Miracle-dz/UniFAR-FTUs huggingface dataset:
Epidemiology of DYT1 dystonia

Objective To estimate the prevalence of TOR1A sequence variants associated with DYT1 dystonia. Methods We determined the frequency of the common trinucleotide deletion that causes DYT1 in the Genome Aggregation Database and the Penn Medicine Biobank, totaling exomes from over 135,000 individuals. We also evaluated the prevalence of other possible pathogenic variants in this gene and asked whether the D216H polymorphism is linked to a higher diagnostic rate for dystonia independent of the DYT1-causing mutation. Results The estimated range of prevalence of the most common pathogenic variant that causes DYT1 is ∼17.6–26.1 carriers per 100,000 individuals. Based on the different data sets used, we predict that there are between 54,366 and 80,891 mutation carriers in the United States, which, due to the reduced penetrance of this variant, would translate into 16,475–24,513 DYT1 patients. Conclusions Our data provide a prevalence estimate of the most common DYT1 mutation in the general population. This information is specifically important for those with interest in the development of precision therapeutics for dystonia.
Effects of Fenitrothion and Deltamethrin Insecticides on Certain Biochemical Parameters of Culex pipiens larvae

The efficiency of two insecticides, fenitrothion (Organophosphorus) and deltamethrin (Pyrethroid) against the 3 instar larvae of Culex pipiens were evaluated under the laboratory conditions. LC50 values for fenitrothion and deltamethrin were 0.089 and 0.0016 ppm, respectively. Also, the effect of the tested insecticides on some biochemical parameters was carried out through evaluation the effect of sublethal concentration of the tested compounds on the activity of acetylcholinesterase, aspartate aminotransferase (GOT), alanine aminotransferase (GPT) and protein content after treatment the 3 larval instar for 24 hr. The results indicated that deltamethrin and fenitrothion reduced in the activity of acetylcholinesterase reached to 69.98, 68.0, 73.43 and 65.99% compared to the untreated check with moribund and alive larvae, respectively. As for the transaminases GOT, fenitrothion showed great inhibition on GOT of moribund larvae compared with negligible reduction than the untreated value in alive larvae, showing 97.34 and 16.15% reduction, respectively. On the contrary, deltamethrin caused stimulatory effects on GOT activity in both moribund and alive larvae, reaching 41.15 and 30.21% increase than the normal value, respectively. As for total protein, data clearly showed that both the tested insecticides caused slight alteration in such parameter
Acetonic Fraction of Bidens pilosa Enriched for Maturase K Is Able to Control Cerebral Parasite Burden in Mice Experimentally Infected With Toxoplasma gondii

Toxoplasma gondii infection can cause abortions or congenital infection for a vast number of domestic animals and humans, leading to economic loss in veterinary sciences, as well as severe consequences for immunocompromised patients. Bidens pilosa Linné has been used in ethnopharmacology for treatment of diseases, as malaria, diabetes and hepatitis, in addition to its use as antioxidant, antiallergic, anti-inflammatory, and antiviral. The components of this plant have never been studied before for treatment of toxoplasmosis, and the conventional drugs currently used to treat this disease have high degree of toxicity. Thus, the aim of this study was to evaluate the effect of B. pilosa against T. gondii, by analyzing a total extract of this plant in parallel with a fraction obtained by precipitation in acetone. Also, it was assessed if the acetonic fraction could present lectinic activity, followed by its identification by mass spectrometry. It was observed with the experimental models designed that both total extract and acetonic fraction of B. pilosa were able to control T. gondii infection by in vitro and in vivo experiments, in addition to their low toxicity to host cells. Both total extract and acetonic fraction of this plant display capacity to impair replication of T. gondii tachyzoites. Interesting, the B. pilosa acetonic fraction treatment for 10 days after infection decreases significantly the number of T. gondii brain cyst in comparison with controls. The protein isolated from B. pilosa acetonic fraction was characterized as a novel lectin identified as maturase K. Taken together, these findings open new perspectives to treat patients infected by T. gondii. Future studies will be necessary to investigate the precise mechanism underlying the control of T. gondii infection to impair the replication of this parasite in the host cells after treatment with B. pilosa maturase K.
Impact of Imperfect Disease Detection on the Identification of Risk Factors in Veterinary Epidemiology

Risk factors are key epidemiological concepts that are used to explain disease distributions. Identifying disease risk factors is generally done by comparing the characteristics of diseased and non-diseased populations. However, imperfect disease detectability generates disease observations that do not necessarily represent accurately the true disease situation. In this study, we conducted an extensive simulation exercise to emphasize the impact of imperfect disease detection on the outcomes of logistic models when case reports are aggregated at a larger scale (e.g., diseased animals aggregated at farm level). We used a probabilistic framework to simulate both the disease distribution in herds and imperfect detectability of the infected animals in these herds. These simulations show that, under logistic models, true herd-level risk factors are generally correctly identified but their associated odds ratio are heavily underestimated as soon as the sensitivity of the detection is less than one. If the detectability of infected animals is not only imperfect but also heterogeneous between herds, the variables associated with the detection heterogeneity are likely to be incorrectly identified as risk factors. This probability of type I error increases with increasing heterogeneity of the detectability, and with decreasing sensitivity. Finally, the simulations highlighted that, when count data is available (e.g., number of infected animals in herds), they should not be reduced to a presence/absence dataset at the herd level (e.g., presence or not of at least one infected animal) but rather modeled directly using zero-inflated count models which are shown to be much less sensitive to imperfect detectability issues. In light of these simulations, we revisited the analysis of the French bovine abortion surveillance data, which has already been shown to be characterized by imperfect and heterogeneous abortion detectability. As expected, we found substantial differences between the quantitative outputs of the logistic model and those of the zero-inflated Poisson model. We conclude by strongly recommending that efforts should be made to account for, or at the very least discuss, imperfect disease detectability when assessing associations between putative risk factors and observed disease distributions, and advocate the use of zero-inflated count models if count data is available.
In vitro Interactions of Pseudomonas aeruginosa With Scedosporium Species Frequently Associated With Cystic Fibrosis

Members of the Scedosporium apiospermum species complex are the second most frequently isolated pathogens after Aspergillus fumigatus from cystic fibrosis (CF) patients with fungal pulmonary infections. Even so, the main risk factors for the infection are unrevealed. According to previous studies, bacterial infections might reduce the risk of a fungal infection, but an antibacterial therapy may contribute to the airway colonization by several fungal pathogens. Furthermore, corticosteroids, which are often used to reduce lung inflammation in children and adults with CF, are also proved to enhance the growth of A. fumigatus in vitro. Considering all the above discussed points, we aimed to test how Pseudomonas aeruginosa influences the growth of scedosporia and to investigate the potential effect of commonly applied antibacterial agents and corticosteroids on Scedosporium species. Direct interactions between fungal and bacterial strains were tested using the disk inhibition method. Indirect interactions via volatile compounds were investigated by the plate-in-plate method, while the effect of bacterial media-soluble molecules was tested using a modified cellophane assay and also in liquid culture media conditioned by P. aeruginosa. To test the effect of bacterial signal molecules, antibacterial agents and corticosteroids on the fungal growth, the broth microdilution method was used. We also investigated the germination ability of Scedosporium conidia in the presence of pyocyanin and diffusible signal factor by microscopy. According to our results, P. aeruginosa either inhibited or enhanced the growth of scedosporia depending on the culture conditions and the mode of interactions. When the two pathogens were cultured physically separately from each other in the plate-in-plate tests, the presence of the bacteria was able to stimulate the growth of several fungal isolates. While in direct physical contact, bacterial strains inhibited the fungal growth. This effect might be attributed to bacterial signal molecules, which also proved to inhibit the germination and growth of scedosporia. In addition, antibacterial agents showed growth-promoting, while corticosteroids exhibited growth inhibitory effect on several Scedosporium isolates. These data raise the possibility that a P. aeruginosa infection or a previously administered antibacterial therapy might be able to increase the chance of a Scedosporium colonization in a CF lung.
Selection of Multidrug-Resistant Bacteria in Medicated Animal Feeds

Exposure to antimicrobial resistant (AMR) bacteria is a major public health issue which may, in part, have roots in food production practices that are conducive to the selection of AMR bacteria ultimately impacting the human microbiome through food consumption. Of particular concern is the prophylactic use of antibiotics in animal husbandry, such as the medication of feeds with sulfonamides and other antibiotics not considered clinically relevant, but which may nonetheless co-select for multi-drug resistant (MDR) bacteria harboring resistance to medically important antibiotics. Using a MDR Klebsiella pneumoniae strain exhibiting resistance to sulfonamides and beta-lactams (including carbapenem) as a model, we examined the ability of non-medicated and commercially medicated (sulfonamide) animal feeds to select for the model strain when inoculated at low levels by measuring its recovery along with key AMR markers, sul1(sulfonamide) and blaKPC-3 (meropenem), under different incubation conditions. When non-medicated feeds were supplemented with defined amounts of sulfadiazine the model strain was significantly enriched after incubation in Mueller Hinton Broth at 37°C overnight, or in same at room temperature for a week, with consistent detection of both the sul1 and blaKPC-3 markers as determined by polymerase chain reaction (PCR) techniques to screen colony isolates recovered on plating media. Significant recoveries of the inoculated strain and the sul1 and blaKPC-3 markers were observed with one of three commercially medicated (sulfamethazine) feeds tested under various incubation conditions. These results demonstrate that under certain conditions the prophylactic use of so-called non-priority antibiotics in feeds can potentially lead to co-selection of environmental AMR bacteria with resistance to medically important antibiotics, which may have far-reaching implications for human health.
The association of quality of life between anxiety and depression in patients with chronic rheumatic heart disease

Objective: The main objective of the study was to measure the association of quality of life between anxiety and depression in patients with chronic rheumatic heart disease. Methodology: Psychometric assessment (anxiety and depression) of the subjects was measured using HADS. Clinical data were collected from the Department of Cardiology OPD of Safdarjung Hospital, New Delhi. A total of 500 RHD patients and 100 healthy controls were included in the study based on inclusion and exclusion criteria. Data analysis was performed with Chi square test and ANOVA using IBM SPSS version 22. Findings: Almost 80% of the subjects were suffering from moderate RHD, and 20% were suffering from Severe RHD. Most cases of RHD were suffering from moderate anxiety and depression levels. Among all the variables of SF-36 questionnaire, only pain was only variable associated with anxiety. None of the SF-36 variables was associated with depression in patients with RHD. Conclusion: It was seen that high levels of anxiety and depression levels are present in patients with RHD. It was also observed that the high anxiety levels in the RHD patients can also be a major cause of depression in patients. The factors related to the disease like physical pain, social functioning, and general health causes high anxiety and depression in the patients when the disease prevails over a long time.
An empirical test of the mechanistic underpinnings of interference competition

Interspecific owever, empirical evidence of the resource availability competition is an essential element of the evolution of species and can strongly influence the abundance and distribution of species. Where competition interacts with anthropogenic habitat modification, this natural ecosystem process can become a threatening process. Understanding the mechanisms behind competition in such cases is essential for the formulation of cost-effective management responses for biodiversity conservation. According to the resource availability hypothesis of competition, interference competition limits access to resources by species vulnerable to such aggression and wastes energy in evasive responses. Studying competition is notoriously difficult, however, empirical evidence of the resource availability theory is limited, and there are few published experimental studies showing such an effect at larger scales. We present the results of a controlled and replicated empirical study of interference competition at a landscape scale. We removed an aggressive, overabundant native bird, Manorina melanocephala (noisy miner), whose interference competition is a threatening process for small woodland birds in the highly modified agricultural landscapes of eastern Australia. We monitored foraging and harassment rates of small woodland birds before and after removal to indicate if levels of interference competition changed. Due to unexpected immediate recolonisation, abundance of M. melanocephala in treatment sites declined by only 34% relative to control sites. Twenty-four bird species displayed aggressive behaviour towards other birds and 41 bird species were victims of aggression. Manorina melanocephala was responsible for 66% of all aggressive interactions. After removal, we recorded a doubling in foraging rate of small woodland birds in treatment compared to control sites. This appears to confirm the resource availability hypothesis of competition. Paradoxically, however, increased foraging was not accompanied by a decline in harassment. Low detection rates of harassment of small woodland birds, combined with the modest reduction in abundance of M. melanocephala, make it difficult to draw firm conclusions about the relationship between rates of harassment and rates of foraging.
Volatility estimates increase choice switching and relate to prefrontal activity in schizophrenia

Background Reward-based decision-making is impaired in patients with schizophrenia (PSZ) as reflected by increased choice switching. The underlying cognitive and motivational processes as well as associated neural signatures remain unknown. Reinforcement Learning (RL) and hierarchical Bayesian learning account for choice switching in different ways. We hypothesized that enhanced choice switching, as seen in PSZ during reward-based decision-making, relates to higher-order beliefs about environmental volatility and examined the associated neural activity. Methods 46 medicated PSZ and 43 healthy controls (HC) performed a reward-based decision-making task requiring flexible responses to changing action-outcome contingencies during functional Magnetic Resonance Imaging (fMRI). Detailed computational modeling of choice data was performed, including RL and the hierarchical Gaussian filter (HGF). Trajectories of learning from computational modeling informed the analysis of fMRI data. Results A three-level HGF accounted best for the observed choice data. This model revealed a heightened initial belief about environmental volatility and a stronger influence of volatility on lower-level learning of action-outcome contingencies in PSZ as compared to HC. This was replicated in an independent sample of non-medicated PSZ. Beliefs about environmental volatility were reflected by higher activity in dorsolateral prefrontal cortex of PSZ as compared to HC. Conclusions Our study suggests that PSZ inferred the environment as overly volatile, which may explain increased choice switching. In PSZ, activity in dorsolateral prefrontal cortex was more strongly related to beliefs about environmental volatility. Our computational phenotyping approach may provide useful information to dissect clinical heterogeneity and could improve prediction of outcome.
Microhabitat preference in American bullfrog tadpoles (Lithobates catesbeianus) in relation to predation pressure.

Predation risk is among the key forces driving the evolution of escape behaviours and related phenotypes. Successful avoidance of predators results in increased survival rate and fitness. The behavioural response of individuals under predation pressure has been comparatively well studied, however, most studies focus on specific escape behaviours and not on behavioural plasticity. The American bullfrog (Lithobates catesbeianus) has been an invasive species in the Republic of Korea since the 1970s and has a negative impact on local species. Here, we evaluated the functions of microhabitat preference and behavioural plasticity in L. catesbeianus tadpoles through manipulative experiments. In a first experiment, we placed wildcaught tadpoles with a local predatory fish (Channa argus) into one of three microhabitat treatments: non-vegetated, submerged vegetation, or floating vegetation. The survival rate of tadpoles with submerged vegetation was significantly higher than that in the non-vegetated microhabitat. In contrast, the survival rates of tadpoles with floating vegetation was not significantly different from the two other treatments. In the habitat preference experiment, “unhurt” and “wounded” wildcaught tadpoles were given a choice between the three microhabitat treatments. Both types of tadpoles preferentially selected the submerged vegetation microhabitat compared to the non-vegetated microhabitat. In contrast, only wounded tadpoles significantly preferred floating vegetation over non-vegetated microhabitats. We conclude that L. catesbeianus tadpoles prefer vegetated microhabitats, and especially submerged vegetation. Furthermore, L. catesbeianus tadpoles can adjust their antipredatory behaviour according to previous experience, and thus demonstrate behavioural plasticity by using microhabitats that they do not use in the absence of predators.
Silk fibroin scaffolds: A promising candidate for bone regeneration

It remains a big challenge in clinical practice to repair large-sized bone defects and many factors limit the application of autografts and allografts, The application of exogenous scaffolds is an alternate strategy for bone regeneration, among which the silk fibroin (SF) scaffold is a promising candidate. Due to the advantages of excellent biocompatibility, satisfying mechanical property, controllable biodegradability and structural adjustability, SF scaffolds exhibit great potential in bone regeneration with the help of well-designed structures, bioactive components and functional surface modification. This review will summarize the cell and tissue interaction with SF scaffolds, techniques to fabricate SF-based scaffolds and modifications of SF scaffolds to enhance osteogenesis, which will provide a deep and comprehensive insight into SF scaffolds and inspire the design and fabrication of novel SF scaffolds for superior osteogenic performance. However, there still needs more comprehensive efforts to promote better clinical translation of SF scaffolds, including more experiments in big animal models and clinical trials. Furthermore, deeper investigations are also in demand to reveal the degradation and clearing mechanisms of SF scaffolds and evaluate the influence of degradation products.
Medication adherence, hospitalization, and healthcare resource utilization and costs in patients with pulmonary arterial hypertension treated with endothelin receptor antagonists or phosphodiesterase type-5 inhibitors

Adherence to therapy for pulmonary arterial hypertension is essential to optimize patient outcomes, but data on real-world adherence to different pulmonary arterial hypertension drug classes are limited. This retrospective database analysis evaluated relationships between adherence, hospitalization, and healthcare costs in pulmonary arterial hypertension patients treated with endothelin receptor antagonists or phosphodiesterase type-5 inhibitors. From the IQVIA Adjudicated Health Plan Database, patients with pulmonary arterial hypertension were identified based on diagnostic codes and prescriptions for endothelin receptor antagonists (ambrisentan, bosentan, macitentan) or phosphodiesterase type-5 inhibitors (sildenafil, tadalafil) approved for pulmonary arterial hypertension. Patients were assigned to the class of their most recently initiated (index) pulmonary arterial hypertension therapy between 1 January 2009 and 30 June 2015. Medication adherence was measured by proportion of days covered; patients with proportion of days covered ≥80% were considered adherent. The proportion of adherent patients was higher for endothelin receptor antagonists (571/755; 75.6%) than for phosphodiesterase type-5 inhibitors (970/1578; 61.5%; P < 0.0001). In both groups, hospitalizations declined as proportion of days covered increased. Among adherent patients, those on endothelin receptor antagonists had a significantly lower hospitalization rate than those on phosphodiesterase type-5 inhibitors (23.1% versus 28.5%, P = 0. 0218), fewer hospitalizations (mean (standard deviation) 0.4 (0.8) versus 0.5 (0.9); P = 0.02), and mean hospitalization costs during the six-month post-index ($9510 versus $15,726, P = 0.0318). Increasing adherence reduced hospitalization risk more for endothelin receptor antagonists than for phosphodiesterase type-5 inhibitors (hazard ratio 0.176 versus 0.549, P = 0.001). Rates and numbers of rehospitalizations within 30 days post-discharge were similar between groups. Mean total costs were higher with endothelin receptor antagonists than phosphodiesterase type-5 inhibitors in all patients ($91,328 versus $72,401, P = 0.0003) and in adherent patients ($88,867 versus $56,300, P < 0.0001), driven by higher drug costs.