphisms from serotonin receptors and GWASs were selected, and genotyping was performed using a Sequenom MALDI‐TOF mass spectrometry iPLEX platform. The genotypic and allelic distributions of MEF2D rs2274316 and ASTN2 rs6478241 were significantly different between migraine patients and controls. Univariate and multivariate analysis revealed significant associations of polymorphisms in the MEF2D and ASTN2 genes with migraine susceptibility. MEF2D, PRDM16 and ASTN2 were also found to be associated with migraine without aura (MO) and migraine with family history. And, MEF2D and ASTN2 also served as genetic risk factors for the migraine without family history. The generalized multifactor dimensionality reduction analysis identified that MEF2D and HTR2E constituted the two‐factor interaction model. Our study suggests that the MEF2D, PRDM16 and ASTN2 genes from GWAS are associated with migraine susceptibility, especially MO, among Chinese patients. It appears that there is no association with serotonin receptor related genes.
Mobile phone text messaging to improve knowledge and practice of diabetic foot care in a developing country: Feasibility and outcomes.

PURPOSE To test the feasibility and effectiveness of using mobile phone text messaging to reinforce learning and the practice of diabetic foot care in a developing country. METHODS Ongoing learning reinforcement (2-3 times weekly) by text messaging followed an informal class on diabetic foot care in a community clinic setting. Subjects with cell phone access and no history of diabetic foot wounds or current wounds were recruited for participation (N = 225). Foot examinations and pretesting by survey occurred just before patients departed the clinic; the posttest survey and a final foot examination occurred 12 weeks later. The survey included basic demographic items along with items to measure knowledge and current foot care practices. One sample t tests (raw scores) and Wilcoxon signed-rank tests compared knowledge and practice before and after intervention. RESULTS Initially, a majority of the sample (76%) reported poor levels of foot care. After 12 weeks <1% reported poor foot care practices. Statistical testing showed significant gains in knowledge (by score and level) and nearly unanimous compliance with daily foot examination. CONCLUSION Mobile phone text messaging is an economical, feasible, and effective method for educators to improve diabetic self-care, even in a developing country.
Study of thermal cycle, mechanical, and metallurgical properties of friction stir welded aviation grade aluminum alloy

This research work presents the study of thermal cycle during friction stir welding of aviation grade aluminum alloy. In addition, mechanical and metallurgical properties of friction stir welded joints are conceptually discussed. Experimentation has been conducted in two stages. Stage I experiments has been conducted as per one-factor-at-a-time approach with varying tilt angle and dwell time. It was concluded that maximum ultimate tensile strength is obtained at 2° tilt angle and 30 s dwell time by one-factor-at-a-time approach. On the basis of stage I results, full-factorial design is used for conducting main experiments by fixing the tilt angle and dwell time. Stage II has been attempted to optimize the most influencing friction stir welding parameters: rotational speed and traverse speed. It is observed that rotational speed is predominant factors for ultimate tensile strength and traverse speed for microhardness. In addition, eight thermocouples (L-shaped k type), four on the advancing side and four on the retreating side, are placed at equal distance from the centerline for measuring the temperature during the process. The optical microscope and energy beam scattered diffraction analysis have been carried out for scrutinizing the macrostructure and microstructure of friction stir welded joints. It is evident from energy beam scattered diffraction analysis that the grain size of nugget zone decreases as compared to base metal.
Carbon nanotubes filled with continuous ferromagnetic α-Fe nanowires and surface-functionalized with paramagnetic Gd(III) : a candidate magnetic hyperthermia structure and MRI contrast agent

The main goal of this project was the development of carbon nanotubes as a candidate for dual-functioning magnetic hyperthermia structure and magnetic resonance imaging contrast agent. This was achieved by filling carbon nanotubes with continuous ferromagnetic α-Fe nanowires and surface functionalized with paramagnetic Gd(III). Also, length control of both nanotube and nanowire was investigated. Firstly, a low vapour flow-rate and constant evaporation temperature chemical vapour deposition method based on the thermal decomposition of ferrocene was employed which achieved continuous α-Fe nanowires on the same scale as the nanotube for lengths >10 μm without the necessity of post-synthesis heat-treatment or introduction of other precursor elements. The low vapour flow-rate regime has the advantage of sustaining the intrinsic temperature gradient at the tip of the forming structure which drives the vapour feedstock to the growth front to guarantee continuous nanowire formation. For initially mixed-phase nanowires of length less than 10 μm, the continuous α-Fe nanowires were achieved by postsynthesis heat treatment. Secondly, a simple wet chemical method involving only sonication in aqueous GdCl3 solution was used for surface functionalization of iron-filled multiwalled carbon nanotubes with gadolinium. Functional groups on the sidewalls produced by the sonication provide active nucleation sites for the loading of Gd
Adult Survivors of Childhood Cancer Have Poor Adherence to Dietary Guidelines.

BACKGROUND Poor nutritional intake can exacerbate the chronic disease burden in childhood cancer survivors, whereas a healthful diet serves a protective function. Few studies have provided detailed evaluations of the diet of childhood cancer survivors. OBJECTIVES This study aimed to evaluate diet quality and dietary intakes of key food groups and nutrients in a large cohort of childhood cancer survivors and whether cancer and treatment characteristics have an impact on survivors' long-term intake. METHODS Diet was assessed in 2570 adult survivors of childhood cancer enrolled in the St. Jude Lifetime cohort (mean age = 32.3 y) by using the Block food-frequency questionnaire. The Healthy Eating Index-2010 (HEI-2010) was calculated to quantify diet quality. Cancer diagnosis and treatment exposure were abstracted from medical records. Differences in HEI-2010 by patient characteristics and treatment exposure were examined by using ANCOVA. RESULTS The mean ± SD HEI-2010 in childhood cancer survivors was 57.9 ± 12.4 of a maximum score of 100. Referenced to Dietary Reference Intakes, survivors consumed inadequate amounts of vitamin D, vitamin E, potassium, fiber, magnesium, and calcium (27%, 54%, 58%, 59%, 84%, and 90% of the recommended intakes) but excessive amounts of sodium and saturated fat (155% and 115% of the recommended intakes) from foods. Survivors diagnosed when <5 y of age had a lower diet quality than did those diagnosed when ≥5 y of age (mean HEI-2010 score: 56.9 compared with 58.2; P = 0.046). Survivors who received higher radiation doses to the abdomen had a lower diet quality than those who received lower doses (mean HEI-2010 scores = 58.9, 57.2, 56.7, and 56.1 for doses of 0, 1-19.9, 20-29.9, and ≥30 Gy, respectively; P = 0.02). CONCLUSIONS Long-term childhood cancer survivors have poor adherence to the 2010 Dietary Guidelines for Americans. Findings reinforce the need to incorporate nutrition into cancer care to improve diet quality and to reduce morbidities.
Whole-Body Vibration Improves Early Rate of Torque Development in Individuals With Anterior Cruciate Ligament Reconstruction

Abstract Pamukoff, DN, Pietrosimone, B, Ryan, ED, Lee, DR, Brown, LE, and Blackburn, JT. Whole body vibration improves early rate of torque development in individuals with anterior cruciate ligament reconstruction. J Strength Cond Res 31(11): 2992–3000, 2017—The purpose of this study was to compare the effect of whole-body vibration (WBV) and local muscle vibration (LMV) on early and late quadriceps rate of torque development (RTD), and electromechanical delay (EMD) in individuals with anterior cruciate ligament reconstruction (ACLR). Twenty individuals with ACLR were recruited for this study. Participants performed isometric squats while being exposed to WBV, LMV, or no vibration (control) in a randomized order during separate visits. Early and late quadriceps RTD and EMD were assessed during a maximal voluntary isometric knee extension before and immediately after WBV, LMV, or control. There was a significant condition by time interaction for early RTD (p = 0.045) but not for late RTD (p = 0.11) or EMD of the vastus medialis (p = 0.15), vastus lateralis (p = 0.17), or rectus femoris (p = 0.39). Post hoc analyses indicated a significant increase in early RTD after WBV (+5.59 N·m·s−1·kg−1; 95% confidence interval, 1.47–12.72; p = 0.007). No differences were observed in the LMV or control conditions, and no difference was observed between conditions at posttest. The ability to rapidly produce knee extension torque is essential to physical function, and WBV may be appropriate to aid in the restoration of RTD after ACLR.
All-Pedicle Screw Fixation With 6-mm-Diameter Cobalt-Chromium Rods Provides Optimized Sagittal Correction of Adolescent Idiopathic Scoliosis

Purpose: Recently introduced cobalt-chromium (CoCr) rods that rely solely on pedicle screws produce very good results in correcting scoliotic curves. All-pedicle screws constructs are also suspected of decreasing thoracic kyphosis. The current study was designed to evaluate sagittal correction in adolescent idiopathic scoliosis patients, using 6-mm CoCr rods and all-screw constructs. Materials and Methods: A total of 61 patients treated by posterior spinal fusion and instrumentation, using all-pedicle screw constructs were included. The mean age at surgery was 15.4 years (range, 12–18 y). Forty-five patients (group A) were diagnosed with decreased thoracic kyphosis, and 16 patients (group B) had normal (35–50 degrees) thoracic kyphosis. Results: The preoperative main Cobb angle was 62.93±19.38 degrees in group A and 73.45±22.13 degrees in group B. In group A, the postoperative main Cobb angle was 23.33±12.71 degrees. In group B, the postoperative main Cobb angle was 27.20±10.04 degrees. The T4–T12 thoracic kyphosis improved postoperatively from 18.15±10.29 to 28.18±8.35 degrees in group A. In group B, the postoperative T4–T12 thoracic kyphosis was 40.34±3.13 degrees. Statistical analysis showed a significant improvement between preoperative and postoperative values of T4–T12 thoracic kyphosis in group A. In group B, the differences in T4–T12 thoracic kyphosis values were not statistically significant. Conclusions: Our result demonstrates a significant improvement of T4–T12 thoracic kyphosis in the hypokyphotic group of patients and confirms that CoCr rods can produce sagittal corrections in hypokyphotic adolescent idiopathic scoliosis patients. Our results confirm the benefit of combining all-pedicle screw constructs with a posterolateral translational in situ bending procedure to correct hypokyphosis directly.
Design and Applications of a Pen-Like Haptic Interface with Texture and Vibrotactile Display

This paper presents a pen-like haptic interface with a built-in compact tactile display module and a vibrating module. We describe evaluations verifying its performance and indicating that it can satisfactorily represent tactile patterns and provide vibrotactile feedback. Its applicability to combined force and tactile feedback display in a pen held haptic device is also investigated. Finally, we evaluate its capacity to support touch screen operations by providing tactile sensations when a user rubs against an image displayed on a monitor.
Parainfluenza Virus Infection Sensitizes Cancer Cells to DNA-Damaging Agents: Implications for Oncolytic Virus Therapy

ABSTRACT A parainfluenza virus 5 (PIV5) with mutations in the P/V gene (P/V-CPI−) is restricted for spread in normal cells but not in cancer cells in vitro and is effective at reducing tumor burdens in mouse model systems. Here we show that P/V-CPI− infection of HEp-2 human laryngeal cancer cells results in the majority of the cells dying, but unexpectedly, over time, there is an emergence of a population of cells that survive as P/V-CPI− persistently infected (PI) cells. P/V-CPI− PI cells had elevated levels of basal caspase activation, and viability was highly dependent on the activity of cellular inhibitor-of-apoptosis proteins (IAPs) such as Survivin and XIAP. In challenge experiments with external inducers of apoptosis, PI cells were more sensitive to cisplatin-induced DNA damage and cell death. This increased cisplatin sensitivity correlated with defects in DNA damage signaling pathways such as phosphorylation of Chk1 and translocation of damage-specific DNA binding protein 1 (DDB1) to the nucleus. Cisplatin-induced killing of PI cells was sensitive to the inhibition of wild-type (WT) p53-inducible protein 1 (WIP1), a phosphatase which acts to terminate DNA damage signaling pathways. A similar sensitivity to cisplatin was seen with cells during acute infection with P/V-CPI− as well as during acute infections with WT PIV5 and the related virus human parainfluenza virus type 2 (hPIV2). Our results have general implications for the design of safer paramyxovirus-based vectors that cannot establish PI as well as the potential for combining chemotherapy with oncolytic RNA virus vectors. IMPORTANCE There is intense interest in developing oncolytic viral vectors with increased potency against cancer cells, particularly those cancer cells that have gained resistance to chemotherapies. We have found that infection with cytoplasmically replicating parainfluenza virus can result in increases in the killing of cancer cells by agents that induce DNA damage, and this is linked to alterations to DNA damage signaling pathways that balance cell survival versus death. Our results have general implications for the design of safer paramyxovirus-based vectors that cannot establish persistent infection, the repurposing of drugs that target cellular IAPs as antivirals, and the combined use of DNA-damaging chemotherapy agents in conjunction with oncolytic RNA virus vectors.
Fine Motor Skill Mediates Visual Memory Ability with Microstructural Neuro-correlates in Cerebellar Peduncles in Prematurely Born Adolescents

Abstract Adolescents born preterm (PT) with no evidence of neonatal brain injury are at risk of deficits in visual memory and fine motor skills that diminish academic performance. The association between these deficits and white matter microstructure is relatively unexplored. We studied 190 PTs with no brain injury and 92 term controls at age 16 years. The Rey‐Osterrieth Complex Figure Test (ROCF), the Beery visual‐motor integration (VMI), and the Grooved Pegboard Test (GPT) were collected for all participants, while a subset (40 PTs and 40 terms) underwent diffusion‐weighted magnetic resonance imaging. PTs performed more poorly than terms on ROCF, VMI, and GPT (all P < 0.01). Mediation analysis showed fine motor skill (GPT score) significantly mediates group difference in ROCF and VMI (all P < 0.001). PTs showed a negative correlation (P < 0.05, corrected) between fractional anisotropy (FA) in the bilateral middle cerebellar peduncles and GPT score, with higher FA correlating to lower (faster task completion) GPT scores, and between FA in the right superior cerebellar peduncle and ROCF scores. PTs also had a positive correlation (P < 0.05, corrected) between VMI and left middle cerebellar peduncle FA. Novel strategies to target fine motor skills and the cerebellum may help PTs reach their full academic potential.
Ongoing Alpha Activity in V1 Regulates Visually Driven Spiking Responses

Abstract The interlaminar connections in the primate primary visual cortex (V1) are well described, as is the presence of ongoing alpha‐range (7‐14 Hz) fluctuations in this area. Less well understood is how these interlaminar connections and ongoing fluctuations contribute to the regulation of visual spiking responses. Here, we investigate the relationship between alpha fluctuations and spiking responses to visual stimuli across cortical layers. Using laminar probes in macaque V1, we show that neural firing couples with the phase of alpha fluctuations, and that magnitude of this coupling is particularly pronounced during visual stimulation. The strongest modulation of spiking activity was observed in layers 2/3. Alpha‐spike coupling and current source density analysis pointed to an infragranular origin of the alpha fluctuations. Taken together, these results indicate that ongoing infragranular alpha‐range fluctuations in V1 play a role in regulating columnar visual activity.