Miracle-dz/UniFAR-FTUs huggingface dataset:
FTO promotes proliferation and migration of bladder cancer via enhancing stability of STAT3 mRNA in an m6A-dependent manner

ABSTRACT N6-Methyladenosine (m6A) plays a key role in the occurrence and development of various cancers. Fat mass and obesity‐associated protein (FTO) was is involved in multiple cancers owing to its demethylase activity, and the molecular mechanism underlying FTO-promoted bladder cancer proliferation and migration via the regulation of RNA stability requires further investigation. In the present study, FTO was upregulated in bladder cancer and related to poor prognosis. Gain- and loss-of-function experiments showed that the upregulation of FTO promoted bladder cancer proliferation and migration. Mechanistic studies showed that FTO enhanced the stability of signal transducer and activator of transcription 3 (STAT3) mRNA in an m6A-dependent manner, thereby increasing STAT3 expression, which subsequently promoted P-STAT3 expression and activated STAT3 signalling pathway. Overall, this study revealed that the critical role of FTO in the progression of bladder cancer and could provide a novel avenue to regulate oncogene STAT3.
Within-person fluctuations over three years in depression, anxiety, fatigue, and health-related quality of life in multiple sclerosis

Background: Longitudinal studies of health-related quality of life (HRQoL) in multiple sclerosis (MS) are limited. Most have examined average changes within the population, rather than dynamic changes within individuals. Objective: To assess the between- and within-individual association between depression, anxiety, fatigue, cognition, physical functioning, and physical comorbidities and HRQoL. Methods: Adults with MS underwent physical and cognitive assessments and reported symptoms of fatigue (Daily Fatigue Impact Scale), depression and anxiety (Hospital Anxiety and Depression Scale (HADS)), and HRQoL (RAND-36) annually (n = 4 visits). We evaluated associations of elevated symptoms of anxiety (HADS-A) and depression (HADS-D), fatigue, physical function (timed-walk and nine-hole peg test), cognitive function and comorbidity count with physical (PCS-36) and mental (MCS-36) HRQoL using multivariable linear models—estimating between-person and within-person effects. Results: Of 255 participants with MS enrolled, 81.6% were women. After adjustment, within-person increases in depression and fatigue were associated with decreases in physical HRQoL. Increases in depression, anxiety, and comorbidity count were associated with decreases in mental HRQoL. Conclusions: Within-person increases in symptoms of depression, anxiety and fatigue, and comorbidity count are associated with HRQoL decreases among adults with MS, highlighting the potential magnitude of individual benefit of intervention for these symptoms.
Novel molecular hybrid geometric-harmonic-Zagreb degree based descriptors and their efficacy in QSPR studies of polycyclic aromatic hydrocarbons

ABSTRACT The physicochemical characteristics of polycyclic aromatic compounds critical to environmental modelling such as octanol partition coefficients, solubility, lipophilicity, polarity and several equilibrium constants are functions of their underlying molecular structures, prompting the development of mathematical models to predict such characteristics for which experimental results are difficult to obtain. We propose twelve novel descriptors derived from geometric, harmonic and Zagreb degree-based descriptors and then test the effectiveness of these descriptors on a data set consisting of 55 benzenoid hydrocarbons of environmental importance. Our computations show that the proposed descriptors have a good linear correlation and predictive power when compared to the degree and distance type descriptors. We have also derived the QSPR expressions for four properties of a large series of polycyclic aromatics arising from circumscribing coronenes and show that a scaling factor can be deduced to derive physicochemical properties of such series up to 2D graphene sheets.
Characterization of a novel interaction of the Nup159 nucleoporin with asymmetrically localized spindle pole body proteins and its link with autophagy

Both the spindle microtubule-organizing centers and the nuclear pore complexes (NPCs) are convoluted structures where many signaling pathways converge to coordinate key events during cell division. Interestingly, despite their distinct molecular conformation and overall functions, these structures share common components and collaborate in the regulation of essential processes. We have established a new link between microtubule-organizing centers and nuclear pores in budding yeast by unveiling an interaction between the Bfa1/Bub2 complex, a mitotic exit inhibitor that localizes on the spindle pole bodies, and the Nup159 nucleoporin. Bfa1/Bub2 association with Nup159 is reduced in metaphase to not interfere with proper spindle positioning. However, their interaction is stimulated in anaphase and assists the Nup159-dependent autophagy pathway. The asymmetric localization of Bfa1/Bub2 during mitosis raises the possibility that its interaction with Nup159 could differentially promote Nup159-mediated autophagic processes, which might be relevant for the maintenance of the replicative lifespan.
Repurposing Antihypertensive and Statin Medications for Spinal Pain

Study Design. Mendelian randomization (MR) study. Objective. To examine whether antihypertensive medications (beta-blockers, calcium channel blockers, and angiotensin-converting enzyme inhibitors) and statins can be repurposed to prevent or treat spinal pain (back or neck pain). Summary of Background Data. Observational studies and a recent MR study have found associations between elevated blood pressure and a greater risk of back pain. Observational studies have found associations between hyperlipidemia and statin use and greater risk of back pain. No prior MR studies have examined the effects of antihypertensives or statins on spinal pain. Materials and Methods. This was a two-sample MR study using publicly available summary statistics from large-scale genome-wide association studies (GWAS). Sample sizes in exposure GWASs were n=757,601 (systolic blood pressure) and n=173,082 (low-density lipoprotein cholesterol), and n=1,028,947 for the outcome GWAS of spinal pain defined as health care seeking for any spinal pain-related diagnosis. Genes and cis-acting variants were identified as proxies for the drug targets of interest. MR analyses used inverse-variance weighted meta-analysis. The threshold for statistical significance after correction for multiple testing was P<0.0125. Results. No statistically significant associations of these medications with spinal pain were found. However, findings were suggestive of a protective effect of beta-blockers on spinal pain risk (odds ratio [OR] 0.84, 95% confidence interval [CI] 0.72–0.98; P=0.03), and calcium channel blockers on greater spinal pain risk (OR 1.12, 95% CI 1.02–1.24; P=0.02). Conclusions. A protective effect of beta-blockers on spinal pain was suggested in the current study, consistent with findings from observational studies of various other pain phenotypes. The detrimental effect of calcium channel blockers on spinal pain suggested in the current study must be interpreted in the context of conflicting directions of effect on nonspinal pain phenotypes in other observational studies. This Mendelian randomization study examined whether antihypertensive medications (beta-blockers, calcium channel blockers, and angiotensin-converting enzyme inhibitors) and statins can be repurposed to prevent or treat spinal. This was a two-sample MR study using publicly available summary statistics from large-scale genome-wide association studies ranging size from 173,082 to 1,028,947 adults. While no statistically significant associations were found, a protective effect of beta-blockers on spinal pain was suggested (odds ratio [OR] 0.84, 95% confidence interval [CI] 0.72 to 0.98; p= 0.03), as was a detrimental effect of calcium channel blockers on spinal pain (OR 1.12, 95% CI 1.02 to 1.24; p= 0.02).
Timely Diagnosis of Incubating Syphilis Infections Using Treponema pallidum Transcription-Mediated Amplification Assay

Abstract Background Syphilis is a complex, multistage, sexually transmitted infection (STI) caused by the bacterium Treponema pallidum subspecies pallidum (TP). New diagnostic tools are needed to minimize transmission. In this study, we aimed to assess the additional value of an investigational transcription-mediated amplification test for TP (TP-TMA) for routine diagnostics. Methods Between September 2021 and August 2022, visits by all participants of the national preexposure prophylaxis (PrEP) program at the sexual health center (SHC) in Amsterdam were included. Anal, pharyngeal, vaginal, and urine samples collected for Chlamydia trachomatis and Neisseria gonorrhoeae screening were additionally tested with the TP-TMA assay based on detection of 23S rRNA of TP. Results In total, 9974 SHC visits by 3283 participants were included. There were 191 infectious syphilis cases diagnosed: 26 (14%) primary syphilis, 54 (29%) secondary syphilis, and 111 (58%) early latent syphilis. In 79 of the 191 (41%) syphilis cases, at least 1 sample was TP-TMA–positive. For 16 participants, the positive TP-TMA result was not concordant with routine diagnostics. Of those, 2 participants were treated for syphilis within a week before the visit. Eight participants were treated for a syphilis notification at the visit or for another STI. Five participants were diagnosed with syphilis at the following visit, and 1 participant was lost to follow-up. Conclusions By adding the TP-TMA assay to routine diagnostics, we identified 14 of 191 (7%) additional syphilis infections among participants of the national PrEP program. The TP-TMA assay is a useful diagnostic tool to increase syphilis case finding and thus limit the transmission of syphilis.
How safe is the treatment of pregnant women with fear of childbirth using eye movement desensitization and reprocessing therapy? Obstetric outcomes of a multi‐center randomized controlled trial

Pregnant women with fear of childbirth display an elevated risk of a negative delivery experience, birth‐related post‐traumatic stress disorder, and adverse perinatal outcomes such as preterm birth, low birthweight, and postpartum depression. One of the therapies used to treat fear of childbirth is eye movement desensitization and reprocessing (EMDR) therapy. The purpose of the present study was to determine the obstetric safety and effectiveness of EMDR therapy applied to pregnant women with fear of childbirth.
Advances in computational methods for Quantum Field Theory calculations

This PhD thesis is the result of work I performed as part of the HEPGAME (High Energy Physics and Games) project. The HEPGAME project is supported by the ERC Advanced Grant no. 320651 and its primary goal is to apply methods from artificial intelligence to solve problems in high energy physics. The symbolic manipulation toolkit Form plays a key role in the investigation. During the PhD I worked in three different locations. The first half year I mostly worked at Tilburg University. The next few years I have worked at Leiden University and Nikhef. At Leiden University, I taught a course, supervised a student, and worked on the computer science aspect of this thesis with my close colleagues Jaap van den Herik, Aske Plaat, and Ali Mirsoleimani. This mainly involved expression simplification, which turned into chapter 2. At Nikhef, I focused on physics, and worked on designing computer programs with my close colleagues Jos Vermaseren and Takahiro Ueda. This resulted in the Forcer program, described in chapter 3. Later, Andreas Vogt joined to compute new physical quantities with Forcer. The results formed the basis of chapter 4. Together with Franz Herzog we decided to aim for something we had not thought possible: computing the five-loop beta function. After a year of puzzling, we understood the R∗-method which could help us achieve our goal. The method is explained in chapter 5. Finally, after combining the Forcer program and the computer code for the R∗-method, we were able to compute the five-loop beta function for Yang-Mills theory with fermions. This formed the basis for chapter 6. I have had the pleasure to work with experts in the fields of Artificial Intelligence, Computer Science, and Theoretical Physics. This enriching experience has helped shape this thesis, for which I am grateful.
Osteopontin characterizes bile duct–associated macrophages and correlates with liver fibrosis severity in primary sclerosing cholangitis

Background and Aims: Primary sclerosing cholangitis (PSC) is an immune-mediated cholestatic liver disease for which pharmacological treatment options are currently unavailable. PSC is strongly associated with colitis and a disruption of the gut-liver axis, and macrophages are involved in the pathogenesis of PSC. However, how gut-liver interactions and specific macrophage populations contribute to PSC is incompletely understood. Approach and Results: We investigated the impact of cholestasis and colitis on the hepatic and colonic microenvironment, and performed an in-depth characterization of hepatic macrophage dynamics and function in models of concomitant cholangitis and colitis. Cholestasis-induced fibrosis was characterized by depletion of resident KCs, and enrichment of monocytes and monocyte-derived macrophages (MoMFs) in the liver. These MoMFs highly express triggering-receptor-expressed-on-myeloid-cells-2 (Trem2) and osteopontin (Spp1), markers assigned to hepatic bile duct-associated macrophages, and were enriched around the portal triad, which was confirmed in human PSC. Colitis induced monocyte/macrophage infiltration in the gut and liver, and enhanced cholestasis-induced MoMF-Trem2 and Spp1 upregulation, yet did not exacerbate liver fibrosis. Bone marrow chimeras showed that knockout of Spp1 in infiltrated MoMFs exacerbates inflammation in vivo and in vitro, while monoclonal antibody–mediated neutralization of SPP1 conferred protection in experimental PSC. In human PSC patients, serum osteopontin levels are elevated compared to control, and significantly increased in advanced stage PSC and might serve as a prognostic biomarker for liver transplant-free survival. Conclusions: Our data shed light on gut-liver axis perturbations and macrophage dynamics and function in PSC and highlight SPP1/OPN as a prognostic marker and future therapeutic target in PSC.
Pharmacological prophylaxis with pyridostigmine bromide against nerve agents adversely impact on airway function in an ex vivo rat precision-cut lung slice model

Abstract The carbamate pyridostigmine bromide (PB) is the only fielded pharmacological prophylaxis for military use against nerve agents. Previous studies have shown differences in the PB-pretreatment efficacy for various nerve agents and in the influence of post-exposure treatment with common antidotes. In the present study, the aim was to evaluate the possibility of using an ex vivo rat precision-cut lung slice model to determine the impact of PB pretreatment on VX-induced bronchoconstriction. In addition, the efficacy of post-exposure treatment with atropine sulfate following PB-prophylaxis was investigated. Bronchoconstriction was induced by electric-field stimulation and was significantly aggravated by 10 µM PB. Airway recovery was decreased by both 1 and 10 µM PB. Evaluation of acetylcholineesterese inhibition by PB showed that the lower concentration met the clinical criteria of residual enzyme activity while the higher concentration completely inhibited the activity. Exposure to VX with or without pretreatment demonstrated similar contractions. However, VX-incubation following pretreatment caused decreased airway relaxation compared to pretreatment alone. Atropine treatment following PB- and VX-exposure significantly decreased the maximum airway contraction and increased the relaxation. In conclusion, no beneficial effect of PB-prophylaxis on VX-induced contractions was observed. The atropine efficacy to relax airways was significant demonstrating the importance of efficient post-exposure therapeutics to protect against the life-threatening respiratory contractions.
Dehazing via graph cut

Abstract. Transmission map estimation is one of the most important parts of single image dehazing, which is known as an under-constraint problem. Various assumptions, some have been summarized as priors or models, are proposed to solve this problem. However, many previous methods cannot honestly reflect their theory in the results, due to not considering all of the employed assumptions simultaneously. Meanwhile, most other methods avoiding this defect are with inappropriate assumptions. We try to solve this problem by proposing a method that simultaneously considers the dark channel prior and the piecewise smoothness assumption. It is achieved by minimizing an energy function based on all of the employed assumptions. To maintain a reasonable run time, the minimization problem is mapped into a graph cut problem with a specific graph build strategy. The method is compared with state-of-the-art methods on both synthetic and natural images. Experimental results show that the proposal is promising for haze removal quality.
Tunable and white light photoluminescence from ZnO on porous Si with the addition of carbon quantum dots

In this work we demonstrate a two-pixel solid-state photoluminescent device able to emit white light covering the entire visible spectrum from 380 nm up to 800 nm. The device is based on a combination of porous Si, hydrothermally grown ZnO and carbon quantum dots, in a two-pixel formation, with porous Si and ZnO acting independently while the carbon quantum dots are deposited on top of the entire device. All processing is done using standard Si processing techniques. Moreover, the device design allows for tunability of the emitted spectrum simply by choosing the desired combination of the materials. Overall, the demonstrated device is low cost, environmentally safe and biocompatible.
Adaptive Bayesian semiparametric density estimation in sup-norm

We investigate the problem of deriving adaptive posterior rates of contraction on $L^{\infty}$ balls in density estimation. Although it is known that log-density priors can achieve optimal rates when the true density is sufficiently smooth, adaptive rates were still to be proven. Recent works have shown that the so called spike-and-slab priors can achieve optimal rates of contraction under $L^{\infty}$ loss in white-noise regression and multivariate regression with normal errors. Here we show that a spike-and-slab prior on the log-density also allows for (nearly) optimal rates of contraction in density estimation under $L^{\infty}$ loss. Interestingly, our results hold without lower bound on the smoothness of the true density.
Fucoidan from Fucus vesiculosus: Evaluation of the Impact of the Sulphate Content on Nanoparticle Production and Cell Toxicity

The composition of seaweeds is complex, with vitamins, phenolic compounds, minerals, and polysaccharides being some of the factions comprising their structure. The main polysaccharide in brown seaweeds is fucoidan, and several biological activities have been associated with its structure. Chitosan is another marine biopolymer that is very popular in the biomedical field, owing to its suitable features for formulating drug delivery systems and, particularly, particulate systems. In this work, the ability of fucoidan to produce nanoparticles was evaluated, testing different amounts of a polymer and using chitosan as a counterion. Nanoparticles of 200–300 nm were obtained when fucoidan prevailed in the formulation, which also resulted in negatively charged nanoparticles. Adjusting the pH of the reaction media to 4 did not affect the physicochemical characteristics of the nanoparticles. The IC50 of fucoidan was determined, in both HCT−116 and A549 cells, to be around 160 µg/mL, whereas it raised to 675–100 µg/mL when nanoparticles (fucoidan/chitosan = 2/1, w/w) were tested. These marine materials (fucoidan and chitosan) provided features suitable to formulate polymeric nanoparticles to use in biomedical applications.
Sentiment classification of documents in Serbian: The effects of morphological normalization and word embeddings

An open issue in the sentiment classification of texts written in Serbian is the effect of different forms of morphological normalization and the usefulness of leveraging large amounts of unlabeled texts. In this paper, we assess the impact of lemmatizers and stemmers for Serbian on classifiers trained and evaluated on the Serbian Movie Review Dataset. We also consider the effectiveness of using word embeddings, generated from a large unlabeled corpus, as classification features.
“I don’t think you can really understand it until you put it to action”: school-based SLPs’ reflections on graduate and continuing education in AAC

Abstract Graduate programs have made strides to improve augmentative and alternative communication (AAC) learning opportunities for pre-service speech-language pathologists (SLPs). In addition, a number of continuing education opportunities are available to practicing SLPs; however, many still report feeling underprepared to serve clients with AAC needs. The purpose of this study was to describe school-based SLPs’ perspectives regarding their graduate training, on-the-job experience, and ongoing professional development needs related to AAC. Semi-structured interviews were completed with 17 school-based SLPs. Interviews were recorded and transcribed verbatim. Using a phenomenological approach, key themes emerged related to AAC knowledge and skills including a need for SLPs to rely on a framework for decision making, the importance of interprofessional training, and difficulties with staying abreast of new technology. The researchers present recommendations of principles and concepts for instructors to include in graduate AAC courses, as well as professional development considerations.
Peroral endoscopic myotomy compared to laparoscopic Heller myotomy and pneumatic dilation in the treatment of achalasia: a systematic review

Abstract Peroral endoscopic myotomy (POEM) is an intervention for the treatment of achalasia which has gained popularity over the last decade. It’s efficacy and invasiveness are comparable to laparoscopic Heller myotomy (LHM). The purpose of this systematic review is to compare POEM to existing therapies. The systematic review was performed following the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. MEDLINE, EMBASE, Web of Science and Cochrane Libraries were searched using keywords: esophageal achalasia, POEM, LHM, pneumatic dilation (PD), and related terms. The studied outcomes were Eckardt score, clinical success, hospital stay, cost-utility analysis, complications, and post-treatment gastro-esophageal reflux disease. Articles were reviewed by one researcher and uncertainty was resolved by a second researcher. The search strategy retrieved 1948 citations. After removing duplicates and applying the exclusion criteria, 91 studies were selected for full-text review of which a total of 31 studies were considered eligible for further analysis, including two studies which were found through manual searching. POEM has improved efficacy compared to PD with similar cost-effectiveness. POEM results showed comparable patient outcomes when compared with laparoscopic myotomy. Overall, POEM is a feasible first-line treatment for achalasia.