Miracle-dz/UniFAR-FTUs huggingface dataset:
A formal methods approach to interpretable reinforcement learning for robotic planning

A formal methods approach to reinforcement learning generates rewards from a formal language and guarantees safety. Growing interest in reinforcement learning approaches to robotic planning and control raises concerns of predictability and safety of robot behaviors realized solely through learned control policies. In addition, formally defining reward functions for complex tasks is challenging, and faulty rewards are prone to exploitation by the learning agent. Here, we propose a formal methods approach to reinforcement learning that (i) provides a formal specification language that integrates high-level, rich, task specifications with a priori, domain-specific knowledge; (ii) makes the reward generation process easily interpretable; (iii) guides the policy generation process according to the specification; and (iv) guarantees the satisfaction of the (critical) safety component of the specification. The main ingredients of our computational framework are a predicate temporal logic specifically tailored for robotic tasks and an automaton-guided, safe reinforcement learning algorithm based on control barrier functions. Although the proposed framework is quite general, we motivate it and illustrate it experimentally for a robotic cooking task, in which two manipulators worked together to make hot dogs.
The impact of posterior epidural adipose tissue on postoperative outcomes after posterior decompression surgery for lumbar spinal stenosis: A prospectively randomized non-inferiority trial

Study design: The present study is a prospectively randomized study. Objective: The objective of the study was to evaluate the impact of posterior epidural adipose tissue (PAT) on postoperative outcome following lumbar decompression surgery for lumbar spinal stenosis (LSS) by whether PAT was removed or preserved during the surgical procedure. Summary of background data: In posterior decompression surgery for LSS, PAT is routinely removed without knowledge of its role and significance. However, considering adipose tissue has regenerative properties of damaged neighboring tissues or itself, PAT, which is adipose tissue located at peridural space, might also have a potential to regenerate the neighboring damaged tissue, including dura and nerve root in the lumbar spine, but this has not been thoroughly studied. Methods: Of the 185 eligible patients screened for the current study, 181 patients were enrolled and randomly allocated into either group A (PAT removal, n = 90) or group B (PAT retention, n = 91). The primary outcome measure was pain intensity on the lower back and lower extremity. The secondary outcome measures were functional outcome based on the Oswestry disability index (ODI) and walking distance, complications during the surgical procedure, and surgical outcomes. Results: Postoperative pain intensity on the lower back and lower extremity was greater in group A than in group B. Functional status on ODI and walking distance was also worse in group B than in group A (64.9% in group A and 66.2% in group B). The number of patients with aggravated pain intensity and deteriorated functional status in postoperative follow-up times was significantly greater in group A than in group B. There were no significant differences in surgical outcome and complications between the groups. Conclusion: Preserving epidural fat may be favorable in postoperative outcomes of posterior decompression surgery for LSS compared to removing epidural fat.
Retraction: SDR9C7 Promotes Lymph Node Metastases in Patients with Esophageal Squamous Cell Carcinoma

The corresponding author has stated that there were unintentional errors in image selection and placement, and that this did not affect the cell counts and statistical analyses or the final conclusions of the study. The authors provided the underlying dataset for the invasion, migration and MTT assays shown in Figs 3 and 4, as well as the underlying image files for Figs 3A, 4E, and 4G, and replicate images captured during the original experiments. Replacement images were provided for the incorrect panels; however, the corresponding author indicated that records were not kept relating to the cell types, conditions, and experimental design associated with the image files. Additional concerns were raised regarding the reporting of the microarray experiment. The corresponding author indicated that experiments and data analysis related to Fig 1 were performed by an external company, which was not stated in the published article. The complete microarray data set was not initially made available. The authors have deposited the
PHLDA1 Does Not Contribute Directly to Heat Shock-Induced Apoptosis of Spermatocytes

Spermatocytes are among the most heat-sensitive cells and the exposure of testes to heat shock results in their Heat Shock Factor 1 (HSF1)-mediated apoptosis. Several lines of evidence suggest that pleckstrin-homology-like domain family A, member 1 (PHLDA1) plays a role in promoting heat shock-induced cell death in spermatogenic cells, yet its precise physiological role is not well understood. Aiming to elucidate the hypothetical role of PHLDA1 in HSF1-mediated apoptosis of spermatogenic cells we characterized its expression in mouse testes during normal development and after heat shock. We stated that transcription of Phlda1 is upregulated by heat shock in many adult mouse organs including the testes. Analyzes of the Phlda1 expression during postnatal development indicate that it is expressed in pre-meiotic or somatic cells of the testis. It starts to be transcribed much earlier than spermatocytes are fully developed and its transcripts and protein products do not accumulate further in the later stages. Moreover, neither heat shock nor expression of constitutively active HSF1 results in the accumulation of PHLDA1 protein in meiotic and post-meiotic cells although both conditions induce massive apoptosis of spermatocytes. Furthermore, the overexpression of PHLDA1 in NIH3T3 cells leads to cell detachment, yet classical apoptosis is not observed. Therefore, our findings indicate that PHLDA1 cannot directly contribute to the heat-induced apoptosis of spermatocytes. Instead, PHLDA1 could hypothetically participate in death of spermatocytes indirectly via activation of changes in the somatic or pre-meiotic cells present in the testes.
Complete Chloroplast Genome of Paphiopedilum delenatii and Phylogenetic Relationships among Orchidaceae

Paphiopedilum delenatii is a native orchid of Vietnam with highly attractive floral traits. Unfortunately, it is now listed as a critically endangered species with a few hundred individuals remaining in nature. In this study, we performed next-generation sequencing of P. delenatii and assembled its complete chloroplast genome. The whole chloroplast genome of P. delenatii was 160,955 bp in size, 35.6% of which was GC content, and exhibited typical quadripartite structure of plastid genomes with four distinct regions, including the large and small single-copy regions and a pair of inverted repeat regions. There were, in total, 130 genes annotated in the genome: 77 coding genes, 39 tRNA genes, 8 rRNA genes, and 6 pseudogenes. The loss of ndh genes and variation in inverted repeat (IR) boundaries as well as data of simple sequence repeats (SSRs) and divergent hotspots provided useful information for identification applications and phylogenetic studies of Paphiopedilum species. Whole chloroplast genomes could be used as an effective super barcode for species identification or for developing other identification markers, which subsequently serves the conservation of Paphiopedilum species.
Pharmacist–Physician Collaboration to Improve the Accuracy of Medication Information in Electronic Medical Discharge Summaries: Effectiveness and Sustainability

Inaccurate or missing medication information in medical discharge summaries is a widespread and intractable problem. This study evaluated the effectiveness and sustainability of an intervention in which ward-based hospital pharmacists reviewed, contributed and verified medication information in electronic discharge summaries (EDSs) in collaboration with physicians. Retrospective audits of randomly selected EDSs were conducted on seven wards at a major public hospital before and after implementation of the intervention and repeated two years later on four wards where the intervention was incorporated into usual pharmacist care. EDSs for 265 patients (prescribed a median of nine discharge medications) were assessed across the three time points. Pharmacists verified the EDSs for 47% patients in the first post-intervention audit and 68% patients in the second post-intervention audit. Following the intervention, the proportion of patients with one or more clinically significant discharge medication list discrepancy fell from 40/93 (43%) to 14/92 (15%), p < 0.001. The proportion of clinically significant medication changes stated in the EDSs increased from 222/417 (53%) to 296/366 (81%), p < 0.001, and the proportion both stated and explained increased from 206/417 (49%) to 245/366 (67%), p < 0.001. Significant improvements were still evident after two years. Pharmacists spent a median of 5 (range 2–16) minutes per patient contributing to EDSs. Logistics, timing and pharmacist workload were barriers to delivering the intervention. Additional staff resources is needed to enable pharmacists to consistently deliver this effective intervention.
An Optofluidic Tweeze-and-Drag Cell Stretcher in a Microfluidic Channel

We report an optofluidic tweeze-and-drag cell stretcher in a microfluidic channel. We distinguish healthy and glutaraldehyde-treated rabbit red blood cells based on their different mechanical deformations at a cell-stretching throughput of ~1.2 cells/s. © 2019 The Author(s)
Melatonin Promotes Uterine and Placental Health: Potential Molecular Mechanisms

The development of the endometrium is a cyclic event tightly regulated by hormones and growth factors to coordinate the menstrual cycle while promoting a suitable microenvironment for embryo implantation during the “receptivity window”. Many women experience uterine failures that hamper the success of conception, such as endometrium thickness, endometriosis, luteal phase defects, endometrial polyps, adenomyosis, viral infection, and even endometrial cancer; most of these disturbances involve changes in endocrine components or cell damage. The emerging evidence has proven that circadian rhythm deregulation followed by low circulating melatonin is associated with low implantation rates and difficulties to maintain pregnancy. Given that melatonin is a circadian-regulating hormone also involved in the maintenance of uterine homeostasis through regulation of numerous pathways associated with uterine receptivity and gestation, the success of female reproduction may be dependent on the levels and activity of uterine and placental melatonin. Based on the fact that irregular production of maternal and placental melatonin is related to recurrent spontaneous abortion and maternal/fetal disturbances, melatonin replacement may offer an excellent opportunity to restore normal physiological function of the affected tissues. By alleviating oxidative damage in the placenta, melatonin favors nutrient transfer and improves vascular dynamics at the uterine–placental interface. This review focuses on the main in vivo and in vitro functions of melatonin on uterine physiological processes, such as decidualization and implantation, and also on the feto-maternal tissues, and reviews how exogenous melatonin functions from a mechanistic standpoint to preserve the organ health. New insights on the potential signaling pathways whereby melatonin resists preeclampsia and endometriosis are further emphasized in this review.
Lipid Systems for the Delivery of Amphotericin B in Antifungal Therapy

Amphotericin B (AmB), a broad-spectrum polyene antibiotic in the clinic for more than fifty years, remains the gold standard in the treatment of life-threatening invasive fungal infections and visceral leishmaniasis. Due to its poor water solubility and membrane permeability, AmB is conventionally formulated with deoxycholate as a micellar suspension for intravenous administration, but severe infusion-related side effects and nephrotoxicity hamper its therapeutic potential. Lipid-based formulations, such as liposomal AmB, have been developed which significantly reduce the toxic side effects of the drug. However, their high cost and the need for parenteral administration limit their widespread use. Therefore, delivery systems that can retain or even enhance antimicrobial efficacy while simultaneously reducing AmB adverse events are an active area of research. Among those, lipid systems have been extensively investigated due to the high affinity of AmB for binding lipids. The development of a safe and cost-effective oral formulation able to improve drug accessibility would be a major breakthrough, and several lipid systems for the oral delivery of AmB are currently under development. This review summarizes recent advances in lipid-based systems for targeted delivery of AmB focusing on non-parenteral nanoparticulate formulations mainly investigated over the last five years and highlighting those that are currently in clinical trials.
Differences in Simulated Refractive Outcomes of Photorefractive Keratectomy (PRK) and Laser In-Situ Keratomileusis (LASIK) for Myopia in Same-Eye Virtual Trials

The use of computational mechanics for assessing the structural and optical consequences of corneal refractive procedures is increasing. In practice, surgeons who elect to perform PRK rather than LASIK must often reduce the programmed refractive treatment magnitude to avoid overcorrection of myopia. Building on a recent clinical validation study of finite element analysis (FEA)-based predictions of LASIK outcomes, this study compares predicted responses in the validated LASIK cases to theoretical PRK treatments for the same refractive error. Simulations in 20 eyes demonstrated that PRK resulted in a mean overcorrection of 0.17 ± 0.10 D relative to LASIK and that the magnitude of overcorrection increased as a function of attempted correction. This difference in correction closely matched (within 0.06 ± 0.03 D) observed differences in PRK and LASIK from a historical nomogram incorporating thousands of cases. The surgically induced corneal strain was higher in LASIK than PRK and resulted in more forward displacement of the central stroma and, consequently, less relative flattening in LASIK. This FE model provides structural confirmation of a mechanism of action for the difference in refractive outcomes of these two keratorefractive techniques, and the results were in agreement with empirical clinical data.
Bisphenol a Exposure, DNA Methylation, and Asthma in Children

Epidemiological studies have reported the relationship between bisphenol A (BPA) exposure and increased prevalence of asthma, but the mechanisms remain unclear. Here, we investigated whether BPA exposure and DNA methylation related to asthma in children. We collected urinary and blood samples from 228 children (Childhood Environment and Allergic Diseases Study cohort) aged 3 years. Thirty-three candidate genes potentially interacting with BPA exposure were selected from a toxicogenomics database. DNA methylation was measured in 22 blood samples with top-high and bottom-low exposures of BPA. Candidate genes with differential methylation levels were validated by qPCR and promoter associated CpG islands have been investigated. Correlations between the methylation percentage and BPA exposure and asthma were analyzed. According to our findings, MAPK1 showed differential methylation and was further investigated in 228 children. Adjusting for confounders, urinary BPA glucuronide (BPAG) level inversely correlated with MAPK1 promoter methylation (β = −0.539, p = 0.010). For the logistic regression analysis, MAPK1 methylation status was dichotomized into higher methylated and lower methylated groups with cut off continuous variable of median of promoter methylation percentage (50%) while performing the analysis. MAPK1 methylation was lower in children with asthma than in children without asthma (mean ± SD; 69.82 ± 5.88% vs. 79.82 ± 5.56%) (p = 0.001). Mediation analysis suggested that MAPK1 methylation acts as a mediation variable between BPA exposure and asthma. The mechanism of BPA exposure on childhood asthma might, therefore, be through the alteration of MAPK1 methylation. The mechanism of BPA exposure on childhood asthma might, therefore, be through the alteration of MAPK1 methylation.
Determinants of Sedentary Behaviour in Individuals with COPD: A Qualitative Exploration Guided by the Theoretical Domains Framework

Abstract In people with chronic obstructive pulmonary disease (COPD), there is increasing recognition that the prolonged accumulation of sedentary time (ST) is associated with adverse cardio-metabolic health outcomes. Nevertheless, changing this lifestyle, which has evolved over several decades, is likely to be challenging. This study reports the determinants, perceived by individuals with COPD, as being important for reducing ST. An in-depth understanding of this information is essential when planning an intervention to reduce ST. Fourteen individuals with COPD completed semi-structured one-on-one interviews, which were audio recorded and transcribed verbatim. Both the interview schedule and mapping of data items extracted from the interview transcripts were informed by the Theoretical Domains Framework (TDF). A total of 867 quotes were mapped to the 14 TDF domains. Seven of the fourteen domains were identified as being important determinants for reducing ST: knowledge, beliefs about consequences, beliefs about capabilities, environmental context and resources, social influences, social/professional role and identity, and behavioural regulation. There was a lack of knowledge regarding the meaning of sedentary behaviour. Participants’ desire to be educated by knowledgeable health professionals in a formal programme was a dominant theme across multiple domains. The most frequently reported barriers to reducing ST related to the domains of social/professional role and identity and environmental context and resources, while the most frequently reported enablers were related to the domains pertaining to beliefs about consequences and social influences. Potential strategies to reduce ST among people with COPD include education and other determinants identified in this research.
Interference-Aware Radio Resource Management for Cognitive High-Throughput Satellite Systems

By providing interactive broadband services to geographical areas underserved by terrestrial infrastructure, multi-beam satellite systems play a central role in future wireless communications. Targeting the terabit throughput requirements in satellite communications, we introduce a cognitive radio-based high-throughput satellite (HTS) system architecture where full frequency reuse is employed among beams. Moreover, by analyzing the characteristics of the considered architecture, we discuss the design challenges of radio resource management in cognitive HTS systems exposed to both intra-system and inter-system co-channel interference. Furthermore, to combat interference with low overhead, we propose a generic interference-aware resource management framework based on joint spatial division and multiplexing (JSDM). Under this framework, user grouping along with two-stage precoding is studied to achieve substantial improvement in the overall system throughput. Finally, some future research directions and challenges are also given.
Intrinsic Disorder-Based Design of Stable Globular Proteins

Directed stabilization of globular proteins via substitution of a minimal number of amino acid residues is one of the most complicated experimental tasks. This work summarizes our research on the effect of amino acid substitutions on the protein stability utilizing the outputs of the analysis of intrinsic disorder predisposition of target proteins. This allowed us to formulate the basis of one of the possible approaches to the stabilization of globular proteins. The idea is quite simple. To stabilize a protein as a whole, one needs to find its "weakest spot" and stabilize it, but the question is how this weak spot can be found in a query protein. Our approach is based on the utilization of the computational tools for the per-residue evaluation of intrinsic disorder predisposition to search for the "weakest spot" of a query protein (i.e., the region(s) with the highest local predisposition for intrinsic disorder). When such "weakest spot" is found, it can be stabilized through a limited number of point mutations by introducing order-promoting residues at hot spots, thereby increasing structural stability of a protein as a whole. Using this approach, we were able to obtain stable mutant forms of several globular proteins, such as Gαo, GFP, ribosome protein L1, and circular permutant of apical domain of GroEL.
Occurrence of Thermophilic Microorganisms in Different Full Scale Biogas Plants

Background: In recent years, various substrates have been tested to increase the sustainable production of biomethane. The effect of these substrates on methanogenesis has been investigated mainly in small volume fermenters and were, for the most part, focused on studying the diversity of mesophilic microorganisms. However, studies of thermophilic communities in large scale operating mesophilic biogas plants do not yet exist. Methods: Microbiological, biochemical, biophysical methods, and statistical analysis were used to track thermophilic communities in mesophilic anaerobic digesters. Results: The diversity of the main thermophile genera in eight biogas plants located in the Czech Republic using different input substrates was investigated. In total, 19 thermophilic genera were detected after 16S rRNA gene sequencing. The highest percentage (40.8%) of thermophiles was found in the Modřice biogas plant where the input substrate was primary sludge and biological sludge (50/50, w/w %). The smallest percentage (1.87%) of thermophiles was found in the Čejč biogas plant with the input substrate being maize silage and liquid pig manure (80/20, w/w %). Conclusions: The composition of the anaerobic consortia in anaerobic digesters is an important factor for the biogas plant operator. The present study can help characterizing the impact of input feeds on the composition of microbial communities in these plants.
Extraintestinal Clostridioides difficile Infections: Epidemiology in a University Hospital in Hungary and Review of the Literature

Extraintestinal manifestations of Clostridioides difficile infections (CDIs) are very uncommon, and according to the literature, poor outcomes and a high mortality have been observed among affected individuals. The objective of this study was to investigate the incidence rate of extraintestinal infections caused by C. difficile (ECD) in a tertiary-care university hospital in Hungary. During a 10-year study period, the microbiology laboratory isolated 4129 individual strains of C. difficile; among these, the majority were either from diarrheal fecal samples or from colonic material and only n = 24 (0.58%) were from extraintestinal sources. The 24 extraintestinal C. difficile isolates were recovered from 22 patients (female-to-male ratio: 1, average age: 55.4 years). The isolates in n = 8 patients were obtained from abdominal infections, e.g., appendicitis, rectal abscess or Crohn’s disease. These extraintestinal cases occurred without concomitant diarrhea. In all, but two cases C. difficile was obtained as a part of a polymicrobial flora. Our isolates were frequently toxigenic and mostly belonged to PCR ribotype 027. Resistance to metronidazole, vancomycin, clindamycin and rifampin were 0%, 0%, 20.5% and 9.7%, respectively. The increasing amount of reports of C. difficile extraintestinal infections should be noted, as these infections are characterized by a poor outcome and high mortality rate.