Miracle-dz/UniFAR-FTUs huggingface dataset:
NMR-Based Metabolomic Approach Tracks Potential Serum Biomarkers of Disease Progression in Patients with Type 2 Diabetes Mellitus

Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by chronic hyperglycemia associated with alterations in carbohydrate, lipid, and protein metabolism. The prognosis of T2DM patients is highly dependent on the development of complications, and therefore the identification of biomarkers of T2DM progression, with minimally invasive techniques, is a huge need. In the present study, we applied a 1H-Nuclear Magnetic Resonance (1H-NMR)-based metabolomic approach coupled with multivariate data analysis to identify serum metabolite profiles associated with T2DM development and progression. To perform this, we compared the serum metabolome of non-diabetic subjects, treatment-naïve non-complicated T2DM patients, and T2DM patients with complications in insulin monotherapy. Our analysis revealed a significant reduction of alanine, glutamine, glutamate, leucine, lysine, methionine, tyrosine, and phenylalanine in T2DM patients with respect to non-diabetic subjects. Moreover, isoleucine, leucine, lysine, tyrosine, and valine levels distinguished complicated patients from patients without complications. Overall, the metabolic pathway analysis suggested that branched-chain amino acid (BCAA) metabolism is significantly compromised in T2DM patients with complications, while perturbation in the metabolism of gluconeogenic amino acids other than BCAAs characterizes both early and advanced T2DM stages. In conclusion, we identified a metabolic serum signature associated with T2DM stages. These data could be integrated with clinical characteristics to build a composite T2DM/complications risk score to be validated in a prospective cohort.
Application of Named Entity Recognition Methods to Extract Information from Echocardiography Reports

As there is no consensus about how to store the results of echocardiography examinations, information extraction from them is a non-trivial task. Successful named entity recognition (NER) is key to getting access to the stored information and the process of identification has been recognized as a bottleneck in text mining. Our goal was to develop and compare such NER methods that are capable of achieving this task. Our practical results show that the text mining-based NER method is able to perform at a similar level in finding and identifying terms as the regular expression-based NER method. The paper highlights the advantages and disadvantages of both methods.
Kinome-Wide RNA Interference Screening Identifies Mitogen-Activated Protein Kinases and Phosphatidylinositol Metabolism as Key Factors for Rabies Virus Infection

Rabies virus relies on cellular machinery for its replication while simultaneously evading the host immune response. Despite their importance, little is known about the key host factors required for rabies virus infection. Here, we focused on the human kinome, at the core of many cellular pathways, to unveil a new understanding of the rabies virus infectious cycle and to discover new potential therapeutic targets in a small interfering RNA screening. The mitogen-activated protein kinase pathway and phosphatidylinositol metabolism were identified as prominent factors involved in rabies virus infection, and those findings were further confirmed in human neurons. While bringing a new insight into rabies virus biology, we also provide a new list of host factors involved in rabies virus infection. ABSTRACT Throughout the rabies virus (RABV) infectious cycle, host-virus interactions define its capacity to replicate, escape the immune response, and spread. As phosphorylation is a key regulatory mechanism involved in most cellular processes, kinases represent a target of choice to identify host factors required for viral replication. A kinase and phosphatase small interfering RNA (siRNA) high-content screening was performed on a fluorescent protein-recombinant field isolate (Tha RABV). We identified 57 high-confidence key host factors important for RABV replication with a readout set at 18 h postinfection and 73 with a readout set at 36 h postinfection, including 24 common factors at all stages of the infection. Amongst them, gene clusters of the most prominent pathways were determined. Up to 15 mitogen-activated protein kinases (MAPKs) and effectors, including MKK7 (associated with Jun N-terminal protein kinase [JNK] signalization) and DUSP5, as well as 17 phosphatidylinositol (PI)-related proteins, including PIP5K1C and MTM1, were found to be involved in the later stage of RABV infection. The importance of these pathways was further validated, as small molecules Ro 31-8820 and PD 198306 inhibited RABV replication in human neurons. IMPORTANCE Rabies virus relies on cellular machinery for its replication while simultaneously evading the host immune response. Despite their importance, little is known about the key host factors required for rabies virus infection. Here, we focused on the human kinome, at the core of many cellular pathways, to unveil a new understanding of the rabies virus infectious cycle and to discover new potential therapeutic targets in a small interfering RNA screening. The mitogen-activated protein kinase pathway and phosphatidylinositol metabolism were identified as prominent factors involved in rabies virus infection, and those findings were further confirmed in human neurons. While bringing a new insight into rabies virus biology, we also provide a new list of host factors involved in rabies virus infection.
Social Media-based Substance Use Prediction

In this paper, we demonstrate how the state-of-the-art machine learning and text mining techniques can be used to build effective social media-based substance use detection systems. Since a substance use ground truth is difficult to obtain on a large scale, to maximize system performance, we explore different feature learning methods to take advantage of a large amount of unsupervised social media data. We also demonstrate the benefit of using multi-view unsupervised feature learning to combine heterogeneous user information such as Facebook `"likes" and "status updates" to enhance system performance. Based on our evaluation, our best models achieved 86% AUC for predicting tobacco use, 81% for alcohol use and 84% for drug use, all of which significantly outperformed existing methods. Our investigation has also uncovered interesting relations between a user's social media behavior (e.g., word usage) and substance use.
Image-Guided Radiotherapy Dose Escalation in Intermediate and High Risk Cancer Prostate Patients and Its Effect on Treatment Toxicity

Purpose: To study the effect of escalating radiation dose; in intermediate and high risk prostate cancer patients; via online image-guidance on acute toxicities. Patients and Methods: thirty-eight prostate cancer patients were treated by using simultaneous integrated boost-intensity modulated radiation therapy (SIB-IMRT) with online image guided correction via kilo voltage cone beam computed tomography (KV-CBCT)/electronic portal imaging device (EPID) of trans-rectal ultrasound (TRUS)-inserted intraprostatic gold fiduciary markers. High-risk patients received a median dose of 80.5 Gy to prostate and 56 Gy to pelvic nodes in 35 fractions over 7 weeks. Intermediate-risk patients received a similar prostate dose over the same overall treatment time. Acute toxicity (bladder, rectal and bowel symptoms) was reported once weekly during the radiation course and up to 3 months from the end of the radiation course. Results: The image guided (IG)-IMRT allows escalating the radiation dose delivered to the prostate through minimizing the margin of setup error to less than 0.5 cm with subsequent sparing of nearby organs at risk. Out of thirty-eight patients, no patient developed >grade 1 acute rectal toxicity, 7.9% of patients experienced grade 3 urinary toxicity and there was no reported small intestinal toxicity. Conclusion: Escalating the radiation dose more than 80 Gy in intermediate and high risk prostate cancer patients was safe and not associated with grade 3 - 4 RTOG toxicity when guided by online verification of intra-prostatic fiducial markers.
Towards personalized computer simulation of breast cancer treatment: a multi-scale pharmacokinetic and pharmacodynamic model informed by multi-type patient data

Mathematical modeling and simulation have emerged as a potentially powerful, time and cost effective approach to personalized cancer treatment. The usefulness of mechanistic models to disentangle complex multi-scale cancer processes such as treatment response has been widely acknowledged. However, a major barrier for multi-scale models to predict the outcomes of therapeutic regimens in a particular patient lies in their initialization and parameterization which need to reflect individual cancer characteristics accurately. In this study we use multi-type routinely acquired measurements on a single breast tumor, including histopathology, magnetic resonance imaging, and molecular profiling to personalize parts of a complex multi-scale model of breast cancer treated with chemotherapeutic and anti-angiogenic agents. We model the dynamics of drugs in tissue (pharmacokinetics) and the corresponding effects on their targets (pharmacodynamics). We developed a open-source computer program that simulates cross-sections of tumors under 12-week therapy regimes and use it to individually reproduce and elucidate treatment outcomes of four patients. For two of the tumors that did not respond to therapy, we used model simulations to suggest alternative regimes, depending on their individual characteristics, with improved outcomes. We found that more frequent doses of chemothereapy reduce tumor burden in a low proliferative tumor while lower doses of anti-angiogenic agents improve drug penetration in a poorly perfused tumor. In addition to bridge multi-type clinical data to shed light on individual treatment outcomes, our approach identified a few tumor-related aspects that need to be clinically portraited better to allow for future model-driven personalized cancer therapy.
Effect of Forced Physical Activity on the Severity of Experimental Colitis in Normal Weight and Obese Mice. Involvement of Oxidative Stress and Proinflammatory Biomarkers

Inflammatory bowel diseases are a heterogeneous group of disorders represented by two major phenotypic forms, Crohn’s disease and ulcerative colitis. Cross talk between adipokines and myokines, as well as changes in intestinal microcirculation, was proposed in pathogenesis of these disorders. C57BL/6 male mice were fed ad libitum for 12 weeks a standard (SD) or high-fat diet (HFD). After the adaptation period, two groups of animals fed SD or HFD were subjected to 6 weeks of the forced treadmill exercise and the experimental colitis was induced in both groups of sedentary and exercising mice fed SD and HFD by intra-colonic administration of 2,4,6-trinitrobenzenesulfonic acid. The disease activity index (DAI), colonic blood flow (CBF), the weight of animals, caloric intake, the mesenteric fad pad, the colonic oxidative stress markers malondialdehyde (MDA), reduced glutathione (GSH), and superoxide dismutase (SOD) activity and intestinal expression and protein content of proinflammatory markers were evaluated. Macroscopic and microscopic colitis in sedentary SD mice was accompanied by a significant fall in CBF and exacerbated in those fed a HFD. The contents of MDA, GSH, and SOD activity were significantly increased in both SD and HFD fed mice with treadmill exercise as compared with sedentary mice. In sedentary HFD mice a significant increase in the intestinal oxidative stress parameters and mucosal expression of IL-1β, TNF-α, IL-17, IFNγ, IL-6, and IL-10 protein were observed and these effects were aggravated in mice subjected to forced treadmill exercise. The mucosal expression of mRNA for TNF-α, IL-1β, iNOS, COX-2, SOD-1, SOD-2, GPx mRNAs, and the hypoxia inducible factor (HIF)-1α protein expression were upregulated in colonic mucosa of treadmill exercising HFD mice with colitis compared with those without exercise. We conclude that forced treadmill running exacerbates the severity of colonic damage in obese mice due to a fall in colonic microcirculation, an increase in oxidative stress, and the rise in expression and activity of proinflammatory biomarkers.
Solitary fibrous tumor of the thoracic spine

Solitary fibrous tumors (SFT) are uncommon mesenchymal tumors that involve the pleural cavity and numerous extrathoracic sites, including prostate, kidney, thyroid, and rarely the spinal cord. [1-6] A 58-year-old white male was admitt ed with complaints of progressive weakness and sensory disturbance of the lower extremities of 2-year duration. There was no history of fever or trauma. His bowel and bladder functions were normal. His general and systemic examination was normal. Higher mental functions, cranial nerves, and motor and sensory functions in the upper limbs were normal. Further neurologic examination revealed decreased pain, light touch, and vibration sensations below the D4 level, muscle weakness of grade 4/5 of all muscle groups in lower limbs. The deep tendon refl exes were exaggerated in both the lower limbs, and the bilateral planters were extensor. His complete blood count and relevant clinical chemistry was normal. Magnetic resonance imaging of the thoracic spine revealed a dorsally placed well-defi ned mass extending from D3 to D5 level, compressing the spinal cord. The mass was mildly hypointense on the T1-weighted images and hyperintense on T2-weighted images [Figure 1]. The patient underwent D3–D5 laminectomy and tumor extirpation. There was intradural milky-white, noncapsulated tumor dorsal to the spinal cord with a defi nite plane of cleavage between the tumor and the surrounding cord tissue. The tumor could be removed completely. Microscopic examination of the specimen revealed spindle cell proliferation. On immunohistochemical study [Figure 2], the tumor cells were positive for vimentin, but negative for bcl2— the fi ndings compatible with SFT. [1,5-8] The patient has been doing well at follow-up. SFT arising in the spinal cord needs to be diff erentiated from schwannoma, meningioma, and hemangioblastoma. [1-5] Although imaging modalities can provide a preliminary indication, the diagnosis of SFT is usually made on histology. [1,2,6,9] A careful morphologic approach and the judicious use of immunohistochemistry may assist in distinguishing them among these conditions, although some irreducible diffi culties may be faced by academics of taxonomy. [1-5] SFTs are usually indolent neoplasms Figure 1: Magnetic resonance imaging sagittal T2W images showing a hyperintense mass, placed dorsal to the cord extending from D3 to D5 level, with cord compression
Mycophenolate mofetil: a step forward in the induction treatment of ANCA-associated vasculitis? Comment on the article by Jones et al

We have read with interest the results of the MYCYC trial showing that mycophenolate mofetil (MMF) is not inferior to intravenous cyclophosphamide (CYC) in achieving a primary remission in the treatment of ANCA-associated vasculitides (AAV). 1 We would like to address several comments. First, in a previous report of the MYCYC trial in 2013, the authors could not establish a non-inferiority of MMF compared with CYC because the lower bound of the 90% CI of the absolute risk difference (RD) crossed the prespecified non-inferiority margin of −12% (MMF: n=46/70 (66%) vs CYC: n=48/70 (69%), RD=−3%, 90% CI −16% to 10%, p=0.06). 2 In the current publication, the reported primary remission rates at 6 months are slightly different compared …
Severe Acute Pancreatitis with Candida Endophthalmitis

Severe acute pancreatitis (SAP) is a risk factor for candidemia. We report a case of candida endophthalmitis in a 67-year-old man who was admitted to a hospital due to SAP with poorly controlled diabetes. After treatment for SAP, he was diagnosed with candidemia and candida endophthalmitis. We chose appropriate antifungal agents based on the results of a bacterial culture test. After treatment, the disappearance of Candida albicans (C. albicans) from the blood stream was confirmed in blood cultures. In addition, exudative plaques consistent with a fungal infection disappeared. After a diagnosis of candidemia is made, it is important to administer appropriate antifungal therapy and perform frequent ophthalmologic examinations.
Refractory postallogeneic stem cell transplant pure red cell aplasia in remission after treatment with daratumumab

patients, but two patients required red cell transfusions. The dose of carfilzomib was also reduced to 36 mg/m for patient #1. This allowed gradual improvement of hemoglobin and partial normalization of mean cell volume over the following cycles of treatment. Other patients were able to continue the same dose of carfilzomib. The blood features described persisted throughout the duration of their treatment. None of the patients had any other cause for the changes identified. Two patients who did not receive trimethoprim-sulfamethoxazole PJP prophylaxis still developed oxidative hemolysis with comparable severity, and patient #1 had received the same prophylaxis during previous treatment without any issues. We have not observed oxidative hemolysis in many other patients treated with trimethoprim-sulfamethoxazole. This case series outlines the novel finding of oxidative hemolytic anemia in eight patients receiving 56 mg/m carfilzomib-based therapy in three different treatment schemes, in the absence of other causes including supportive medications and G6PD deficiency. We believe this is the main mechanism of carfilzomib-induced anemia. While we observed mostly well compensated anemia, we recommend consideration of dose reduction of carfilzomib in severe and/or symptomatic cases. We now routinely screen our patients for G6PD deficiency prior to commencing high dose carfilzomib, an especially important consideration for high prevalence areas. Similarly, scrutinization of the medication history for other sources of oxidative stress should be performed routinely prior to treatment.
Extending Markov Chain Monte Carlo with People to categories defined on sets of discrete items

A recently-developed method known as Markov Chain Monte Carlo for People (MCMCP) has been shown to be successful at measuring how people represent categories. The original MCMCP method could only be used for categories defined over stimuli that can be described by a fixed set of parameters. However, the objects that belong to real world categories – such as images or documents – are often not easy to describe in parametric terms. Here we introduce an extension we call discrete-MCMCP, which can be used to estimate people’s category representations over an arbitrary discrete set of stimuli. This significantly extends the scope of the method, making it possible to apply it to large image databases, sets of documents, and other stimuli that are hard to parameterize. We present experimental results showing that performance is similar to that of the original method when applied to a set of stimuli for which a parametric representation can be found, and demonstrating the flexibility of discrete-MCMCP by estimating natural categories using a set of 4000 images drawn from online databases.
Where to begin? Sigma factors and the selectivity of transcription initiation in bacteria

Transcription is the fundamental process that enables the expression of genetic information. DNA‐directed RNA polymerase (RNAP) uses one strand of the DNA duplex as template to produce complementary RNA molecules that serve in translation (rRNA, tRNA), protein synthesis (mRNA) and regulation (sRNA). Although the RNAP core is catalytically competent for RNA synthesis, the selectivity of transcription initiation requires a sigma (σ) factor for promoter recognition and opening. Expression of alternative σ factors provides a powerful mechanism to control the expression of discrete sets of genes (a σ regulon) in response to specific nutritional, developmental or stress‐related signals. Here, I review the key insights that led to the original discovery of σ factor 50 years ago and the subsequent discovery of alternative σ factors as a ubiquitous mechanism of bacterial gene regulation. These studies form a prelude to the more recent, genomics‐enabled insights into the vast diversity of σ factors in bacteria.
Glucose Signaling in Saccharomyces cerevisiae

SUMMARY Eukaryotic cells possess an exquisitely interwoven and fine-tuned series of signal transduction mechanisms with which to sense and respond to the ubiquitous fermentable carbon source glucose. The budding yeast Saccharomyces cerevisiae has proven to be a fertile model system with which to identify glucose signaling factors, determine the relevant functional and physical interrelationships, and characterize the corresponding metabolic, transcriptomic, and proteomic readouts. The early events in glucose signaling appear to require both extracellular sensing by transmembrane proteins and intracellular sensing by G proteins. Intermediate steps involve cAMP-dependent stimulation of protein kinase A (PKA) as well as one or more redundant PKA-independent pathways. The final steps are mediated by a relatively small collection of transcriptional regulators that collaborate closely to maximize the cellular rates of energy generation and growth. Understanding the nuclear events in this process may necessitate the further elaboration of a new model for eukaryotic gene regulation, called “reverse recruitment. ” An essential feature of this idea is that fine-structure mapping of nuclear architecture will be required to understand the reception of regulatory signals that emanate from the plasma membrane and cytoplasm. Completion of this task should result in a much improved understanding of eukaryotic growth, differentiation, and carcinogenesis.
Verbal Fluency in Patients Receiving Bilateral versus Left-Sided Deep Brain Stimulation of the Subthalamic Nucleus for Parkinson's Disease

Abstract The purpose of this study was to investigate the relative effects of unilateral (left-sided) versus bilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN) on verbal fluency. To do this, 10 Parkinson's disease patients with predominantly bilateral motor symptoms who received bilateral STN DBS were compared with 6 patients suffering from predominantly unilateral symptoms who received STN DBS on the left side only. The results suggest that unilateral STN DBS of the speech dominant hemisphere is associated with significantly less declines in measures of verbal fluency as compared to bilateral stimulation. (JINS, 2012, 18, 606–611)