Miracle-dz/UniFAR-FTUs huggingface dataset:
HGF/MET pathway aberrations as diagnostic, prognostic, and predictive biomarkers in human cancers

Abstract Cancer is a major cause of death worldwide. MET tyrosine kinase receptor [MET, c-MET, hepatocyte growth factor (HGF) receptor] pathway activation is associated with the appearance of several hallmarks of cancer. The HGF/MET pathway has emerged as an important actionable target across many solid tumors; therefore, biomarker discovery becomes essential in order to guide clinical intervention and patient stratification with the aim of moving towards personalized medicine. The focus of this review is on how the aberrant activation of the HGF/MET pathway in tumor tissue or the circulation can provide diagnostic and prognostic biomarkers and predictive biomarkers of drug response. Many meta-analyses have shown that aberrant activation of the MET pathway in tumor tissue, including MET gene overexpression, gene amplification, exon 14 skipping and other activating mutations, is almost invariably associated with shorter survival and poor prognosis. Most meta-analyses have been performed in non-small cell lung cancer (NSCLC), breast, head and neck cancers as well as colorectal, gastric, pancreatic and other gastrointestinal cancers. Furthermore, several studies have shown the predictive value of MET biomarkers in the identification of patients who gain the most benefit from HGF/MET targeted therapies administered as single or combination therapies. The highest predictive values have been observed for response to foretinib and savolitinib in renal cancer, as well as tivantinib in NSCLC and colorectal cancer. However, some studies, especially those based on MET expression, have failed to show much value in these stratifications. This may be rooted in lack of standardization of methodologies, in particular in scoring systems applied in immunohistochemistry determinations or absence of oncogenic addiction of cancer cells to the MET pathway, despite detection of overexpression. Measurements of amplification and mutation aberrations are less likely to suffer from these pitfalls. Increased levels of MET soluble ectodomain (sMET) in circulation have also been associated with poor prognosis; however, the evidence is not as strong as it is with tissue-based biomarkers. As a diagnostic biomarker, sMET has shown its value in distinguishing cancer patients from healthy individuals in prostate and bladder cancers and in melanoma. On the other hand, increased circulating HGF has also been presented as a valuable prognostic and diagnostic biomarker in many cancers; however, there is controversy on the predictive value of HGF as a biomarker. Other biomarkers such as circulating tumor DNA (ctDNA) and tumor HGF levels have also been briefly covered. In conclusion, HGF/MET aberrations can provide valuable diagnostic, prognostic and predictive biomarkers and represent vital assets for personalized cancer therapy.
The Impact of Formal Social Support on Outpatient Care Among a Sample of Adults Living with HIV/AIDS in the United States

Title of Document: THE IMPACT OF FORMAL SOCIAL SUPPORT ON OUTPATIENT CARE AMONG A SAMPLE OF ADULTS LIVING WITH HIV/AIDS IN THE UNITED STATES Sabrina A. Matoff-Stepp, Ph.D., 2007 Directed By: Professor Bradley O. Boekeloo, Department of Public and Community Health Background The HIV Cost and Services Utilization Study and HIV Research Network (HIVRN) clinical studies showed disparities among HIV-positive men and women in outpatient care use in the U.S. Formal social support provided by case managers may help patients access outpatient care. The primary purpose of this study was to determine if having case managers is associated with levels of outpatient care visits among 797 individuals living with HIV/AIDS, and whether this association varies by patient sex. Other aims were to determine if the number of in-person case management visits and the type of formal social support are associated with these same outcomes. Outpatient visit levels were defined as 2-5 (average) or 6+ (high). Based on Andersen’s (1995) Behavioral Model of Health Services Use, a conceptual model was developed as a framework for examining the study’s hypothesized relationships. Methods The HIVRN is a convenience sample of 17 U.S. clinical sites serving more than 15,000 people living with HIV/AIDS. In 2003, interviews were conducted with a stratified sample of 951 clients at 14 HIVRN sites. The current study sample consisted of 797 adult respondents (543 males and 254 females). Logistic regression was used to identify significant predictors of outpatient care visit levels. Results Patients who had one or two case managers versus no case managers were significantly more likely to have 6+ outpatient visits, while patients who were employed and had higher self-reported perceptions of their health were significantly less likely to have 6+ outpatient visits. These relationships did not vary by patient sex. Level of outpatient visits also did not vary by patient sex. No significant associations were found between the number of in-person case management visits or the type of formal social support and level of outpatient visits. In sub-analyses that separated patients with one case manager from those with two case managers, no new predictors emerged. Conclusion Case management was associated with higher levels of outpatient visits for both male and female patients in this study. This finding suggests that utilization of HIV-related outpatient care may be increased among both men and women with case management. THE IMPACT OF FORMAL SOCIAL SUPPORT ON OUTPATIENT CARE AMONG A SAMPLE OF ADULTS LIVING WITH HIV/AIDS IN THE UNITED STATES
The role of study material in the Professional development of Physics Teachers in Distance Education

Research has been done for the past 4 years with 75 Physical Science teachers to construct and test a holistic model for professional development via Distance Education. Three dimensions were targeted that need development, namely, the teachers’ physics content knowledge, their teaching approaches and professional attitudes. In the first phase of the research, baseline data were obtained to see if there is a problem in these dimensions. In the second and third phase a model was developed and trialled each time with a new set of teachers in the urban and rural parts of South Africa. In the fourth phase an analysis of the model was done. Evidence shows that the teachers changed from being caught in a vicious circle of poor content knowledge, lack of confidence and enjoyment and unwillingness to spend time on task (poor professional attitudes, ineffective teaching approaches) to being part of a virtuous circle of improved content knowledge, more confidence and enjoyment and willingness to spend more time on task (better professional attitudes and effective teaching approaches).
Imaging endogenous synaptic proteins in primary neurons at single-cell resolution using CRISPR/Cas9

Fluorescence imaging at single-cell resolution is a crucial approach to analyzing the spatiotemporal regulation of proteins within individual cells of complex neural networks. Here we present a nonviral strategy that enables the tagging of endogenous loci by CRISPR/Cas9-mediated genome editing combined with a nucleofection technique. The method allowed expression of fluorescently tagged proteins at endogenous levels, and we successfully achieved tagging of a presynaptic protein, synaptophysin (Syp), and a postsynaptic protein, PSD-95, in cultured postmitotic neurons. Superresolution fluorescence microscopy of fixed neurons confirmed the identical localization patterns of the tagged proteins to those of endogenous ones verified by immunohistochemistry. The system is also applicable for multiplexed labeling and live-cell imaging. Live imaging with total internal reflection fluorescence microscopy of a single dendritic process of a neuron double-labeled with Syp-mCherry and PSD-95-EGFP revealed the previously undescribed dynamic localization of the proteins synchronously moving along dendritic shafts. Our convenient and versatile strategy is potent for analysis of proteins whose ectopic expressions perturb cellular functions.
A Novel Anti-Cd40 Monoclonal Antibody, Iscalimab, for Control of Graves' Hyperthyroidism - A Proof-Of-Concept Trial.

CONTEXT The CD40-CD154 co-stimulatory pathway plays an important role in the pathogenesis of Graves' disease (GD) by promoting auto-reactive B cell activation. OBJECTIVE Evaluate efficacy and safety of a human, blocking, non-depleting anti-CD40 monoclonal antibody, iscalimab, in hyperthyroid patients with GD. DESIGN Open label, phase II proof-of-concept study. SETTING Multicenter. PATIENTS Fifteen with GD. INTERVENTION Patients received five doses of iscalimab at 10 mg/kg intravenously over 12 weeks. MAIN OUTCOME MEASURES Thyroid-related hormones and autoantibodies, plasma soluble CD40, free CD40 on B cells, soluble CXCL13, pharmacokinetics, and safety were assessed. RESULTS The iscalimab intervention resulted in complete CD40 engagement for up to 20 weeks. A clinical response and biochemical euthyroidism was observed in seven of 15 (47%) patients. Free and total T3 and T4 normalized in seven patients who did not receive any rescue medication with anti-thyroid drugs (ATD), and 2/15 (13.3%) showed normal TSH. Six (40%) patients required ATD. Four of seven responders relapsed after treatment completion. Serum concentrations of thyrotropin receptor autoantibodies (TSH-R-Ab) significantly declined in all patients (mean 15.3 IU/L versus 4.0 IU/L, 66% reduction, P<0.001) and TSH-R-Ab levels normalized in four (27%). Thyroperoxidase and thyroglobulin autoantibodies significantly decreased in responders. Iscalimab rapidly reduced serum CXCL13 concentrations (P<0.001). Twelve (80.0%) patients reported at least one adverse event (AE). All treatment-related AE were mild or moderate and resolved by end of the study. CONCLUSION Iscalimab was generally safe and clinically effective in a subgroup of hyperthyroid GD patients. The potential therapeutic benefit of Iscalimab should be further tested.
Analytical separations for lipids in complex, nonpolar lipidomes using differential mobility spectrometry[S]

Secretions from meibomian glands located within the eyelid (commonly known as meibum) are rich in nonpolar lipid classes incorporating very-long (22–30 carbons) and ultra-long (>30 carbons) acyl chains. The complex nature of the meibum lipidome and its preponderance of neutral, nonpolar lipid classes presents an analytical challenge, with typically poor chromatographic resolution, even between different lipid classes. To address this challenge, we have deployed differential mobility spectrometry (DMS)-MS to interrogate the human meibum lipidome and demonstrate near-baseline resolution of the two major nonpolar classes contained therein, namely wax esters and cholesteryl esters. Within these two lipid classes, we describe ion mobility behavior that is associated with the length of their acyl chains and location of unsaturation. This capability was exploited to profile the molecular speciation within each class and thus extend meibum lipidome coverage. Intriguingly, structure-mobility relationships in these nonpolar lipids show similar trends and inflections to those previously reported for other physicochemical properties of lipids (e.g., melting point and phase-transition temperatures). Taken together, these data demonstrate that differential ion mobility provides a powerful orthoganol separation technology for the analysis of neutral lipids in complex matrices, such as meibum, and may further provide a means to predict physicochemical properties of lipids that could assist in inferring their biological function(s).
Pyrimethanil ionic liquids paired with various natural organic acid anions for reducing its adverse impacts on the environment.

In this study, nine pyrimethanil ionic liquids (PILs) were synthesized through acid-bases reaction with nine naturally derived organic acid anions, to improve the physicochemical properties and reduce the environmental adverse impacts. The PILs presented lower volatilization, higher photostability, better soil adsorption capacity, and improved fungicidal activity relative to pyrimethanil. When the length of the carbon chains in the anions was increased, the PILs showed better properties in terms of melting point, water solubility, volatility, and surface tension. The photostabilities and fungicidal activities of the PILs were significantly improved when cyclic compounds were used as the paired anion ions. With enhanced physicochemical properties and better fungicidal activity, PIL7 was selected as the best alternative to pyrimethanil. The intrinsic disadvantages of pyrimethanil could be surmounted using the system developed in the study, thus ILs could have immense potential in the development of eco-friendly and efficient fungicides in the future.
Current Principles of Motor Control, with Special Reference to Vertebrate Locomotion.

The vertebrate control of locomotion involves all levels of the nervous system from cortex to the spinal cord. Here, we aim at covering all main aspects of this complex behavior - from the operation of the microcircuits in the spinal cord to the systems and behavioral levels and extend from mammalian locomotion to the basic undulatory movements of lamprey and fish. The cellular basis of propulsion represents the core of the control system and it involves the spinal central pattern generator networks (CPGs) controlling the timing of different muscles, the sensory compensation for perturbations and the brainstem command systems controlling the level of activity of the CPGs and the speed of locomotion. The forebrain and in particular the basal ganglia are involved in determining which motor programs should be recruited at a given point of time and can both initiate and stop locomotor activity. The propulsive control system needs to be integrated with the postural control system to maintain body orientation. Moreover, the locomotor movements need to be steered so that the subject approaches the goal of the locomotor episode, or avoids colliding with elements in the environment or simply escapes at high speed. These different aspects will all be covered in the review.
Body Mass Index and Modified Glasgow Prognostic Score are Useful Predictors of Surgical Site Infection after Spinal Instrumentation Surgery: A Consecutive Series.

STUDY DESIGN Retrospective observational study. OBJECTIVE To analyze a large consecutive cohort of patients who had undergone spinal instrumentation surgery, to characterize a patient population with surgical site infections (SSI), and to identify preoperative risk factors associated with SSI. SUMMARY OF BACKGROUND DATA Malnutrition is a risk factor for SSI in many health conditions; however, the evidence connecting preoperative malnutrition with SSI in spinal instrumentation surgery is limited because of the small number of retrospective studies. While the modified Glasgow prognostic score (mGPS), C-Reactive protein (CRP)-albumin ratio (CAR), controlling nutritional status index (CONUT), prognostic nutritional index (PNI), platelet-lymphocyte ratio (PLR), and neutrophil-lymphocyte ratio (NLR) are established methods for evaluating nutritious status, little has been reported on the predictive value of these indicators with respect to postoperative spinal infection. METHODS We retrospectively investigated 384 patients who underwent spinal instrumentation surgery. We evaluated the significance of risk factors, including mGPS, CAR, CONUT, PNI, PLR, and NLR. We then performed stepwise logistic regression analysis to analyze the concurrent effects of various factors on the prevalence of SSI. RESULTS Of the 384 patients analyzed, 14 were diagnosed with SSIs. Univariate analysis showed that preoperative BMI, lymphocyte count, albumin, erythrocyte sedimentation rate, CRP, CONUT, mGPS, CAR, and PNI were risk factors for SSI. Stepwise logistic regression analysis revealed that higher mGPS and lower BMI before surgery were independent risk factors for SSI. A receiver operating characteristic curve showed that the cuff-off values of mGPS and BMI were 1 and 20.39, respectively. CONCLUSIONS The risk factors for SSI after spinal instrumentation surgery were mGPS ≧ 1 and BMI ≦ 20.39 kg/m. These findings could help to identify patients at higher risk of SSI after spinal instrumentation surgery. LEVEL OF EVIDENCE 4.
REVIEW: Obesity, neuroinflammation and reproductive function.

The increasing occurrence of obesity has become a significant public health concern. Obese individuals have higher prevalence of heart disease, stroke, osteoarthritis, diabetes, and reproductive disorders. Reproductive problems include menstrual irregularities, pregnancy complications, and infertility due to anovulation, in women, and lower testosterone and diminished sperm count, in men. In particular, obese women have reduced levels of both gonadotropin hormones and, in obese men, lower testosterone is accompanied by diminished luteinizing hormone. Together these findings indicate central dysregulation of the hypothalamus-pituitary-gonadal axis, specifically at the level of the GnRH neuron function, which is the final brain output for the regulation of reproduction. Obesity is a state of hyperinsulinemia, hyperlipidemia, hyperleptinemia, and chronic inflammation. Herein, we review recent advances in our understanding of how these metabolic and immune changes affect hypothalamic function and regulation of GnRH neuron. In the latter part, we focus on neuroinflammation as a major consequence of obesity, and discuss findings that reveal that GnRH neurons are uniquely positioned to respond to inflammatory changes.
A Survey of DevOps Concepts and Challenges

DevOpsis a collaborative and multidisciplinary organizational effort to automate continuous delivery of new software updates while guaranteeing their correctness and reliability. The present survey investigates and discusses DevOps challenges from the perspective of engineers, managers, and researchers. We review the literature and develop a DevOps conceptual map, correlating the DevOps automation tools with these concepts. We then discuss their practical implications for engineers, managers, and researchers. Finally, we critically explore some of the most relevant DevOps challenges reported by the literature.
Learning End-User Behavior for Optimized Bidding in HetNets: Impact on User/Network Association

We study the impact of end-user behavior on service provider (SP) bidding and user/network association in a HetNet with multiple SPs while considering the uncertainty in the service guarantees offered by the SPs. Using Prospect Theory (PT) to model end-user decision making that deviates from expected utility theory (EUT), we formulate user association with SPs as a multiple leader Stackelberg game where each SP offers a bid to each user that includes a data rate with a certain probabilistic service guarantee and at a given price, while the user chooses the best offer among multiple such bids. We show that when users underweight the advertised service guarantees of the SPs (a behavior observed under uncertainty), the rejection rate of the bids increases dramatically which in turn decreases the SPs utilities and service rates. To overcome this, we propose a two-stage learning-based optimized bidding framework for SPs. In the first stage, we use a support vector machine (SVM) learning algorithm to predict users' binary decisions (accept/reject bids), and then in the second stage we cast the utility-optimized bidding problem as a Markov Decision Problem (MDP) and propose a reinforcement learning-based dynamic programming algorithm to efficiently solve it. Simulation results and computational complexity analysis validate the efficiency of our proposed model.
TF-Attention-Net: An End To End Neural Network For Singing Voice Separation

In terms of source separation task, deep neural networks have two major approaches: one approach is modeling in the spectrogram domain, and the other approach is modeling in the waveform domain. Most of the previous papers use CNNs or LSTMs. However, due to the high sampling rate of audio, whether it is LSTMs with long-distance dependent or CNNs with sliding windows, it is still difficult to extract long-term input context. In this case, we propose an end-to-end network: Time-Frequency Attention Net (TF-Attention-Net), to study the ability of the attention mechanism in the source separation task. First, we introduce the Slice Attention, which can extract the acoustic features of temporal and frequency scales under different channels. Besides, the attention mechanism can be parallel calculated, while LSTMs cannot, because of its time-dependent property. Meanwhile, the receptive field of the attention mechanism is larger than the CNNs, which means that we can use shallower layers to extract longer distance dependence. Experiments indicate that our proposed TF-Attention-Net outperforms both the spectrogram-based U-Net and the waveform-based Wave-U-Net baselines.
Strategies to combat inflammation in pancreas and islet transplantation

Pancreas and islet transplantation are life-saving treatments for patients with type 1 diabetes mellitus and intractable hypoglycaemia unawareness. Donated pancreata are predominantly derived from deceased donors, most of whom have succumbed to brain death. The pancreas and islets are particularly susceptible to damage during donor brain death, and early inflammatory changes are compounded by further damage during islet isolation and intraportal infusion. The growing prevalence of T1DM and scarcity of the organ pool necessitate the development of strategies to minimise inflammatory events and improve organ quality and retrieval rates. This thesis spans three separate but related studies: evaluating the effects of isolation and anti-inflammatory treatment on isolated pancreatic islets, and modulation of inflammation in pancreas from brain-dead donors using two different anti-inflammatory approaches, one already established in clinical practice and one experimental. For this purpose, we examined isolated porcine neonatal cell clusters islets in vitro, and established porcine and murine brain death models recapitulating the human condition. Porcine neonatal islet cell clusters are considered as a potential alternative to human islets, and they are extensively utilised in experimental models. Activated protein C is a serine protease with cytoprotective, anti-apoptotic and anti-coagulant properties, which can attenuate inflammation and potentially protect islets. We hypothesized that rHuAPC could exert anti-inflammatory effects on porcine islets in culture, based on the activity of rHuAPC on tissues from several other species, and the high level of homology between porcine and human protein C and its receptor, EPCR. We studied islets from 1-3 day old piglets after isolation during 14 days of culture, measuring inflammatory
Evidence for ram-pressure stripping in a cluster of galaxies at z = 0.7

Multi-Unit Spectroscopic Explorer (MUSE) observations of the cluster of galaxies CGr32 (M200 ≃ 2 × 1014 M⊙) at z = 0.73 reveal the presence of two massive star-forming galaxies with extended tails of diffuse gas detected in the [O II]λλ3727–3729 Å emission-line doublet. The tails, which have a cometary shape with a typical surface brightness of a few 10−18 erg s−1 cm−2 arcsec−2, extend up to ≃100 kpc (projected distance) from the galaxy discs, and are not associated with any stellar component. All this observational evidence suggests that the gas was removed during a ram-pressure stripping event. This observation is thus the first evidence that dynamical interactions with the intracluster medium were active when the Universe was only half its present age. The density of the gas derived using the observed [O II]λ3729/[O II]λ3726 line ratio implies a very short recombination time, suggesting that a source of ionisation is necessary to keep the gas ionised within the tail.