Miracle-dz/UniFAR-FTUs huggingface dataset:
The MocR‐like transcription factors: pyridoxal 5′‐phosphate‐dependent regulators of bacterial metabolism

Many biological functions played by current proteins were not created by evolution from scratch, rather they were obtained combining already available protein scaffolds. This is the case of MocR‐like bacterial transcription factors (MocR‐TFs), a subclass of GntR transcription regulators, whose structure is the outcome of the fusion between DNA‐binding proteins and pyridoxal 5′‐phosphate (PLP)‐dependent enzymes. The resultant chimeras can count on the properties of both protein classes, i.e. the capability to recognize specific DNA sequences and to bind PLP and amino‐compounds; it is the modulation of such binding properties to confer to MocR‐TFs chimeras the ability to interact with effector molecules and DNA so as to regulate transcription. MocR‐TFs control different metabolic processes involving vitamin B6 and amino acids, which are canonical ligands of PLP‐dependent enzymes. However, MocR‐TFs are also implicated in the metabolism of compounds that are not substrates of PLP‐dependent enzymes, such as rhizopine and ectoine. Genomic analyses show that MocR‐TFs are widespread among eubacteria, implying an essential role in their metabolism and highlighting the scarcity of our knowledge on these important players in microbial metabolism. Although MocR‐TFs have been discovered 15 years ago, the research activity on these transcriptional regulators has only recently intensified, producing a wealth of information that needs to be brought back to general principles. This is the main task of this review, which reports and analyses the available information concerning MocR‐TFs functional role, structural features, interaction with effector molecules and the characteristics of DNA transcriptional factor‐binding sites of MocR‐based regulatory systems.
Active Fixation Control to Predict Saccade Sequences

Visual attention is a field with a considerable history, with eye movement control and prediction forming an important subfield. Fixation modeling in the past decades has been largely dominated computationally by a number of highly influential bottom-up saliency models, such as the Itti-Koch-Niebur model. The accuracy of such models has dramatically increased recently due to deep learning. However, on static images the emphasis of these models has largely been based on non-ordered prediction of fixations through a saliency map. Very few implemented models can generate temporally ordered human-like sequences of saccades beyond an initial fixation point. Towards addressing these shortcomings we present STAR-FC, a novel multi-saccade generator based on the integration of central high-level and object-based saliency and peripheral lower-level feature-based saliency. We have evaluated our model using the CAT2000 database, successfully predicting human patterns of fixation with equivalent accuracy and quality compared to what can be achieved by using one human sequence to predict another.
Homogeneity Without Loss of Generality

We consider higher-order recursion schemes as generators of infinite trees. A sort (simple type) is called homogeneous when all arguments of higher order are taken before any arguments of lower order. We prove that every scheme can be converted into an equivalent one (i.e, generating the same tree) that is homogeneous, that is, uses only homogeneous sorts. Then, we prove the same for safe schemes: every safe scheme can be converted into an equivalent safe homogeneous scheme. Furthermore, we compare two definition of safe schemes: the original definition of Damm, and the modern one. Finally, we prove a lemma which illustrates usefulness of the homogeneity assumption. The results are known, but we prove them in a novel way: by directly manipulating considered schemes. 2012 ACM Subject Classification Theory of computation → Rewrite systems
The Future of Orthopaedic Care: Promoting Psychosocial Resiliency in Orthopaedic Surgical Practices

The biopsychosocial model posits that health is influenced by, and influences, a complex interplay of biological, psychological, and social factors. The emerging focus on integrated health care has emphasized comprehensive assessment and treatment of patients’ biological, psychological, and social needs to promote resiliency (i.e., the ability to “bounce back” in the face of adversity). In parallel, medical care is undergoing a shift in priorities toward awareness of the importance of multidisciplinary treatment that is designed to optimize resiliency and quality of life. Current research indicates that integrated care models improve patient outcomes, are cost-effective, and decrease health-care utilization over time. As practitioners on the front lines treating patients across the continuum of health (e.g., acute injury, self-limiting problems, persistent illness, or aspects of normal human aging), orthopaedic surgeons have a unique opportunity to evolve health-care delivery by spearheading the integration of techniques to address psychosocial factors and promote psychosocial resiliency in orthopaedic practices. Therefore, the goals of this treatise are to contribute to an ongoing conversation in the field, with an emphasis on ways in which psychosocial resiliency can be integrated into routine orthopaedic care. We begin with a review of the role of psychosocial resiliency in orthopaedic conditions and discuss both patient and provider-level barriers to addressing psychosocial factors. We conclude with recommendations for the use of integrated care models and concrete skills that orthopaedic surgeons can use to address and promote psychosocial resiliency in their patients.
Is Ischemic Preconditioning Feasible to Improve Performance at Moderate Altitude?

Our research group has tested ischemic preconditioning (IPC) extensively with the aim of clarifying whether this manipulation is effective in different types of exercise performance tests (1,2). Accordingly, we read with special interest the recent article by Paradis-Deschênes et al. (3) on IPC at simulated altitude. Prior studies of IPC at altitude have been conducted above 3000 m. Accordingly, they (3) sought to examine the ergogenic and physiological effects of IPC at simulated altitudes below 3000 m, specifically, 1200 and 2400 m. Surprisingly, however, the IPCmaneuver was done outside the hypoxic chamber, that is, at sea-level oxygen conditions, whereas the subsequent exercise test was performed inside the altitude chamber 25 min after the IPC application. Ischemic preconditioning could have an early (91 to 2 h) and/or late (912 to 72 h) window of effectiveness on tissue protection (4), but there is no consensus about an ‘‘ideal’’ time window between the last IPC cycle and exercise testing, ranging from 5 to 90 min in most studies (5). Generally, IPC has been shown to improve exercise performance within 90 min of the final cuff inflation in studies for which a beneficial effect has been noted (e.g., 6). Thus, although ParadisDeschênes et al. (3) used a time window (i.e., 25 min) in line with previous observations (5,6), it is implausible to apply IPC at sea level and then be prepared to compete at an altitude of 1200 or 2400 m just 25 min later in a real-world context! Therefore, although the results of Paradis-Deschênes et al. (3) are enticing, in our opinion, the feasibility of IPC as an ergogenic aid for time trial performance at moderate altitude still needs to be appropriately tested. For example, the application of IPC in hypoxic environment might produce deleterious effects given that the IPC itself causes tissue hypoxia during the ischemic period (7). Also, a recent report (8) showed that beneficial effects of IPC at sea level began ‘‘only’’ after 92 h and lasted for at least 8 h in swimmers. Results such as these encourage further investigation into determining how long it might take to transport athletes from sea level to a specific altitude and then whether the ergogenic effects reported for sea level remain at moderate altitude within the same time window.
Prevalence of psychosocial impairment in temporomandibular disorder patients: A systematic review

BACKGROUND Several studies have described high levels of psychosocial disorders in patients with temporomandibular disorders (TMD), but an estimate of their prevalence in populations of TMD patients has never been assessed systematically. OBJECTIVE To conduct a systematic review of the literature on the prevalence of research diagnostic criteria for TMD (RDC/TMD) Axis II findings in TMD patients. METHODS Search for articles was carried out by two independent researchers to retrieve papers published after 1992. Inclusion was reserved to observational studies with a minimum sample size of 100 individuals, which used RDC/TMD diagnostic protocol. Quality assessment was performed with the adoption of the methodological evaluation of observational research (MORE). RESULTS A total of 1186 citations were obtained from search strategy, but only 14 filled the inclusion criteria. Included papers reported somatisation, depression and/or pain-related disability prevalence or scores from populations of 12 different countries. A broad range in the prevalence of moderate-to-severe somatisation in patients with TMD was observed, ranging from 28.5% to 76.6%. Similar results were found for depression, with moderate-to-severe levels in 21.4%-60.1% of patients. Finally, most patients were rated as grade I or II of the Graded Chronic Pain Scale, whereas high pain-related impairment was present in 2.6% to 24% of the individuals. CONCLUSION The prevalence of severe-to-moderate somatisation and depression was high in TMD patients, while severe physical impairment was not commonly reported.
Cachexia in hospitalized patients with heart failure.

AIMS to evaluate cachexia prevalence in hospitalized heart failure (HF) patients by comparing two methods for diagnosing cachexia and alterations in each component involved in its diagnosis. METHOD a cross-sectional study, involving patients diagnosed with HF and admitted between April and August 2015 to a public hospital in the Brazilian Northeast. Cardiac cachexia was defined using the Cachexia Consensus criteria (Washington, DC), which defines cachexia as ≥ 5% unintentional weight loss in the previous 12 months or a body mass index (BMI) ≤ 20.0 kg/m², in combination with at least two of the following criteria: fatigue, anorexia, low hand grip strength, low muscle strength, and biological alterations (hemoglobin < 12 g/dl, albumin < 3.2 g/dl, and PCR ≥ 5 mg/dl), and for comparative purposes a diagnostic criterion which considers weight loss ≥ 6% in at least six months as a cachexia diagnosis. RESULTS one hundred and fifty-six individuals were evaluated, with an average age of 59.1 (± 15.3). Cachexia prevalence was 37.2% and associated with a low BMI (p < 0.001), low muscle mass (p < 0.001), reduced ejection fraction (p = 0.005), hypoalbuminemia (p = 0.040), and anemia (p = 0.002). Among the diagnostic components, the greatest alterations were observed in relation to fatigue (88.2%), anorexia (72.1%) and weight loss (61.7%). CONCLUSIONS the high prevalence of diagnosed cachexia indicates that this condition is common and is associated with poor nutritional state and clinical condition.
Fuzzy Logic Modelling Of The Russian Demographic Space

Demographic processes are extremely difficult to manage and require the different methods of their research. Our studies aimed at modelling the demographic space of Russian regions by using fuzzy clustering. Our analysis is based on the indicators of the regions’ demographic potential. We used our own original methodology combining the statistical procedures of fuzzy clustering and expert survey data. We considered indicators characterizing the reproduction potential and variables characterizing the potential quality of the future population. As a result of fuzzy clustering, five clusters were formed. Our experts evaluated the reproduction potential and the quality of the future population for each cluster. The data for each region were used to calculate their reproduction potential and the quality of their future population. In comparison to hard clustering, fuzzy clustering enhances the flexibility of evaluation: our assesments of each region do not depend exclusively on the potential of the nearest cluster, as we also take into consideration the region’s possible similarities with other neighbouring clusters with different potential. Such modelling allows us to identify those Russian regions that could be considered as ‘growth points’ in the implementation of demographic policy.
The application of laser-ablation microprobe; inductively coupled plasma-mass spectrometry (LAM-ICP-MS) to in situ trace-element determinations in minerals

A laser ablation microprobe (LAM) sample-introduction system, designed for in sira microsampling of minerals in petrographic sections, has been interfacedto anlnductively CoupledPlasma-Mass Spectrometer(ICP-MS). TheLAM consists of aQ-switched Nd:YAG laser with power attenuation and steering optics to guide the laser beam through the phototube of a petrographic microscope, where it is focused onto the petrographic section contained in a sample cell. The response of rock-forming minerals to ablation is related to their absorptivity of the 1064 nm wavelength of the laser beam (a function of the proportion of transifion elements, especially Fe), and their physical properties, particularly cleavage and tenacity. Minerals with a high absolptivity can generally be ablated controllably in thin section. In minerals with low absorptivity, catastrophic ablation may occur due to absorption at interfaces beneath the mineral surface, particularly at the mineral glass slide interface in standard thin sections. Most minerals can be ablated controllably in unsupported polished wafers, grain mounts and polished blocks, where ablation pits with diameten of 2A-40 pm can be achieved routinely. In addition, the ability of the LAM to bore allows production of vertical profiles of element concentrations at a much finer spatial resolution. Comparison of LAMand solution-ICP-MS analyses of titanite, zircon, apatite, uraninite, and garnet separates demonstrates that a simple scheme of calibration employing.a spiked NBS silicate glass reference material, using major-element intemal standards to correct for differences in ablation yield, drift, and matrix effects, provides good accuracy and precision (RSD < 107o, at concentrations > 60 ppm) for a diverse suite of elements. Routine limits of detection are about 0.5 ppm.
A GRASP algorithm based new heuristic for the capacitated location routing problem

Abstract In this paper, the capacitated location-routing problem (CLRP) is studied. CLRP is composed of two hard optimisation problems: the facility location problem and the vehicle routing problem. The objective of CLRP is to determine the best location of multiple depots with their vehicle routes such that the total cost of the solution is minimal. To solve this problem, we propose a greedy randomised adaptive search procedure. The proposed method is based on a new heuristic to construct a feasible CLRP solution, and then a local search-based simulated annealing is used as improvement phase. We have used a new technique to construct the clusters around the depots. To prove the effectiveness of our algorithm, several LRP instances are used. The results found are very encouraging.
FOXA1 levels are decreased in pleural breast cancer metastases after adjuvant endocrine therapy, and this is associated with poor outcome

Estrogen receptor‐alpha (ERα)‐positive breast cancer is often treated with antihormonal regimens. However, resistance to treatment is common, leading to metastatic disease. ERα activity requires the functional involvement of pioneer factors FOXA1 and GATA3, which enable ERα–chromatin binding and are crucial for ERα‐driven cell proliferation. FOXA1 was found increased in metastatic breast cancers in relation to the primary tumor, but a comprehensive clinical assessment thereof, in relation to different metastatic sites and endocrine therapy usage, is currently lacking. Prior cell line‐based reports, however, have revealed that FOXA1 is required for tamoxifen‐resistant tumor cell proliferation. We studied expression levels of ERα, GATA3, and FOXA1 by immunohistochemistry in samples from both primary tumors and various metastatic sites. For all factors, expression levels varied between the metastatic sites. For pleural metastases, strong variation was found in FOXA1 and GATA3 levels. Although GATA3 levels remained unaltered between primary breast cancer and pleural metastases, FOXA1 levels were reduced exclusively in metastases of patients who received endocrine therapies in the adjuvant setting, even though ERα was still expressed. Importantly, decreased FOXA1 levels in pleural metastases correlated with hormone irresponsiveness in the palliative setting, while no such correlation was found for GATA3. With this, we show divergent clinical correlations of the two ERα pioneer factors FOXA1 and GATA3 in metastatic breast cancer, where endocrine therapy resistance was associated with decreased FOXA1 levels in pleural metastases.
Amitriptyline inhibits the MAPK/ERK and CREB pathways and proinflammatory cytokines through A3AR activation in rat neuropathic pain models

Background The pain-relief properties of tricyclic antidepressants can be attributed to several actions. Recent observations suggest that adenosine is involved in the antinociceptive effect of amitriptyline. The A3 adenosine receptor (A3AR) is the only adenosine subtype overexpressed in inflammatory and cancer cells. This study was performed to investigate the role of A3AR in the anti-nociceptive effect of amitriptyline. Methods Spinal nerve-ligated neuropathic pain was induced by ligating the L5 and L6 spinal nerves of male Sprague-Dawley rats. The neuropathic rats were randomly assigned to one of the following three groups (8 per group): a neuropathic pain with normal saline group, a neuropathic pain with amitriptyline group, and a neuropathic pain with amitriptyline and 3-ethyl-5-benzyl- 2-methyl-4-phenylethynyl-6-phenyl-1,4-(±)-dihydropyridine-3,5-dicarboxylate (MRS) group. Amitriptyline or saline was administered intraperitoneally and 3-ethyl-5-benzyl-2-methyl-4-phenylethynyl-6-phenyl-1,4-(±)-dihydropyridine-3,5-dicarboxylate (MRS-1191), an A3AR antagonist, was injected subcutaneously immediately before amitriptyline administration. The level of extracellular signal-regulated kinase P44/42 (ERK1/2), cyclic AMP response element-binding protein (CREB), and proinflammatory cytokines were assessed using immunoblotting or reverse-transciption polymerase chain reaction. Results Amitriptyline increased the mechanical withdrawal threshold of the neuropathic rats. The level of phospho-ERK1/2 and phospho-CREB proteins, and proinflammatory cytokines produced by spinal nerve ligation were significantly reduced by amitriptyline administration. However, the use of MRS-1191 before amitriptyline administration not only reduced the threshold of mechanical allodynia, but also increased the signaling protein and proinflammatory cytokine levels, which were reduced by amitriptyline. Conclusions The results of this study suggest that the anti-nociceptive effect of amitriptyline involves the suppression of ERK1/2 and CREB signaling proteins, and A3AR activation also affects the alleviation of the inflammatory response.
Genotypic Diversity Is Independent of Pathogenicity in Colombian Strains of Cryptococcus neoformans and Cryptococcus gattii in Galleria mellonella

Cryptococcosis is a potentially fatal opportunistic mycosis that affects the lungs and central nervous system. It has been suggested that certain strains of C. neoformans/C. gattii may have the potential to be more virulent according to the molecular type. This study aims to investigate the association between virulence in the G. mellonella model and genotypic diversity of Colombian clinical and environmental isolates of C. neoformans/C. gattii. A total of 33 clinical and 12 environmental isolates were selected according to their geographical origin and sequence types (STs). Pathogenicity was determined using the G. mellonella model, and the cell and capsular size before and after inoculation was determined. For C. neoformans, virulence in G. mellonella revealed that death occurred on average on day 6 (p < 0.05) and that ST5C, 6C, 25C and 71C were the most virulent. In C. gattii, death occurred at 7.3 days (p < 0.05), and ST47C, 58C, 75A and 106C were the most virulent. Capsular size increased for both species after passage in G. mellonella. In conclusion, the pathogenicity of Cryptococcus strains in the G. mellonella invertebrate model is independent of molecular type or pathogenicity factor, even within the same ST, but it is possible to find variable degrees of pathogenicity.
Multi-Band Up-Converted Lasing Behavior in NaYF4:Yb/Er Nanocrystals

Random lasers have attracted great interests and extensively investigation owing to their promising applications. Here, we explored unambiguously the multi-band up-converted random lasing from NaYF4:Yb,Er nanocrystals (NCs). NaYF4:Yb,Er NCs exhibit high effective up-conversion luminescence when they are excited by continuous wave 980 nm laser. We investigated a planar microcavities approach wherein the NaYF4:Yb,Er NCs showed up-converted lasing behavior. The optical pumping of NaYF4:Yb,Er NCs by 980 nm pulsed laser excitation exhibited multi-band lasing. The NaYF4:Yb,Er NCs showed multi-band lasing emission with a line width of 0.2 nm at 540 nm and 0.4 nm at 660 nm. This research promotes potential application in bioimaging and biomedical fields.
Fine structure and classification of shrimp hemocytes

The structure of hemocytes from two species of penaeid shrimp was examined by light and electron (TEM) microscopy. Hemocytes from the two species are indistinguishable and are classified as either agranular, small‐granule, or large‐granule hemocytes. Agranular hemocytes are the smallest of the hemocytes, lack granules, compose only 5–10% of the circulating hemocytes, and are nonrefractile when examined by light microscopy. Small‐granule hemocytes are the most abundant type of hemocyte (75% of all hemocytes), appear nonrefractile, and contain a variable number (1–40) of granules (0.4 μm diameter). Large‐granule hemocytes compose 10–20% of the hemocytes. They are filled with granules (0.8 μm in diameter) that are highly refractile when examined by light microscopy and are electron‐dense when examined by TEM. Our classification scheme is based solely on the absence or presence and relative size of granules. Features used by other researchers, such as cell size, shape, and staining properties, were not used because these features are subtle and/or subjective. The proposed classification is compared with schemes developed for other decapods, and its usefulness and limitations are discussed. This scheme will serve as a basis for further studies on the maturation and physiological function(s) or crustacean hemocytes.