Miracle-dz/UniFAR-FTUs huggingface dataset:
Expression of six3 and otx in Solenogastres (Mollusca) supports an ancestral role in bilaterian anterior‐posterior axis patterning

The homeodomain transcription factors six3 and otx are involved in patterning the anterior body and parts of the central nervous system (CNS) in bilaterians. Their similar expression patterns have been used as an argument for homology of heads, brains, segmentation, and ciliated larvae. We investigated the developmental expression of six3 and otx in the aplacophoran mollusk Wirenia argentea. Six3 is expressed in subepithelial cells delimiting the apical organ of the solenogaster pericalymma larva. Otx is expressed in cells of the prototroch and adjacent regions as well as in posterior extensions of the prototrochal expression domain. Advanced larvae also show pretrochal otx expression in the developing CNS. Comparative analysis of six3 and otx expression in bilaterians argues for an ancestral function in anterior‐posterior body axis patterning but, due to its presence in animals lacking a head and/or a brain, not necessarily for the presence of these morphological structures in the last common ancestor (LCA) of bilaterians. Likewise, the hypothesis that the posterior border of otx expression corresponds to the border between the unsegmented head and the segmented trunk of the LCA of protostomes is not supported, since otx is extensively expressed in the trunk in W. argentea and numerous other protostomes.
A Comparative Evaluation of Unsupervised Anomaly Detection Algorithms for Multivariate Data

Anomaly detection is the process of identifying unexpected items or events in datasets, which differ from the norm. In contrast to standard classification tasks, anomaly detection is often applied on unlabeled data, taking only the internal structure of the dataset into account. This challenge is known as unsupervised anomaly detection and is addressed in many practical applications, for example in network intrusion detection, fraud detection as well as in the life science and medical domain. Dozens of algorithms have been proposed in this area, but unfortunately the research community still lacks a comparative universal evaluation as well as common publicly available datasets. These shortcomings are addressed in this study, where 19 different unsupervised anomaly detection algorithms are evaluated on 10 different datasets from multiple application domains. By publishing the source code and the datasets, this paper aims to be a new well-funded basis for unsupervised anomaly detection research. Additionally, this evaluation reveals the strengths and weaknesses of the different approaches for the first time. Besides the anomaly detection performance, computational effort, the impact of parameter settings as well as the global/local anomaly detection behavior is outlined. As a conclusion, we give an advise on algorithm selection for typical real-world tasks.
Comparison of independent and dependent culture methods for the detection of transient bacteremia in diabetic subjects with chronic periodontitis.

INTRODUCTION Oral-derived bacteremia may occur after several dental procedures and routine daily activities. Some conditions of the oral cavity may favor episodes of bacteremia. This would be the case of patients with diabetes mellitus and periodontitis, who exhibit exacerbated gingival inflammation and may be more prone to developing oral-derived bacteremia. OBJECTIVE To compare the effectiveness of an independent culture method (quantitative real-time PCR- qCR) and the most commonly used method (BacT-ALERT 3D®) for the diagnosis of bacteremia. MATERIALS AND METHODS Blood samples were drawn from subjects with type 2 diabetes mellitus and chronic periodontitis before and after apple chewing. Samples were processed by an automated blood culture system (BacT-ALERT 3D®) monitored for 15 days with suitable subculture of positive cultures. In parallel, whole DNA from blood samples was purified using a commercial kit and screened by qPCR using a universal primer set of16S rDNA for bacteria detection. RESULTS Blood cultures taken before apple chewing were shown to be negative by the two diagnostic methods. After chewing, two samples (11%) showed bacterial growth by BacT-ALERT 3D® whereas qPCR did not detect the presence of bacteria in any sample. CONCLUSIONS qPCR did not show greater effectiveness than the BacT-ALERT 3D® in the detection of bacteremia of oral origin.
Efficacy of Low-Intensity Extracorporeal Shock Wave Therapy on Men With Chronic Pelvic Pain Syndrome Refractory to 3-As Therapy

Managing patients with chronic pelvic pain syndrome (CPPS) refractory to the traditional 3-As therapy (antibiotics, alpha-blockers, and anti-inflammatories) is a challenging task. Low-intensity extracorporeal shock wave therapy (LI-ESWT) was recently reported to be able to improve pain, urinary symptoms, and even sexual function by inducing neovascularization and anti-inflammation, reducing muscle tone, and influencing nerve impulses. This study evaluates whether combined treatment with LI-ESWT can restore clinical ability and quality of life (QoL) in patients refractory to 3-As therapy. This was an open-label, single-arm prospective study. Patients with CPPS without more than a 6-point decrease in the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) total score under the maximal dosage of 3-As therapy were enrolled. LI-ESWT treatment consisted of 3,000 shock waves administered once weekly for 4 weeks. The NIH-CPSI, visual analog scale (VAS) score, International Prostate Symptom Score (IPSS), and the five-item version of the International Index of Erectile Function (IIEF-5) were used to evaluate efficacy at 1, 4, and 12 weeks after LI-ESWT. Thirty-three patients were enrolled in this study. After LI-ESWT treatment, 27 of the 33 patients (81.82%) had a successful response to LI-ESWT, with a decrease of 3.29 and 5.97 in the VAS score and total IPSS at the 3-month follow-up. Waist circumference was the only significant predictor of a successful response to LI-ESWT. LI-ESWT can serve as a salvage therapy for patients with CPPS refractory to traditional 3-As therapy. Further studies are needed to determine an adequate therapeutic protocol and important predictors in patients with different CPPS etiologies.
Gabapentin for Perioperative Analgesia in Otorhinolaryngology–Head and Neck Surgery

Objective Recent research has investigated the role of gabapentin in perioperative pain relief in otorhinolaryngology–head and neck surgery. This review aims to identify whether sufficient evidence exists for the routine use of gabapentin in the perioperative setting. Data Sources MEDLINE, Cochrane CENTRAL, EMBASE, and Google Scholar. Review Methods A comprehensive systematic search was performed with keywords for articles up to November 2015. The systematic review included all randomized, placebo-, and active-controlled trials investigating the role of perioperative gabapentin for pain in otorhinolaryngology–head and neck surgery. The studies were assessed for risk of bias and selected and reviewed by the main author. Selected trials were required to have data in the form of pain intensity scores, analgesic consumption, adverse effects, or return to normal function. Results A total of 14 randomized controlled trials were included, of which 4 had an active control. The placebo-controlled trials included 4 for tonsillectomy, 3 for rhinology, and 3 for thyroidectomy. These studies were not suitable for meta-analysis. Trial quality involving gabapentin in tonsillectomy surgery is variable. The higher-quality studies reported significantly reduced analgesic consumption in the gabapentin groups, with the effect on pain scores less clear. There was a significant benefit, within the first 24 hours, in pain and analgesic consumption as compared with placebo favoring the gabapentin groups following rhinologic and thyroid surgery. Conclusion Overall, gabapentin appears to have a significant beneficial effect on perioperative pain relief and analgesic consumption in otorhinolaryngology–head and neck surgery procedures within the first 24 hours.
Rainfall during parental care reduces reproductive and survival components of fitness in a passerine bird

Adverse weather conditions during parental care may have direct consequences for offspring production, but longer-term effects on juvenile and parental survival are less well known. We used long-term data on reproductive output, recruitment, and parental survival in northern wheatears (Oenanthe oenanthe) to investigate the effects of rainfall during parental care on fledging success, recruitment success (juvenile survival), and parental survival, and how these effects related to nestling age, breeding time, habitat quality, and parental nest visitation rates. While accounting for effects of temperature, fledging success was negatively related to rainfall (days > 10 mm) in the second half of the nestling period, with the magnitude of this effect being greater for breeding attempts early in the season. Recruitment success was, however, more sensitive to the number of rain days in the first half of the nestling period. Rainfall effects on parental survival differed between the sexes; males were more sensitive to rain during the nestling period than females. We demonstrate a probable mechanism driving the rainfall effects on reproductive output: Parental nest visitation rates decline with increasing amounts of daily rainfall, with this effect becoming stronger after consecutive rain days. Our study shows that rain during the nestling stage not only relates to fledging success but also has longer-term effects on recruitment and subsequent parental survival. Thus, if we want to understand or predict population responses to future climate change, we need to consider the potential impacts of changing rainfall patterns in addition to temperature, and how these will affect target species' vital rates.
Single‐dose pharmacokinetics of co‐crystal of tramadol–celecoxib: Results of a four‐way randomized open‐label phase I clinical trial in healthy subjects

Aims Co‐crystal of tramadol–celecoxib (CTC) is a novel co‐crystal molecule containing two active pharmaceutical ingredients under development by Esteve (E‐58425) and Mundipharma Research (MR308). This Phase I study compared single‐dose pharmacokinetics (PK) of CTC with those of the individual reference products [immediate‐release (IR) tramadol and celecoxib] alone and in open combination. Methods Healthy adults aged 18–55 years were orally administered four treatments under fasted conditions (separated by 7‐day wash‐out period): 200 mg IR CTC (equivalent to 88 mg tramadol and 112 mg celecoxib; Treatment 1); 100 mg IR tramadol (Treatment 2); 100 mg celecoxib (Treatment 3); and 100 mg IR tramadol and 100 mg celecoxib (Treatment 4). Treatment sequence was assigned using computer‐generated randomization. PK parameters were calculated using noncompartmental analysis with parameters for CTC adjusted according to reference product dose (100 mg). Results Thirty‐six subjects (28 male, mean age 36 years) participated. Tramadol PK parameters for Treatments‐1, –2 and –4, respectively, were 263, 346 and 349 ng ml–1 (mean maximum plasma concentration); 3039, 2979 and 3119 ng h ml–1 (mean cumulative area under the plasma concentration–time curve); and 2.7, 1.8 and 1.8 h (median time to maximum plasma concentration). For Treatments 1, 3 and 4, the respective celecoxib PK parameters were 313, 449 and 284 ng ml–1; 2183, 3093 and 2856 ng h ml–1; and 1.5, 2.3 and 3.0 h. No unexpected adverse events were reported. Conclusion PK parameters of each API in CTC were modified by co‐crystallization compared with marketed formulations of tramadol, celecoxib, and their open combination.
Efficient derivation of stable primed pluripotent embryonic stem cells from bovine blastocysts

Significance Embryonic stem cells (ESCs) are derived from the inner cell mass of a preimplantation blastocyst, as has been well established in rodents and primates. To date, however, the derivation and stable propagation of pluripotent ESCs from domestic ungulates remain unsuccessful. The production of ESCs from large livestock species is important for genomic testing and selection, genome engineering, and studying human diseases. Here, we report that stable bovine ESCs can be efficiently derived in a culture condition based on Wnt-pathway inhibition. These well-characterized ESC lines not only will enrich our understanding of pluripotency programs in the ungulate species but also will provide a useful resource for the creation of transgenic ungulate models of human diseases. Embryonic stem cells (ESCs) are derived from the inner cell mass of preimplantation blastocysts. From agricultural and biomedical perspectives, the derivation of stable ESCs from domestic ungulates is important for genomic testing and selection, genome engineering, and modeling human diseases. Cattle are one of the most important domestic ungulates that are commonly used for food and bioreactors. To date, however, it remains a challenge to produce stable pluripotent bovine ESC lines. Employing a culture system containing fibroblast growth factor 2 and an inhibitor of the canonical Wnt-signaling pathway, we derived pluripotent bovine ESCs (bESCs) with stable morphology, transcriptome, karyotype, population-doubling time, pluripotency marker gene expression, and epigenetic features. Under this condition bESC lines were efficiently derived (100% in optimal conditions), were established quickly (3–4 wk), and were simple to propagate (by trypsin treatment). When used as donors for nuclear transfer, bESCs produced normal blastocyst rates, thereby opening the possibility for genomic selection, genome editing, and production of cattle with high genetic value.
Breast cancer cell-derived exosomes and macrophage polarization are associated with lymph node metastasis

Crosstalk between breast cancer and macrophages has potential implications for tumor metastasis. This study investigates macrophage polarization induced by triple-negative breast cancer (TNBC) cell-derived exosomes that promote lymph node (LN) metastasis in orthotopic TNBC models. The MDA-MB-231 cancer cell line expressing the exosomal CD63-red fluorescence (RFP) fusion protein was generated to noninvasively visualize exosome transfer into cancer cells and macrophages. Administration of RFP-tagged exosomes enhanced migration of macrophages and induced macrophage polarization in vitro. In orthotopic TNBC models, noninvasive bioluminescent imaging, ultrasound-guided photoacoustic imaging, and histological analysis revealed that intravenous injection of RFP-tagged exosomes promoted primary tumor growth and axillary LN metastasis in which expression of CD206, a marker or alternatively activated type 2 (M2) macrophages, was significantly higher than expression of NOS2, a marker of classically activated type 1 (M1) macrophages. These results suggest breast cancer cell-derived exosomes stimulate macrophage polarization that creates favorable conditions for LN metastatic processes in TNBC.
Twist-4 distribution amplitudes of the K* and phi mesons in QCD

We present a systematic study of twist-4 light-cone distribution amplitudes of the K* and meson in QCD. The structure of SU(3)-breaking corrections is studied in detail. Non-perturbative input parameters are estimated from QCD sum rules and a renormalon based model. As a by-product, we give a complete reanalysis of the parameters of the twist-4 ρ-meson distribution amplitudes.
Subset of Cortical Layer 6b Neurons Selectively Innervates Higher Order Thalamic Nuclei in Mice

Abstract The thalamus receives input from 3 distinct cortical layers, but input from only 2 of these has been well characterized. We therefore investigated whether the third input, derived from layer 6b, is more similar to the projections from layer 6a or layer 5. We studied the projections of a restricted population of deep layer 6 cells (“layer 6b cells”) taking advantage of the transgenic mouse Tg(Drd1a-cre)FK164Gsat/Mmucd (Drd1a-Cre), that selectively expresses Cre-recombinase in a subpopulation of layer 6b neurons across the entire cortical mantle. At P8, 18% of layer 6b neurons are labeled with Drd1a-Cre::tdTomato in somatosensory cortex (SS), and some co-express known layer 6b markers. Using Cre-dependent viral tracing, we identified topographical projections to higher order thalamic nuclei. VGluT1+ synapses formed by labeled layer 6b projections were found in posterior thalamic nucleus (Po) but not in the (pre)thalamic reticular nucleus (TRN). The lack of TRN collaterals was confirmed with single-cell tracing from SS. Transmission electron microscopy comparison of terminal varicosities from layer 5 and layer 6b axons in Po showed that L6b varicosities are markedly smaller and simpler than the majority from L5. Our results suggest that L6b projections to the thalamus are distinct from both L5 and L6a projections.
Learning by Playing - Solving Sparse Reward Tasks from Scratch

We propose Scheduled Auxiliary Control (SAC-X), a new learning paradigm in the context of Reinforcement Learning (RL). SAC-X enables learning of complex behaviors - from scratch - in the presence of multiple sparse reward signals. To this end, the agent is equipped with a set of general auxiliary tasks, that it attempts to learn simultaneously via off-policy RL. The key idea behind our method is that active (learned) scheduling and execution of auxiliary policies allows the agent to efficiently explore its environment - enabling it to excel at sparse reward RL. Our experiments in several challenging robotic manipulation settings demonstrate the power of our approach.
Effects of hyper- and hypothyroidism on the development and proliferation of testicular cells in prepubertal rats.

Thyroid hormones are important in the development and regulation of testes. This study was conducted to determine the effects of hyper- and hypothyroidism on testicular development in prepubertal rats aged 20-70 days. Weaning male rats (20 days old) until day 70 age were randomly divided into four groups: control, hyperthyroid (hyper-T), hypothyroid (hypo-T) and hypothyroid treated with thyroxine (T4) (hypo-T+T4). The results indicated that thyroid hormones caused a significant effect in body and testis weights, and food and water consumption. In addition there were changes in serum concentrations of tri-iodothyronine, T4, thyroid stimulating hormone (TSH) and testosterone. Histomorphology showed a significant decrease in seminiferous tubule diameter in hyper-T compared to the other groups. Leydig cell numbers showed a significant elevation in hyper-T but not in hypo-T groups. Immunostaining indicated that TSH receptor (TSHR), thyroid hormone receptors α/β (TRαβ) and proliferating cell nuclear antigen (PCNA) have the roles in testicular development. Our findings suggest that hyper- and hypo-thyroidism regulate testicular cell proliferation and spermatogenesis in prepubertal rats, indicating that expression of TSHR, TRαβ and PCNA may be regulated by thyroid hormones that are involved in testicular development; and that the administration of T4 to the hypo-T+T4 group leads to an improvement in the testicular condition.
Paraquat in Developing Countries

Abstract The herbicide, paraquat is considered safe by industry and the bulk of regulators worldwide. However, determinants of exposure from 30 years ago persist in developing countries. Little is known about systemic absorption from occupational exposures. The relationships between exposure determinants, levels of external exposure, biomarkers of exposure, and outcomes are not clear. High rates of severe acute poisonings have been documented. In addition, topical injuries occur in as many as 50% of exposed workers. Non-worker populations are also at risk, particularly children. Long-term and delayed health effects include Parkinson's disease, lung effects, and skin cancer. Regulatory agencies have not fully recognized either the inherent toxicity of paraquat or the particular risks derived from exposures in developing countries. Independent risk assessment in the developing; country context and application of the precautionary principle are necessary to prevent adverse effects of dangerous pesticides in susceptible populations.
Pattern Discrimination Using Feedforward Networks: A Benchmark Study of Scaling Behavior

The discrimination powers of multilayer perceptron (MLP) and learning vector quantization (LVQ) networks are compared for overlapping gaussian distributions. It is shown, both analytically and with Monte Carlo studies, that the MLP network handles high-dimensional problems in a more efficient way than LVQ. This is mainly due to the sigmoidal form of the MLP transfer function, but also to the fact that the MLP uses hyperplanes more efficiently. Both algorithms are equally robust to limited training sets and the learning curves fall off like 1/M, where M is the training set size, which is compared to theoretical predictions from statistical estimates and Vapnik-Chervonenkis bounds.
Use of multiple‐locus variable‐number of tandem repeats analysis (MLVA) to investigate genetic diversity of Salmonella enterica subsp. enterica serovar Typhimurium isolates from human, food, and veterinary sources

Salmonella enterica subspecies enterica serovar Typhimurium is the most common zoonotic pathogen in Bulgaria. To allow efficient outbreak investigations and surveillance in the food chain, accurate and discriminatory methods for typing are needed. This study evaluated the use of multiple‐locus variable‐number of tandem repeats analysis (MLVA) and compared results with antimicrobial resistance (AMR) determinations for 100 S. Typhimurium strains isolated in Bulgaria during 2008–2012 (50 veterinary/food and 50 human isolates). Results showed that isolates were divided into 80 and 34 groups using MLVA and AMR, respectively. Simpson's index of diversity was determined to 0.994 ± 0.003 and 0.945 ± 0.012. The most frequently encountered MLVA profiles were 3‐11‐9‐NA‐211 (n = 5); 3‐12‐9‐NA‐211 (n = 3); 3‐12‐11‐21‐311 (n = 3); 3‐17‐10‐NA‐311 (n = 3); 2‐20‐9‐7‐212 (n = 3); and 2‐23‐NA‐NA‐111 (n = 3). No clustering of isolates related to susceptibility/resistance to antimicrobials, source of isolation, or year of isolation was observed. Some MLVA types were found in both human and veterinary/food isolates, indicating a possible route of transmission. A majority (83%) of the isolates were found to be resistant against at least one antimicrobial and 44% against ≥4 antimicrobials. Further studies are needed to verify MLVA usefulness over a longer period of time and with more isolates, including outbreak strains.
A phase I/II randomized trial of clofarabine or fludarabine added to idarubicin and cytarabine for adults with relapsed or refractory acute myeloid leukemia

Abstract The purine nucleoside analogues clofarabine and fludarabine are active in acute myeloid leukemia (AML). We conducted a phase I/II randomized study of idarubicin and cytarabine with either clofarabine (CIA) or fludarabine (FIA) for relapsed or refractory AML. Clofarabine 15 mg/m2 was identified as the recommended phase II dose. Eighty-one patients were assigned using adaptive randomization to CIA (n = 48) or FIA (n = 33). The complete response (CR)/CR without platelet recovery rate did not differ between CIA and FIA (38% versus 30%, respectively; p = .50). In both arms, more than half of patients who had received only one prior line of therapy achieved remission. The median event-free survival for CIA and FIA was 2.0 and 1.9 months (p = .48), and the median overall survival was 6.3 and 4.7 months, respectively (p = .28). No significant differences in adverse events or early mortality rates were observed. Overall, CIA and FIA resulted in similar response rates and survival in patients with relapsed/refractory AML.