Miracle-dz/UniFAR-FTUs huggingface dataset:
A four‐tiered transcriptional regulatory circuit controls flagellar biogenesis in Pseudomonas aeruginosa

The single polar flagellum of Pseudomonas aeruginosa is an important virulence and colonization factor of this opportunistic pathogen. In this study, the annotation of the genes belonging to the fla regulon was updated and their organization was analysed in strains PAK and PAO1, representative type‐a and type‐b strains of P. aeruginosa respectively. The flagellar genes are clustered in three non‐contiguous regions of the chromosome. A polymorphic locus flanked by flgJ and fleQ in Region I contains a glycosylation island in PAK. The expression and ordered assembly of the complex multicomponent flagellum is intricately regulated. Dedicated flagellar genes fleQ, fleS, fleR, fliA, flgM and fleN encode proteins that participate in the regulation of the flagellar transcriptional circuit. In addition, expression of the flagellum is coordinately regulated with other P. aeruginosa virulence factors by the alternative sigma factor σ54, encoded by rpoN. In order to gain insight into the hierarchical regulation of flagellar genes, deletion mutations were constructed in fleQ, fleR, fliA and rpoN. The transcriptional impact of these mutations was examined by transcriptional profiling using a P. aeruginosa whole genome microarray. Analysis of the transcriptomes generated for each of these mutants indicates a four‐tiered (Classes I‐IV) hierarchy of transcriptional regulation. Class I genes are constitutively expressed and include the transcriptional regulator fleQ and the alternative sigma factor fliA (σ28). Class II genes including fleSR, encoding a two‐component regulatory system require FleQ and RpoN (σ54) for their transcriptional activation. Class III genes are positively regulated by the activated response regulator FleR in concert with RpoN. The transcription of Class IV genes is dependent on the availability of free FliA following the export of the FliA specific antisigma factor FlgM through the basal body rod‐hook structure (assembled from Class II and III gene products). Two previously uncharacterized genes, which are coordinately regulated with known flagellar genes have been identified by genome‐wide analysis and their role in flagellar biogenesis was analysed.
Functional Network Mirrored in the Prefrontal Cortex, Caudate Nucleus, and Thalamus: High-Resolution Functional Imaging and Structural Connectivity

Despite myriads of studies on a parallel organization of cortico-striatal-thalamo-cortical loops, direct evidence of this has been lacking for the healthy human brain. Here, we scrutinize the functional specificity of the cortico-subcortical loops depending on varying levels of cognitive hierarchy as well as their structural connectivity with high-resolution fMRI and diffusion-weighted MRI (dMRI) at 7 tesla. Three levels of cognitive hierarchy were implemented in two domains: second language and nonlanguage. In fMRI, for the higher level, activations were found in the ventroanterior portion of the prefrontal cortex (PFC), the head of the caudate nucleus (CN), and the ventral anterior nucleus (VA) in the thalamus. Conversely, for the lower level, activations were located in the posterior region of the PFC, the body of the CN, and the medial dorsal nucleus (MD) in the thalamus. This gradient pattern of activations was furthermore shown to be tenable by the parallel connectivity in dMRI tractography connecting the anterior regions of the PFC with the head of the CN and the VA in the thalamus, whereas the posterior activations of the PFC were linked to the body of the CN and the MD in the thalamus. This is the first human in vivo study combining fMRI and dMRI showing that the functional specificity is mirrored within the cortico-subcortical loop substantiated by parallel networks.
Progress in the understanding and treatment of chronic anal fissure

BACKGROUND Chronic anal fissure is a common and painful condition associated with internal anal sphincter hypertonia. Reduction of this hypertonia improves the local blood supply, encouraging fissure healing. Surgical sphincterotomy is very successful at healing these fissures but requires an operation with associated morbidity. Temporary reduction in sphincter tone can be achieved on an outpatient basis by applying a topical nitric oxide donor (for example, glyceryl trinitrate) or injecting botulinum toxin into the anal sphincter. METHODS A Medline database was used to perform a literature search for articles relating to the non-surgical treatment of chronic anal fissure. RESULTS Review of the literature shows botulinum toxin injection to be more effective at healing chronic anal fissures than topical glyceryl trinitrate. Topical isosorbide dinitrate has not been directly compared with either of these two agents but has a healing rate approaching that of botulinum toxin injection. The main side effect of botulinum toxin injection is temporary faecal incontinence in approximately 2% of cases, whereas topical nitrates cause headaches in 20%–100% of cases. No long term side effects were identified with any of the medical treatments. CONCLUSION Chemical sphincterotomy is an effective treatment for chronic anal fissure and has the advantages over surgical treatment of avoiding long term complications (notably incontinence) and not requiring hospitalisation.
The effect of haemostatic agents on early healing of the extraction socket.

AIM This study aims to explore the effect of two commercially available haemostatic agents (i.e., collagen sponge and oxide cellulose) on early healing of the extraction socket. MATERIAL AND METHODS In a murine model, bilateral maxillary first molars were extracted and the sockets were filled with or without haemostatic agents. Histology, histomorphometry and immunostaining assays were performed on samples harvested on postextraction day 1, 3, 7 and 14. In vitro studies were also designed to investigate the effect of agents on the dynamics of pH and viability of cells. RESULTS Early socket healing was delayed by both agents but with different patterns. The migration of cells was impeded by oxide cellulose on postextraction day 1 compared with the collagen and the control group. The proliferation and osteogenic differentiation of cells were delayed by both materials. Moreover, apoptosis of periodontal ligament cells was present in the haemostatic agent groups. These effects are attributed to the compression to periodontal ligament by both agents, the acidic niche caused by oxide cellulose, and the intense foreign body reaction and inflammatory response caused by the agents. CONCLUSIONS The placement of haemostatic agents delay the early extraction socket healing via different biological mechanism.
Research Priorities in Limb and Task-Specific Dystonias

Dystonia, which causes intermittent or sustained abnormal postures and movements, can present in a focal or a generalized manner. In the limbs, focal dystonia can occur in either the upper or lower limbs and may be task-specific causing abnormal motor performance for only a specific task, such as in writer’s cramp, runner’s dystonia, or musician’s dystonia. Focal limb dystonia can be non-task-specific and may, in some circumstances, be associated with parkinsonian disorders. The true prevalence of focal limb dystonia is not known and is likely currently underestimated, leaving a knowledge gap and an opportunity for future research. The pathophysiology of focal limb dystonia shares some commonalities with other dystonias with a loss of inhibition in the central nervous system and a loss of the normal regulation of plasticity, called homeostatic plasticity. Functional imaging studies revealed abnormalities in several anatomical networks that involve the cortex, basal ganglia, and cerebellum. Further studies should focus on distinguishing cause from effect in both physiology and imaging studies to permit focus on most relevant biological correlates of dystonia. There is no specific therapy for the treatment of limb dystonia given the variability in presentation, but off-label botulinum toxin therapy is often applied to focal limb and task-specific dystonia. Various rehabilitation techniques have been applied and rehabilitation interventions may improve outcomes, but small sample size and lack of direct comparisons between methods to evaluate comparative efficacy limit conclusions. Finally, non-invasive and invasive therapeutic modalities have been explored in small studies with design limitations that do not yet clearly provide direction for larger clinical trials that could support new clinical therapies. Given these gaps in our clinical, pathophysiologic, and therapeutic knowledge, we have identified priorities for future research including: the development of diagnostic criteria for limb dystonia, more precise phenotypic characterization and innovative clinical trial design that considers clinical heterogeneity, and limited available number of participants.
STIS spectroscopy of newborn massive stars in SMC N81

Using Hubble Space Telescope observations with STIS, we study the main exciting stars of N81, a high excitation compact H II region in the Small Magellanic Cloud (SMC). These far UV observations are the first spectroscopic measurements of stars in such a region and reveal features characteristic of an O6-O8 stellar type. The astonishing weakness of their wind profiles and their sub-luminosity (up to ∼2 mag fainter in M V than the corresponding dwarfs) make these stars a unique stellar population in the Magellanic Clouds. Our analysis suggests that they are probably in the Hertzsprung-Russell diagram locus of a particularly young class of massive stars, the so-called Vz luminosity class, as they are arriving at the zero age main sequence.
Stimulation Selectivity of the “Thin-Film Longitudinal Intrafascicular Electrode” (tfLIFE) and the “Transverse Intrafascicular Multi-Channel Electrode” (TIME) in the Large Nerve Animal Model

Neural prostheses are limited by the availability of peripheral neural electrodes to record the user's intention or provide sensory feedback through functional electrical stimulation. Our objective was to compare the ability of the novel “transverse intrafascicular multi-channel electrode” (TIME) and an earlier generation “thin-film longitudinal intrafascicular electrode” (tfLIFE) to selectively stimulate nerve fascicles and activate forelimb muscles in pigs. TIME was designed to access a larger subpopulation of fascicles than tfLIFE and should therefore be able to selectively activate a larger number of muscles. Electrodes were implanted in the median nerve, and sequential electric stimulation was applied to individual contacts. The compound muscle action potentials of seven muscles were recorded to quantify muscle recruitment. As expected, TIME was able to recruit more muscles with higher selectivity than tfLIFE (significant difference when comparing the performance of an entire electrode); a similar activation current was used (no significant difference). Histological analysis revealed that electrodes were located between fascicles, which influenced the selectivity and activation current level. In conclusion, TIME is a viable neural interface for selective activation of multiple fascicles in human-sized nerves that may assist to pave the way for future neuroprosthesis applications.
Epidemiology and clinical consequences of drug-resistant tuberculosis in a Guatemalan hospital.

STUDY OBJECTIVE To determine the epidemiology and clinical consequences of drug-resistant TB in Guatemala. DESIGN A prospective study conducted for 12 months. SETTING A thoracic referral hospital in western Guatemala. PATIENTS Three hundred and seventy-six patients with confirmed TB. RESULTS Of 376 confirmed cases, 335 (89%) were culture-positive. Tests of drug sensitivities to four first-line antituberculous drugs were performed in 172 (51%) of the culture-positive cases. Fifty-one patients (30%) were resistant to at least one antimicrobial agent, and 26 (15%) were resistant to at least two drugs. In a multivariate model of clinically available patient characteristics, only cavitary disease (odds ratio=2.1; 95% confidence interval, 1.1-6.6) and a history of taking anti-TB medication for >2 weeks (OR=3.0; 95% CI, 1.5-10.3) were independent predictors of resistance to two or more anti-TB agents. Resistance to two or more anti-TB drugs was the single independent predictor of treatment failure (OR=6.4; 95% CI, 2.3-17.8). Twenty-four of 172 patients (14%) who denied having received prior anti-TB therapy were infected with resistant organisms, suggesting ongoing transmission of drug-resistant strains. Although 84% (69 of 82 cases) of patients with fully susceptible organisms and 89% (17 of 19 cases) with singly resistant organisms were cured, only 45% of patients (10 of 22 cases) infected with organisms resistant to two or more agents were successfully treated. CONCLUSIONS At this sentinel site for complicated TB, a substantial subset of cases who are infected with drug-resistant bacteria cannot be easily identified or treated.
Automatic extrinsic calibration for lidar-stereo vehicle sensor setups

Sensor setups consisting of a combination of 3D range scanner lasers and stereo vision systems are becoming a popular choice for on-board perception systems in vehicles; however, the combined use of both sources of information implies a tedious calibration process. We present a method for extrinsic calibration of lidar-stereo camera pairs without user intervention. Our calibration approach is aimed to cope with the constraints commonly found in automotive setups, such as low-resolution and specific sensor poses. To demonstrate the performance of our method, we also introduce a novel approach for the quantitative assessment of the calibration results, based on a simulation environment. Tests using real devices have been conducted as well, proving the usability of the system and the improvement over the existing approaches. Code is available at http://wiki.ros. org/velo2cam_calibration.
A Markov-Chain Monte Carlo Approach to Simultaneous Localization and Mapping

A Markov-chain Monte Carlo based algorithm is provided to solve the Simultaneous localization and mapping (SLAM) problem with general dynamics and observation model under open-loop control and provided that the map-representation is finite dimensional. To our knowledge this is the first provably consistent yet (close-to) practical solution to this problem. The superiority of our algorithm over alternative SLAM algorithms is demonstrated in a difficult loop closing situation.
Not All Kinds of Revegetation Are Created Equal: Revegetation Type Influences Bird Assemblages in Threatened Australian Woodland Ecosystems

The value for biodiversity of large intact areas of native vegetation is well established. The biodiversity value of regrowth vegetation is also increasingly recognised worldwide. However, there can be different kinds of revegetation that have different origins. Are there differences in the richness and composition of biotic communities in different kinds of revegetation? The answer remains unknown or poorly known in many ecosystems. We examined the conservation value of different kinds of revegetation through a comparative study of birds in 193 sites surveyed over ten years in four growth types located in semi-cleared agricultural areas of south-eastern Australia. These growth types were resprout regrowth, seedling regrowth, plantings, and old growth. Our investigation produced several key findings: (1) Marked differences in the bird assemblages of plantings, resprout regrowth, seedling regrowth, and old growth. (2) Differences in the number of species detected significantly more often in the different growth types; 29 species for plantings, 25 for seedling regrowth, 20 for resprout regrowth, and 15 for old growth. (3) Many bird species of conservation concern were significantly more often recorded in resprout regrowth, seedling regrowth or plantings but no species of conservation concern were recorded most often in old growth. We suggest that differences in bird occurrence among different growth types are likely to be strongly associated with growth-type differences in stand structural complexity. Our findings suggest a range of vegetation growth types are likely to be required in a given farmland area to support the diverse array of bird species that have the potential to occur in Australian temperate woodland ecosystems. Our results also highlight the inherent conservation value of regrowth woodland and suggest that current policies which allow it to be cleared or thinned need to be carefully re-examined.
N-3 polyunsaturated fatty acids and allergic disease

Purpose of reviewWith escalating rates of allergic disease, it is vital to explore novel causal pathways. This review examines the evidence for a potential role of changing dietary intake of ω-3 polyunsaturated fatty acids in the development, treatment and prevention of allergic diseases. Recent findingsAlthough it is difficult to determine the contribution of altered (decreased) dietary intake of ω-3 polyunsaturated fatty acids to the recent rise in the incidence of allergic disease, there is growing evidence that these nutrients have antiinflammatory properties and may modulate immune responses. These fatty acids have few side effects, and may be of some benefit in established allergic diseases (such as asthma and atopic dermatitis), although these effects are not strong. Because of this limited efficacy in established disease, the focus has shifted to the potential benefits of these immune modulators in earlier life for disease prevention. Two recent preliminary reports in infants suggest that dietary ω-3 polyunsaturated fatty acid supplements in pregnancy or in the early postnatal period could have immunomodulatory properties and associated clinical effects, although more studies are now needed. Novel synthetic polyunsaturated fatty acids with more potent and selective antiinflammatory effects may also provide safe therapeutic and preventive strategies in the future. SummaryDietary factors are important but still under-explored candidates in the search for environmental strategies to reduce the enormous impact of allergic diseases in modernized societies. There is an ongoing need for further research into the role of ω-3 polyunsaturated fatty acids in allergic disease, particularly in early life before atopy is established.
Off-target effects of BCR–ABL1 inhibitors and their potential long-term implications in patients with chronic myeloid leukemia

Abstract In patients with chronic myeloid leukemia (CML), use of the BCR–ABL1-specific tyrosine kinase inhibitors (TKIs) imatinib, nilotinib and dasatinib has greatly improved patient survival and prolonged disease remission. More than 10 years of data from imatinib clinical studies and many years of data for nilotinib and dasatinib have demonstrated that these TKIs are well tolerated in most patients with CML. However, these inhibitors are not entirely BCR–ABL1-specific, and this lack of specificity could account for the off-target effects of these drugs. Adverse events (AEs) are off-target effects that are detrimental to the patient. The underlying mechanisms that contribute to these effects are poorly understood and the long-term consequences of chronic TKI therapy remain largely unknown, particularly with the newer agents. Here, we review the preclinical and clinical data for several of the more frequent AEs associated with TKIs and discuss the therapeutic relevance of these AEs for patients with CML.
Effect of acupuncture compared with placebo-acupuncture at P6 as additional antiemetic prophylaxis in high-dose chemotherapy and autologous peripheral blood stem cell transplantation: a randomized controlled single-blind trial.

PURPOSE The purpose is to investigate an additional antiemetic effect to ondansetron with needle acupuncture at P6 compared with nonskin-penetrating placebo acupuncture in patients undergoing high-dose chemotherapy and autologous peripheral blood stem cell transplantation. EXPERIMENTAL DESIGN Eighty patients who were admitted to hospital for high-dose chemotherapy and autologous peripheral blood stem cell transplantation were included into a randomized placebo-controlled single-blind trial. The patients were randomized to receive acupuncture (n = 41) or noninvasive placebo acupuncture (n = 39) at the acupuncture point P6 30 min before first application of high-dose chemotherapy and the day after. All patients received 8 mg ondansetron/day i.v. as basic antiemetic prophylaxis. The main outcome measure was the rate of patients who either had at least one episode of vomiting or required any additional antiemetic drugs on the first 2 days of chemotherapy. RESULTS The main outcome measure showed no significant difference (P = 0.82): 61% failure in the acupuncture group and 64% in the placebo acupuncture group (95% confidence interval of 3% difference: -18.1 and 24.3%). Comparing nausea, episodes of vomiting or retching and number of additionally required antiemetic drugs did not provide any discrepancy with the main result. CONCLUSIONS This study suggests that in combination with ondansetron i.v. , invasive needle acupuncture at P6 compared with nonskin-penetrating placebo acupuncture has no additional effect for the prevention of acute nausea and vomiting in high-dose chemotherapy.
Analysis of some exactly solvable diminishing urn models

We study several exactly solvable Purn models with a diminishing character, namely, balls of a specified color, say x are completely drawn after a finite number of draws. The main quantity of interest here is the number of balls left when balls of color x are completely removed. We consider several diminishing urns studied previously in the literature such as the pills problem, the cannibal urns and the OK Corral problem, and derive exact and limiting distributions. Our approach is based on solving recurrences via generating functions and partial differential equations.
Use of medical consultants for hospitalized surgical patients: an observational cohort study.

IMPORTANCE Payments around episodes of inpatient surgery vary widely among hospitals. As payers move toward bundled payments, understanding sources of variation, including use of medical consultants, is important. OBJECTIVE To describe the use of medical consultations for hospitalized surgical patients, factors associated with use, and practice variation across hospitals. DESIGN, SETTING, AND PARTICIPANTS Observational retrospective cohort study of fee-for-service Medicare patients undergoing colectomy or total hip replacement (THR) between January 1, 2007, and December 31, 2010, at US acute care hospitals. MAIN OUTCOMES AND MEASURES Number of inpatient medical consultations. RESULTS More than half of patients undergoing colectomy (91,684) or THR (339,319) received at least 1 medical consultation while hospitalized (69% and 63%, respectively). Median consultant visits from a medicine physician were 9 (interquartile range [IQR], 4-19) for colectomy and 3 for THR (IQR, 2-5). The likelihood of having at least 1 medical consultation varied widely among hospitals (interquartile range [IQR], 50%-91% for colectomy and 36%-90% for THR). For colectomy, settings associated with greater use included nonteaching (adjusted risk ratio [ARR], 1.14 [95% CI, 1.04-1.26]) and for-profit (ARR, 1.10 [95% CI, 1.01-1.20]). Variation in use of medical consultations was greater for colectomy patients without complications (IQR, 47%-79%) compared with those with complications (IQR, 90%-95%). Results stratified by complications were similar for THR. CONCLUSIONS AND RELEVANCE The use of medical consultations varied widely across hospitals, particularly for surgical patients without complications. Understanding the value of medical consultations will be important as hospitals prepare for bundled payments and strive to enhance efficiency.