Miracle-dz/UniFAR-FTUs huggingface dataset:
Beyond similarity assessment: selecting the optimal model for sequence alignment via the Factorized Asymptotic Bayesian algorithm

Abstract Motivation Pair Hidden Markov Models (PHMMs) are probabilistic models used for pairwise sequence alignment, a quintessential problem in bioinformatics. PHMMs include three types of hidden states: match, insertion and deletion. Most previous studies have used one or two hidden states for each PHMM state type. However, few studies have examined the number of states suitable for representing sequence data or improving alignment accuracy. Results We developed a novel method to select superior models (including the number of hidden states) for PHMM. Our method selects models with the highest posterior probability using Factorized Information Criterion, which is widely utilized in model selection for probabilistic models with hidden variables. Our simulations indicated that this method has excellent model selection capabilities with slightly improved alignment accuracy. We applied our method to DNA datasets from 5 and 28 species, ultimately selecting more complex models than those used in previous studies. Availability and implementation The software is available at https://github.com/bigsea-t/fab-phmm. Supplementary information Supplementary data are available at Bioinformatics online.
Icariin ameliorates dexamethasone-induced bone deterioration in an experimental mouse model via activation of microRNA-186 inhibition of cathepsin K

The present study aimed to investigate bone deterioration in glucocorticoid-induced osteoporosis (GIOP) mice, and the anti-osteoporosis effect and underlying molecular mechanism of icariin. Dexamethasone (DSM) treatment was demonstrated to facilitate the induction of hypercalciuria in GIOP mice. Icariin treatment reversed the dexamethasone (DXM)-induced disequilibrium of calcium homeostasis and bone resorption, and increased serum alkaline phosphatase, tartrate resistant acid phosphatase, osteocalcin and deoxypyridinoline. Haematoxylin and eosin staining revealed an increase in disconnections and separation in the trabecular bone network of the tibial proximal metaphysis, in the GIOP group. Icariin treatment reversed the DXM-induced trabecular deleterious effects, and stimulated bone remodeling in GIOP mice. Furthermore, the results demonstrated that the mRNA and protein expression of cathepsin K were significantly increased in GIOP mice, compared with the control group. Icariin treatment may suppress the expression of cathepsin K in the tibia of GIOP mice. The levels of microRNA (miR)-186 were markedly reduced in the tibia of GIOP mice compared with control group; however, this was inhibited by icariin treatment. Bioinformatics analysis demonstrated that miR-186 regulates cathepsin K via binding to the upstream 3′-untranslated region. Furthermore, transfection with miR-186 mimics resulted in inhibition of cathepsin K expression, whereas miR-186 inhibitors facilitated cathepsin K expression in osteoclasts. In conclusion, the present study demonstrated the protective effects of icariin against bone deteriorations in the experimental GIOP mice, and the underlying mechanism was mediated, at least partially, via activation of miR-186-mediated suppression of cathepsin K. These results provide evidence to support the use of icariin as a therapeutic approach in the management of glucocorticoid-induced bone loss, and the disequilibrium of calcium homeostasis.
Implementation of rapid diagnostics with antimicrobial stewardship

ABSTRACT Introduction: Antimicrobial stewardship (ASP) is an intervention-based program to improve patient outcomes to infection while limiting spread of resistance and unintended consequences. Many rapid diagnostic tools are now FDA cleared for clinical use, with three evaluated across multiple settings: Matrix Assisted Laser Desorption Ionization Time-of-Flight Mass Spectrometry, Verigene, and FilmArray. Areas covered: This review will focus on studies published that evaluated ASP intervention with rapid diagnostic implementation on outcomes of infection. A description of the key ASP personnel, rapid diagnostic notification methods, hours of notification, and scope of ASP intervention is summarized. Expert commentary: It is critical that ASPs continually re-evaluate and evolve with technological advances. Rapid diagnostic tools are powerful in their ability to identify organisms quickly. A trained clinician is needed to evaluate the results and interact with the providers to educate them on result interpretation and optimal antimicrobial selection to maximize treatment success.
A Novel Polyamide 12 Polymerization System and its Use for a LCM-process to Produce CFRP

The aim of this study was to investigate the scope of the recently developed polymerization molding system for polyamide 12 (PA12), especially with respect to the formation of carbon fiber-reinforced PA12 composites. Initial screening of PA12 composite formation was performed by means of an internal mixer in order to identify the suitable type of surface-treated carbon fiber (CF). The content of residual lauryllactam (LL) monomer reflected the influence of the CF-treatment on the polymerization molding involving anionic in situ polymerization of LL. The cryogenic fracture surfaces were analysed by scanning electron microscopy (SEM) in order to evaluate the adhesion quality between the components. Finally, a bench-scale polymerization molding process was established successfully for the fabrication of multi-axial laminates. Macromechanical tests and dynamic mechanical thermo-analysis (DMTA) indicated that the performance of the new polymerization molding process is very similar to that of state-of-the-art PA12/CF composites.
Transplant recipients are vulnerable to coverage denial under Medicare Part D

Transplant immunosuppressants are often used off‐label because of insufficient randomized prospective trial data to achieve organ‐specific US Food and Drug Administration (FDA) approval. Transplant recipients who rely on Medicare Part D for immunosuppressant drug coverage are vulnerable to coverage denial for off‐label prescriptions, unless use is supported by Centers for Medicare & Medicaid Services (CMS)–approved compendia. An integrated dataset including national transplant registry data and 3 years of dispensed pharmacy records was used to identify the prevalence of immunosuppression use that is both off‐label and not supported by CMS‐approved compendia. Numbers of potentially vulnerable transplant recipients were identified. Off‐label and off‐compendia immunosuppression regimens are frequently prescribed (3‐year mean: lung 66.5%, intestine 34.2%, pancreas 33.4%, heart 21.8%, liver 16.5%, kidney 0%). The annual retail cost of these at‐risk medications exceeds $30 million. This population‐based study of transplant immunosuppressants vulnerable to claim denials under Medicare Part D coverage demonstrates a substantial gap between clinical practice, current FDA approval processes, and policy mandates for pharmaceutical coverage. This coverage barrier reduces access to life‐saving medications for patients without alternative resources and may increase the risk of graft loss and death from medication nonadherence.
A numerical study of swage autofrettage

This paper describes a numerical analysis of the swaging autofrettage of a gun barrel by forcing an oversize mandrel (or swage ) through the barrel. Analyses are conducted on a two pass swaging procedure in which two separate swages are driven through the barrel. Differences between the maximum swage force required and the resulting barrel deformations and stresses that result from single and two pass swaging are discussed. The effects of changes to swage geometry for single pass swaging are also considered.
Durability of GFRP Rebars in Simulated Concrete Solutions under Accelerated Aging Conditions

This paper discusses the potential ingress and effects of simulated concrete pore solution species on glass fiber-reinforced polymer (GFRP) rebars. Knowing that diffusion of moisture into the fiber-matrix interphase in a composite could cause fiber-matrix debonding and that the presence of alkalis at the location of the glass surface would lead to fiber degradation, particular attention was devoted to investigating whether GFRP rebars allow both species to penetrate or allow only water, while blocking the alkalis. To investigate this scenario, GFRP rebars were immersed in five types of simulated concrete pore solutions at elevated temperatures. Penetration of alkalis was assessed using X-ray mapping of backscattered electron images (BEI) and crosschecked by line and point energy dispersive spectroscopy (EDS) techniques. The effects of diffusion at the fiber-matrix interphase were observed by investigating the degradation of constituents at the interphase. Degradation of polymer matrix was assessed by a Fourier transform infrared (FTIR) spectroscopy. Degradation of fiber was investigated by observing highly magnified scanning electron microscopy (SEM) images and point EDS analyses close to the interphase. Debonding of fibers from the matrix was investigated using a SEM technique. Fiber-matrix debonding took place in a few samples, despite the fact that the glass fibers and polymer matrix remained essentially intact and that no penetration of alkalis into the GFRP rebars was observed. This debonding, which occurred only for samples exposed to 75°C, is believed to be caused by hydrolysis of fiber sizing at high temperatures. Finally, this study shows that the vinyl ester (VE) polymer matrix used acts as an effective semipermeable membrane by allowing the penetration of water, while blocking alkali ions.
Effectiveness of influenza vaccine in the elderly.

OBJECTIVE Each year, influenza and its complications account for 10,000-40,000 excess deaths in the United States. Over 80% of these deaths occur among the elderly. The Advisory Committee on Immunization Practices for the US Public Health Service and others recommend that all persons 65 years of age and older as well as other persons with high-risk conditions receive annual influenza vaccination. Despite these recommendations, 40% or more of high-risk persons fail to receive influenza vaccine. Among the barriers to successful immunization efforts are persistent uncertainties regarding the effectiveness of the vaccine in preventing morbidity and mortality associated with influenza. The purpose of this study was to assess influenza vaccine effectiveness in reducing hospitalization rates for a broad range of influenza-associated complications, in reducing deaths from all causes, and in reducing hospitalization costs among all elderly enrollees of a large health maintenance organization. METHODS A serial cohort study with internal controls was designed. All enrollees, 65 years of age and older, were identified for each of three consecutive vaccination and subsequent influenza seasons for 1990-1991 through 1992-1993. Baseline characteristics and outcome data were collected from computerized, linked, administrative data bases. Outcomes were adjusted for the presence of baseline characteristics including age, gender, high-risk diagnoses, medication refills in high-risk therapeutic classes, and previous health care resource utilization. RESULTS There were more than 25,000 seniors in each of the three study cohorts. Influenza vaccination rates ranged from 45 to 58%, and vaccinated subjects at baseline appeared to be 'sicker' than nonvaccinated subjects. Influenza vaccination was associated with significant reductions in all outcomes evaluated including outpatient visits (17% reduction in pneumonia and influenza visits, 6.4% reduction in all respiratory condition visits), hospitalizations (51.2% reduction in pneumonia and influenza hospitalizations, 32.5% reduction in all respiratory condition hospitalizations, 28.6% reduction in congestive heart failure hospitalizations), hospitalization costs (30.7% reduction in hospitalization costs for all respiratory conditions and congestive heart failure combined), and deaths from all causes (45% reduction in death from all causes). CONCLUSIONS Influenza vaccination of elderly persons living in the community is associated with reduced hospitalizations from complications from influenza, with fewer deaths during the influenza season, and with direct health care cost savings. Few, if any, other preventive or therapeutic interventions for adults match or exceed these benefits.
Inhibition of the MEK/ERK pathway augments nab-paclitaxel-based chemotherapy effects in preclinical models of pancreatic cancer

Nab-paclitaxel (NPT) combination with gemcitabine (Gem) represents the standard chemotherapy for pancreatic ductal adenocarcinoma (PDAC). Genetic alterations of the RAS/RAF/MEK/ERK (MAPK) signaling pathway yielding constitutive activation of the ERK cascade have been implicated as drivers of PDAC. Inhibition of downstream targets in the RAS-MAPK cascade such as MEK remains a promising therapeutic strategy. The efficacy of trametinib (Tra), a small molecule inhibitor of MEK1/2 kinase activity, in combination with nab-paclitaxel-based chemotherapy was evaluated in preclinical models of PDAC. The addition of trametinib to chemotherapy regimens showed a trend for an additive effect on tumor growth inhibition in subcutaneous AsPC-1 and Panc-1 PDAC xenografts. In a peritoneal dissemination model, median animal survival compared to controls (20 days) was increased after therapy with NPT (33 days, a 65% increase), Tra (31 days, a 55% increase), NPT+Tra (37 days, a 85% increase), NPT+Gem (39 days, a 95% increase) and NPT+Gem+Tra (49 days, a 145% increase). Effects of therapy on intratumoral proliferation and apoptosis corresponded with tumor growth inhibition. Trametinib effects were specifically accompanied by a decrease in phospho-ERK and an increase in cleaved caspase-3 and cleaved PARP-1 proteins. These findings suggest that the effects of nab-paclitaxel-based chemotherapy can be enhanced through specific inhibition of MEK1/2 kinase activity, and supports the clinical application of trametinib in combination with standard nab-paclitaxel-based chemotherapy in PDAC patients.
Does Gender Influence Participation?

Purpose The purpose of the study was to determine the effects of gender on participation in a community-based, culturally tailored diabetes lifestyle intervention, led by trained community health workers (CHW) and conducted with African Americans and Latinos with type 2 diabetes. Methods This study utilized data collected from 180 participants. Multivariable binary and cumulative logistic regression models were used to analyze associations between gender and race/ethnicity with study completion and participation in 3 aspects of the intervention: group classes, CHW home visits, and CHW-accompanied doctor visits. Results Among Latinos, men were less likely than women to complete the study, attend group classes, and complete CHW home visits. There were no gender differences in participation seen among African Americans. Conclusions Diabetes management interventions may need to adapt their designs to optimize retention and participation of Latino men. Among African American men, the CHW model may be promising. Reasons for low participation among Latino men should receive more study. Future studies should assess whether similar findings apply in other communities and populations.
Effects of Kaolin Clay Particle Film on Southern Highbush (Vaccinium corymbosumL.) Blueberry Plants

Abstract Two separate studies were conducted to study the effects of kaolin applications (Surround WP) on southern highbush blueberries (Vaccinium corymbosumL.). When applied to mature blueberry plants, kaolin clay emulsion dried to form a white reflective film and affected bud development, fruit set and development, plant growth, and fruit yield, but had no effect on fruit quality attributes. ‘Cooper’ received a single application of kaolin during flowering (bud stages 3-6) which increased fruit set and reduced the rate of flower bud development. Berry size was reduced with kaolin, perhaps due to increased number of fruit present. ‘Magnolia’ received a single application of kaolin at four different stages of maturity resulting in a linear increase in plant volume with early applications. When kaolin was applied before fruit set, yield was increased with no significant residue left on the fruit.
Fungal peritonitis in patients on peritoneal dialysis.

Fungal peritonitis (FP) is a serious complication of peritoneal dialysis, both in terms of morbidity and mortality. Available data on the effectiveness of fluconazole in eradicating FP without catheter removal are still controversial. We reviewed 20 FP cases that occurred among 325 patients who underwent peritoneal dialysis in our center between January 1984 and January 1992, in order to establish whether a profile of patients at risk of developing FP could be identified and to evaluate the effectiveness of fluconazole in treating FP (7 cases). Age, sex, a particular cause of end-stage renal disease, and the presence of diabetes did not correlate significantly with the development of FP. The risk of FP increased in patients on immunosuppressive treatment. Sixteen of our 20 patients had bacterial peritonitis during the month before they developed FP. Nineteen were treated with antibiotics. Neither the type of bacterial organism isolated during the bacterial peritonitis preceding FP nor modality and duration of antibiotic treatment correlated significantly with the development of FP. Patients who subsequently developed FP were more frequently treated with antibiotics while in hospital (p < 0.001). Candida species accounted for 15 of our 20 FP cases (75%), with Candida albicans being by far the most common isolate. Treatment strategies varied among the 20 patients. The combination of intravenous or intraperitoneal administration of 5-fluorocytosine and oral administration of fluconazole was used in 7 cases: only 1 patient was cured without catheter removal, 1 patient died within the first 4 days of treatment, removal of peritoneal catheter was necessary in the other 5 patients. (ABSTRACT TRUNCATED AT 250 WORDS)
Radiologically isolated syndrome or subclinical multiple sclerosis: MAGNIMS consensus recommendations

The widespread use of brain magnetic resonance imaging (MRI) has greatly increased findings of unanticipated asymptomatic intracranial abnormalities of uncertain clinical significance. These incidental findings on brain MRI are of various nature and origin and only rarely include abnormalities that could be interpreted as inflammatory or demyelinating lesions(1). However, the increase of unexpected MRI alterations has overall augmented the awareness for findings that have the morphology, size, location and distribution highly suggestive of a demyelinating disease. This has led to the definition of "radiologically isolated syndrome" (RIS), which was recently introduced to describe those asymptomatic subjects with brain MRI abnormalities suggestive of multiple sclerosis (MS) and lacking historical accounts of prior demyelinating events or an identifiable better reason for the observed changes(2). Since its first description, RIS has been widely debated and the risk of RIS evolving into MS has been investigated. According to existing data, a number of RIS subjects evolve to MS over time, demonstrating that RIS, at least in some cases, represents a preclinical stage of MS. RIS, however, is an entity that still needs to be better defined, with a number of issues needing to be addressed. These include the lack of expert guidelines on the management of RIS subjects and criteria that can establish the extent to which MRI lesions fulfilling the RIS criteria in asymptomatic subjects may represent subclinical MS or may be related to abnormalities that are not related to MS. We provide here expert recommendations that can help distinguish between subjects with low risk of developing MS and those that can be diagnosed with subclinical MS. Suggestions for the management of subjects stratified by risk for a future demyelinating event will also be provided. A summary of the main proposed recommendations is given in Table 1.
Optimized Self-Localization for SLAM in Dynamic Scenes Using Probability Hypothesis Density Filters

In many applications, sensors that map the positions of objects in unknown environments are installed on dynamic platforms. As measurements are relative to the observer's sensors, scene mapping requires accurate knowledge of the observer state. However, in practice, observer reports are subject to positioning errors. Simultaneous localization and mapping addresses the joint estimation problem of observer localization and scene mapping. State-of-the-art approaches typically use visual or optical sensors and therefore rely on static beacons in the environment to anchor the observer estimate. However, many applications involving sensors that are not conventionally used for Simultaneous Localization and Mapping (SLAM) are affected by highly dynamic scenes, such that the static world assumption is invalid. This paper proposes a novel approach for dynamic scenes, called GEneralized Motion (GEM) SLAM. Based on probability hypothesis density filters, the proposed approach probabilistically anchors the observer state by fusing observer information inferred from the scene with reports of the observer motion. This paper derives the general, theoretical framework for GEM-SLAM, and shows that it generalizes existing Probability Hypothesis Density (PHD)-based SLAM algorithms. Simulations for a model-specific realization using range-bearing sensors and multiple moving objects highlight that GEM-SLAM achieves significant improvements over three benchmark algorithms.
Direct pituitary effects of estrogen and progesterone on gonadotropin secretion in the ovariectomized ewe.

The direct pituitary effects of estrogen and progesterone on the secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were studied in ovariectomized (OVX) ewes in which the pituitary had been disconnected surgically from the hypothalamus (hypothalamo-pituitary disconnection, HPD). Gonadotropin secretion was restored with hourly pulses of 500 ng gonadotropin-releasing hormone (GnRH) via intra-atrial cannulae. Intramuscular injections of 50 micrograms estradiol benzoate (EB) to 5 sheep initially caused reductions (approximately 50%) in plasma LH baseline, peak values and LH pulse amplitude. Thereafter all parameters of plasma LH concentration increased 2- to 3-fold above starting values. After these 5 sheep had received 2 subcutaneous progesterone implants (mean +/- SEM plasma levels 5.3 +/- 1.5 nmol/l), the biphasic LH response to EB was still apparent and increases in LH peak values (267 +/- 19%) and LH pulse amplitudes (262 +/- 23%) were greater (p less than 0.05) than those seen with EB alone (195 +/- 11 and 172 +/- 14%, respectively). The presence of 2 progesterone implants alone did not change plasma LH baseline, peak values or pulse amplitude, or plasma FSH values. In the second experiment, where 4 OVX-HPD ewes were given 4 progesterone implants (plasma progesterone 27.7 +/- 3.4 nmol/l), there were no effects on basal plasma LH or plasma FSH values. The LH responses to EB were more marked in 4 OVX-HPD ewes given 4 progesterone implants than in the animals given EB alone. Also, the estrogen-induced LH surge occurred earlier in the ewes given 4 progesterone implants than in those given estrogen alone. (ABSTRACT TRUNCATED AT 250 WORDS)