Miracle-dz/UniFAR-FTUs huggingface dataset:
Prognostic significance of USP33 in advanced colorectal cancer patients: new insights into β-arrestin-dependent ERK signaling

Patients with liver metastases of colorectal cancer (CRCLM) have a poorer prognosis compared to colorectal cancer (CRC) patients in local stage. Evaluating the recurrence and overall survival of advanced patients is critical in improving disease treatment and clinical outcome. Here we investigated the expression pattern of USP33, a deubiquitinating enzyme, in both primary CRC tissues and liver metastases tissues. Univariate and multivariate analyses identified that low expression of USP33 in CRCLM tissues indicated high recurrence risk and poor overall prognosis. Overexpression of USP33 can significantly inhibit cell proliferation, migration, and invasion. On the other hand, USP33 knock-down promoted cell proliferation and invasion under SDF-1 stimulation; whereas dynasore (an internalization inhibitor) pretreatment in USP33 silencing cells showed a distinct antipromoting effect, revealing the participation of CXCR4 internalization in regulating tumor progress. Further results verified that USP33 can deubiquitinate β-arrestin2, subsequently block the internalization of SDF-1-stimulated CXCR4, and disrupt β-arrestin-dependent ERK activation. The existence and functions of β-arrestin-dependent signaling have been previously determined in several Gs-coupled receptors, such as β2-adrenergic receptor and angiotensin receptor subtype 1a; however, little is known about this in Gi-coupled receptors. Our study not only established USP33 as a novel prognosis biomarker in advanced CRCLM patients, but also highlighted the significance of β-arrestin-dependent ERK signaling in cancer development.
Does insurance enrolment increase healthcare utilisation among rural-dwelling older adults? Evidence from the National Health Insurance Scheme in Ghana

Introduction This paper examines the relationship between national health insurance enrolment and the utilisation of inpatient and outpatient healthcare for older adults in rural areas in Ghana. The Ghanaian National Health Insurance Scheme (NHIS) aims to improve affordability and increase the utilisation of healthcare. However, the system has been criticised for not being responsive to the needs of older adults. The majority of older adults in Ghana live in rural areas with poor accessibility to healthcare. With an ageing population, a specific assessment of whether the scheme has benefitted older adults, and also if the benefit is equitable, is needed. Methods Using the Ghanaian Living Standards Survey from 2012 to 2013, this paper uses propensity score matching to estimate the effect of enrolment within the NHIS on the utilisation of inpatient and outpatient care among older people aged 50 and over. Results The raw results show higher utilisation of healthcare among NHIS members, which persists after matching. NHIS members were 6% and 9% more likely to use inpatient and outpatient care, respectively, than non-members. When these increases were disaggregated for outpatient care, the non-poor and females were seen to benefit more than their poor and male counterparts. For inpatient care, the benefits of enrolment were equal by poverty status and sex. However, overall, poor older adults use health services much less than the non-poor older adults even when enrolled. Conclusion The results indicate that NHIS coverage does increase healthcare utilisation among rural older adults but that inequalities remain. The poor are still at a great disadvantage in their use of health services overall and benefit less from enrolment for outpatient care. The receipt of healthcare is significantly influenced by a set of auxiliary barriers to access to healthcare even where insurance should remove the financial burden of ad hoc out of pocket payments.
Epigenetic Control of the Vasopressin Promoter Explains Physiological Ability to Regulate Vasopressin Transcription in Dehydration and Salt Loading States in the Rat

The synthesis of arginine vasopressin (AVP) in the supraoptic nucleus (SON) and paraventricular nucleus (PVN) of the hypothalamus is sensitive to increased plasma osmolality and a decreased blood volume, and thus is robustly increased by both dehydration (increased plasma osmolality and decreased blood volume) and salt loading (increased plasma osmolality). Both stimuli result in functional remodelling of the SON and PVN, a process referred to as functional‐related plasticity. Such plastic changes in the brain have recently been associated with altered patterns of DNA methylation at CpG (cytosine‐phosphate‐guanine) residues, a process considered to be important for the regulation of gene transcription. In this regard, the proximal Avp promoter contains a number of CpG sites and is recognised as one of four CpG islands for the Avp gene, suggesting that methylation may be regulating Avp transcription. In the present study, we show that, in an immortalised hypothalamic cell line 4B, the proximal Avp promoter is highly methylated, and treatment of these cells with the DNA methyltransferase inhibitor 5‐Aza‐2′‐deoxycytidine to demethylate DNA dramatically increases basal and stimulated Avp biosynthesis. We report no changes in the expression of DNA methyltransferases, Dnmt1 and Dnmt3a, whereas there is decreased expression of the demethylating enzyme ten‐eleven‐translocation 2, Tet2, in the SON by dehydration and salt loading. We found higher methylation of the SON Avp promoter in dehydrated but not salt‐loaded rats. By analysis of individual CpG sites, we observed hypomethylation, hypermethylation and no change in methylation of specific CpGs in the SON Avp promoter of the dehydrated rat. Using reporter gene assays, we show that mutation of individual CpGs can result in altered Avp promoter activity. We propose that methylation of the SON Avp promoter is necessary to co‐ordinate the duel inputs of increased plasma osmolality and decreased blood volume on Avp transcription in the chronically dehydrated rat.
Distinguish Dynamic Basic Blocks by Structural Statistical Testing

Statistical testing aims at generating random test data that respect selected probabilistic properties. A distribution probability is associated with the program input space in order to achieve statistical test purpose: to test the most frequent usage of software or to maximize the probability of satisfying a structural coverage criterion for instance. In this paper, we propose a new statistical testing method that generates sequences of random test data that respect the following probabilistic properties: 1) each sequence guarantees the uniform selection of feasible paths only and 2) the uniform selection of test data over the subdomain associated with these paths. Baudry et al. present a testing-for-diagnosis method where the essential notion of Dynamic Basic Block was identified to be strongly correlated to the effectiveness of fault-localization technique. We show that generating a sequence of random test data respecting these properties allows to well-distinguished Dynamic Basic Blocks. Thanks to Constraint programming techniques, we propose an efficient algorithm that uniformly selects feasible paths only by drastically decreasing the number of rejects (test data that activate another control flow path) during the test data selection. We implemented this algorithm in a statistical test data generator for Java programs. A first experimental validation is presented.
Sex Differences in Physician Salary in US Public Medical Schools.

IMPORTANCE Limited evidence exists on salary differences between male and female academic physicians, largely owing to difficulty obtaining data on salary and factors influencing salary. Existing studies have been limited by reliance on survey-based approaches to measuring sex differences in earnings, lack of contemporary data, small sample sizes, or limited geographic representation. OBJECTIVE To analyze sex differences in earnings among US academic physicians. DESIGN, SETTING, AND PARTICIPANTS Freedom of Information laws mandate release of salary information of public university employees in several states. In 12 states with salary information published online, salary data were extracted on 10 241 academic physicians at 24 public medical schools. These data were linked to a unique physician database with detailed information on sex, age, years of experience, faculty rank, specialty, scientific authorship, National Institutes of Health funding, clinical trial participation, and Medicare reimbursements (proxy for clinical revenue). Sex differences in salary were estimated after adjusting for these factors. EXPOSURES Physician sex. MAIN OUTCOMES AND MEASURES Annual salary. RESULTS Among 10 241 physicians, female physicians (n = 3549) had lower mean (SD) unadjusted salaries than male physicians ($206 641 [$88 238] vs $257 957 [$137 202]; absolute difference, $51 315 [95% CI, $46 330-$56 301]). Sex differences persisted after multivariable adjustment ($227 783 [95% CI, $224 117-$231 448] vs $247 661 [95% CI, $245 065-$250 258] with an absolute difference of $19 878 [95% CI, $15 261-$24 495]). Sex differences in salary varied across specialties, institutions, and faculty ranks. For example, adjusted salaries of female full professors ($250 971 [95% CI, $242 307-$259 635]) were comparable to those of male associate professors ($247 212 [95% CI, $241 850-$252 575]). Among specialties, adjusted salaries were highest in orthopedic surgery ($358 093 [95% CI, $344 354-$371 831]), surgical subspecialties ($318 760 [95% CI, $311 030-$326 491]), and general surgery ($302 666 [95% CI, $294 060-$311 272]) and lowest in infectious disease, family medicine, and neurology (mean income, <$200 000). Years of experience, total publications, clinical trial participation, and Medicare payments were positively associated with salary. CONCLUSIONS AND RELEVANCE Among physicians with faculty appointments at 24 US public medical schools, significant sex differences in salary exist even after accounting for age, experience, specialty, faculty rank, and measures of research productivity and clinical revenue.
Subconjuctival Loa loa with Calabar Swelling

Loa loa is unique among the human filariae in that adult worms are occasionally visible during subconjuntival migration. A 29-yr-old African female student, living in Korea for the past 5 yr without ever visiting her home country, presented with acute eyelid swelling and a sensation of motion on the left eyeball. Her symptoms started one day earlier and became worse over time. Examination revealed a threadlike worm beneath the left upper bulbar conjunctiva with mild eyelid swelling as well as painless swelling of the right forearm. Upon exposure to slit-lamp illumination, a sudden movement of the worm toward the fornix was noted. After surgical extraction, parasitologic analysis confirmed the worm to be a female adult Loa loa with the vulva at the extreme anterior end. On blood smear, the microfilariae had characteristic features of Loa loa, including sheath and body nuclei up to the tip of the tail. The patient also showed eosinophilia (37%) measuring 4,100/µL. She took ivermectin (200 µg/kg) as a single dose and suffered from a mild fever and chills for one day. This patient, to the best of our knowledge, is the first case of subconjunctival loiasis with Calabar swelling in Korea.
Vitamin D–Binding Protein Enhances Epithelial Ovarian Cancer Progression by Regulating the Insulin-like Growth Factor-1/Akt Pathway and Vitamin D Receptor Transcription

Purpose: Malignant ascites of epithelial ovarian cancer (EOC) helps identify prognostic biomarkers or mechanisms of tumor progression. Vitamin D–binding protein (DBP) was revealed to be upregulated in EOC ascites in our previous proteomic study. Here, we examined the role of DBP in EOC. Experimental Design: We analyzed ascites, serum, and tissue samples of patients with newly diagnosed EOC to determine the prognostic effects of DBP. We verified DBP function using orthotopic animal models and DBP regulation in ovarian cancer cell lines. Results: Elevated ascitic DBP was significantly associated with poor response to chemotherapy, short progression-free interval, increased cancer progression, and death. Ascitic DBP overexpression was an independent unfavorable biomarker for progression-free survival; DBP overexpression in cancerous tissue was significantly related to chemoresistance. In vivo and in vitro investigations demonstrated an important role for DBP in ovarian cancer progression. Orthotopic model mice inoculated with DBP knockdown ovarian cancer cells displayed a significant reduction in tumor formation, malignant cell number, ascitic DBP levels, invasiveness, and metastasis, and increased survival compared with controls. In presence of vitamin D receptor (VDR), DBP promoted cell aggression (invasion and doubling time) via activation of the insulin-like growth factor-1/insulin-like growth factor–binding protein-2/Akt axis, and induced suppression of vitamin D–responsive genes. A NF-κB p65-binding site in the VDR promoter was identified as a major determinant of DBP-dependent VDR promoter activation. Conclusions: This study highlights the importance of DBP in ovarian tumor progression and the potential application of DBP as a therapeutic target for EOC. Clin Cancer Res; 24(13); 3217–28. ©2018 AACR.
Active disturbance rejection for walking bipedal robots using the acceleration of the upper limbs

SUMMARY A disturbance rejection controller is proposed based on the general dynamic model of 3D biped robots. For the first time, with this proposed approach, not only the Zero Moment Point (ZMP) location remains unchanged in presence of disturbances but also the longitudinal and lateral ground reaction forces and the vertical twist moment remain unchanged. This way, slipping as well as tipping is prevented by the controller. The swing phase of the robot's walking gait is considered. An integral sliding mode architecture is chosen for the disturbance rejection. The support forces and moments of the stance foot are the control outputs. The acceleration of the arm/body joints are chosen as the inputs. During the disturbance rejection, the leg joints remain at their desired trajectory. Since the leg joint trajectories are unaffected, the robot is still able to complete its step as planned, even when bounded disturbances are experienced. For simulations, the general method is applied to an 18-degree of freedom biped humanoid robot. Simulations show that the controller successfully mitigates bounded disturbances and maintains all of the support reactions extremely close to their desired values. Consequently, the shift in the position of the ZMP is negligible, and the robot foot does not slip.
A soft-commutation Space Vector Modulation (SVM) for current source converter with full-range power factor

A current soft-commutation Space Vector Modulation (SVM) scheme for three-phase current source converter (CSC) is proposed in this paper. With the presented SVM, the incoming switch has a positive collector-to-emitter voltage while the outgoing switch has a negative collector-to-emitter voltage during current commutations. That is, natural soft-commutations for switching transitions are achieved with accelerated current-commutating processes and lessened durations. As a result, distortion of the line currents can be reduced. Besides, due to the lessened overlapping time, the switching frequency is expected to reach as high as possible to reduce the ac filter and improve the line current quality. Especially, since the presented SVM is based on a closed-loop strategy, soft commutations can be reached in CSC with any power factor operation. The experiment verifies the proposition.
Accelerating Multiplication and Parallelizing Operations in Non-Volatile Memory

Today’s IoT applications often analyze raw data by running machine learning algorithms such as classification or neural networks in data centers [2], [3]. Sending the entire data to cloud for processing is not scalable and cannot guarantee the required realtime response [4]. Running data intensive workloads with large datasets on traditional cores results in high energy consumption and slow processing speed, majorly due to the large amount of data movement between memory and processing units [5], [6]. The idea of processing in-memory aims to reduce this problem by avoiding the memory/cache bottleneck. It reduces data movement by processing data within the memory, thus improving both performance and energy efficiency [7], [6]. On the other hand, most of the algorithms running on today’s sensors’ data are statistical in nature, and thus do not require exact answers [8], [9]. Similarly, in audio and video processing we have long exploited the fact that humans do not perceive all the colors or sounds equally well. Approximate computing is an effective way of improving the energy and performance by trading some accuracy. However, most of the existing techniques provide less energy or performance efficiency due to considerable data movement and lack of configurable accuracy. In this paper, we propose a configurable approximate processing in-memory architecture, called APIM, which supports addition and multiplication operations inside the non-volatile RRAM-based memory. APIM exploits the analog characteristic of the memristor devices to enable basic bitwise computation and then, extend it to fast and configurable addition and multiplication within memory. This would make processing machine learning and data analysis algorithms more efficient since most of them use addition and multiplication aggressively. We propose a blocked crossbar memory which, along with the configurable interconnects, introduces flexibility in executing operations and facilitates shift operations in memory. Then, we introduce a novel approach for fast addition in memory. Finally, we design an in-memory multiplier using the proposed memory unit and fast adder. For each application, APIM can dynamically tune the level of approximation in order to trade the accuracy of computation while improving energy and performance. Our experimental evaluation over six general OpenCL applications shows that the proposed design improves the performance by 20× and provides 480× improvement in energydelay product while ensuring less than 10% average relative error.
Does large-scale ocean circulation structure life history connectivity in Antarctic toothfish (Dissostichus mawsoni)?

A multidisciplinary approach incorporating otolith chemistry, age data, and numerical Lagrangian particle simulations indicated a single, self-recruiting population of Antarctic toothfish (Dissostichus mawsoni) in the Southeast Pacific Basin (SPB) and Ross Sea, with a life history structured by the large-scale circulation. Chemistry deposited prior to capture along otolith edges demonstrated strong environmental heterogeneity, yet the chemistry in otolith nuclei, deposited during early life, showed no differences. Age data showed only adult fish in catches on the Pacific–Antarctic Ridge in the SPB and structuring of life stages consistent with transport pathways from the northern Ross Sea. Lagrangian particle simulations predicted that early life stages following the flow in the SPB would be transported to areas in the Ross Sea where juveniles are caught, whereas the circulation would facilitate adult movement along the shelf slope and back into the SPB where spawning adults are caught. These results sugg.
Effects of a Pain Catastrophizing Induction on Sensory Testing in Women with Chronic Low Back Pain: A Pilot Study

Pain catastrophizing, a pattern of negative cognitive-emotional responses to actual or anticipated pain, maintains chronic pain and undermines response to treatments. Currently, precisely how pain catastrophizing influences pain processing is not well understood. In experimental settings, pain catastrophizing has been associated with amplified pain processing. This study sought to clarify pain processing mechanisms via experimental induction of pain catastrophizing. Forty women with chronic low back pain were assigned in blocks to an experimental condition, either a psychologist-led 10-minute pain catastrophizing induction or a control (10-minute rest period). All participants underwent a baseline round of several quantitative sensory testing (QST) tasks, followed by the pain catastrophizing induction or the rest period, and then a second round of the same QST tasks. The catastrophizing induction appeared to increase state pain catastrophizing levels. Changes in QST pain were detected for two of the QST tasks administered, weighted pin pain and mechanical allodynia. Although there is a need to replicate our preliminary results with a larger sample, study findings suggest a potential relationship between induced pain catastrophizing and central sensitization of pain. Clarification of the mechanisms through which catastrophizing affects pain modulatory systems may yield useful clinical insights into the treatment of chronic pain.
An omics perspective to the molecular mechanisms of anticancer metallo-drugs in the computational microscope era

ABSTRACT Introduction: Metallo-drugs have attracted enormous interest for cancer treatment. The achievements of this drug-type are summarized by the success story of cisplatin. That being said, there have been many drawbacks with its clinical use, which prompted decades worth of research efforts to move towards safer and more effective agents, either containing platinum or different metals. Areas covered: In this review, the authors provide an atomistic picture of the molecular mechanisms involving selected metallo-drugs from structural and molecular simulation studies. They also provide an omics perspective, pointing out many unsettled aspects of the most relevant families of metallo-drugs at an epigenetic level. Expert opinion: Molecular simulations are able to provide detailed information at atomistic and temporal (ps) resolutions that are rarely accessible to experiments. The increasing accuracy of computational methods and the growing performance of computational platforms, allow us to mirror wet lab experiments in silico. Consequently, the molecular mechanisms of drugs action/failure can be directly viewed on a computer screen, like a ‘computational microscope’, allowing us to harness this knowledge for the design of the next-generation of metallo-drugs.
An ultrasonic-based localization system for underground mines

Localization is important for a wide range of industries and applications. In underground mining, for instance, it is helpful to know the miners' locations, particularly in emergency situations. One way this can be achieved is by using ultrasonic based localization. This paper presents the design and implementation of a wireless sensor network which can be deployed in underground mines to perform time-difference-of-arrival based localization. It is shown that the implemented ultrasound receivers are resistant to noisy conditions that may arise in harsh underground environments.