Miracle-dz/UniFAR-FTUs huggingface dataset:
An effective hybrid search mode for multi-objective optimization with constraints

In this paper a new search strategy for multi-objective optimization (MOO) with constraints is proposed based on a hybrid search mode (HSM). The search processes for feasible solutions and optimal solutions are executed in a mixed way for the existing methods. With regard to HSM, a hybrid search mode is proposed, which consists of two processes: Feasibility search mode (FSM) and optimal search mode (OSM). The executions of these two search modes are independent relatively and also adjusted according to the population distribution. In the early stage, FSM plays the leading role for exploring the feasible space since most of the individuals are infeasible. With the increase of the feasible individuals, OSM is the primary operation for the search of optimal individuals. The proposed method is simple to implement and need few extra parameter tuning. The handing method of constraints is tested on several multi-objective optimization problems with constraints. The remarkable results demonstrate its effectiveness and good performance.
Technical Brief: Automatic Classification of Foot Examination Findings Using Clinical Notes and Machine Learning

We examine the feasibility of a machine learning approach to identification of foot examination (FE) findings from the unstructured text of clinical reports. A Support Vector Machine (SVM) based system was constructed to process the text of physical examination sections of in- and out-patient clinical notes to identify if the findings of structural, neurological, and vascular components of a FE revealed normal or abnormal findings or were not assessed. The system was tested on 145 randomly selected patients for each FE component using 10-fold cross validation. The accuracy was 80%, 87% and 88% for structural, neurological, and vascular component classifiers, respectively. Our results indicate that using machine learning to identify FE findings from clinical reports is a viable alternative to manual review and warrants further investigation. This application may improve quality and safety by providing inexpensive and scalable methodology for quality and risk factor assessments at the point of care.
Neuroprotection induced by omega-3 polyunsaturated fatty acids: focus on neuropsychiatric disorders

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A New Technique to Repair Large Bone Defects

It is very difficult to repair large bone defects, especially when they have a complex shape. We have developed a new technique to make a desired copy of rabbit bones. A rabbit distal femur was scanned by computed tomography (CT), and a rectangular-shaped beta-tricalcium phosphate (β-TCP) block with 75% porosity was automatically machined using milling tools into a halfscale copy of the distal femur based on the CT data. The β-TCP block was seeded with bone morphogenetic protein-2 and bone marrow cells obtained from the femur and implanted on the periosteum of the femur. At 10 weeks after implantation, most of the β-TCP block had been replaced by bone and a complete copy of the distal femur was reconstructed. Our findings indicate that this technique will be useful in the clinical setting. We also report the representative clinical results of treatment with β-TCP graft in patients with bone defects since 1989.
Effects of dietary guanidinoacetic acid on growth performance, guanidinoacetic acid absorption and creatine metabolism of lambs

Guanidinoacetic acid (GAA) is the only precursor for the creatine synthesis of vertebrates. Creatine (Cr) and phosphocreatine (PCr) are able to provide energy for the rapid growth and development of the muscle tissue. This study evaluated the effects of dietary different levels GAA on growth performance, GAA absorption and creatine metabolism of lambs. Twenty-four 3-month-old healthy Kazakh male lambs (body weight = 27.35± 0.58 kg) were randomly divided into four groups with 6 lambs in each group. The lambs were fed with the basal diets supplemented with 0 (0 mg/kg group), 500 (500 mg/kg group), 1000 (1000 mg/kg group) and 1500 mg (1500 mg/kg group) GAA per kg diet (DM basis), respectively. The results showed that, as the GAA content of the diet increased, there was a quadratic change in DMI, with the lowest in the 500 mg/kg group and the highest in the 0 mg/kg group. The CK enzyme activity and ATP content in quadriceps muscle increased linearly with increasing levels of diary GAA in the diet. PCr levels and ADP levels in the longest dorsal muscle increased linearly with increasing levels of GAA in the diet. The relative expression of SLC6A6 and SLC6A8 mRNA in the jejunum and ileum mucosa showed a quadratic change as the dietary GAA level increased, with the lowest relative expression in both the 1500 mg/kg group. With the increase of dietary GAA level, both Cr concentration in hepatic vein plasma and the portal plasma GAA concentration shows a quadratic change, with the highest concentration in the 500 mg/kg group and the lowest concentration in the 0 mg/kg group. Therefore, dietary supplementation with 500~1000 mg/kg DM GAA is recommended for lambs.
Sarcopenia for outcomes in patients undergoing spinal surgery: A protocol for a systematic review and pooled analysis of observational studies

Background Sarcopenia is a progressive age-related skeletal muscle disorder characterized by decreased muscle mass and loss of muscle function. Recent studies have shown that sarcopenia is able to predict a variety of clinical outcomes after spinal surgery. Controversy still exists among previous reports in terms of the definition and measurement of sarcopenia, these findings are heterogeneous so far. Therefore, the aim of the current study is to assess the up-to-date evidence of sarcopenia for postoperative outcomes among people undergoing spinal surgery. Methods and analysis This protocol was carried out based on the preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) statement. It has been pre-registered in PROSPERO with the registration number of CRD42021260459. Three databases (including Pubmed, EMBASE, and Cochrane Library) will be searched from inception through May 10, 2021 to determine related cohort studies examining sarcopenia on multidimensional outcomes in patients undergoing spinal surgery. Major outcomes will be involved including mortality, morbidity, length of stay, postoperative complications or adverse events. DerSimonian & Laird random-effects meta-analysis will be used to calculate pooled odds ratio (OR) for binary data and pooled weighted mean differences (WMDs) or standardized mean differences (SMDs) for continuous data. The Newcastle-Ottawa Scale (NOS) will be used to assess the risk of bias of included studies. Narrative synthesis will be carried out if a pooled analysis is not possible. Ethics and dissemination Ethical approval is not required for this study as the data involved are from the published literatures. We intend to disseminate or share the results of the study in a peer-reviewed journal or at relevant conferences. PROSPERO registration number CRD42021260459.
Use of the Azure Kinect to measure foot clearance during obstacle crossing: A validation study

Obstacle crossing is a typical adaptive locomotion known to be related to the risk of falls. Previous conventional studies have used elaborate and costly optical motion capture systems, which not only represent a considerable expense but also require participants to visit a laboratory. To overcome these shortcomings, we aimed to develop a practical and inexpensive solution for measuring obstacle-crossing behavior by using the Microsoft Azure Kinect, one of the most promising markerless motion capture systems. We validated the Azure Kinect as a tool to measure foot clearance and compared its performance to that of an optical motion capture system (Qualisys). We also determined the effect of the Kinect sensor placement on measurement performance. Sixteen healthy young men crossed obstacles of different heights (50, 150, and 250 mm). Kinect sensors were placed in front of and beside the obstacle as well as diagonally between those positions. As indices of measurement quality, we counted the number of measurement failures and calculated the systematic and random errors between the foot clearance measured by the Kinect and Qualisys. We also calculated the Pearson correlation coefficients between the Kinect and Qualisys measurements. The number of measurement failures and the systematic and random error were minimized when the Kinect was placed diagonally in front of the obstacle on the same side as the trail limb. The high correlation coefficient (r > 0.890) observed between the Kinect and Qualisys measurements suggests that the Azure Kinect has excellent potential for measuring foot clearance during obstacle-crossing tasks.
Sex-specific lesion pattern of functional outcomes after stroke

Abstract Stroke represents a considerable burden of disease for both men and women. However, a growing body of literature suggests clinically relevant sex differences in the underlying causes, presentations and outcomes of acute ischaemic stroke. In a recent study, we reported sex divergences in lesion topographies: specific to women, acute stroke severity was linked to lesions in the left-hemispheric posterior circulation. We here determined whether these sex-specific brain manifestations also affect long-term outcomes. We relied on 822 acute ischaemic patients [age: 64.7 (15.0) years, 39% women] originating from the multi-centre MRI-GENIE study to model unfavourable outcomes (modified Rankin Scale >2) based on acute neuroimaging data in a Bayesian hierarchical framework. Lesions encompassing bilateral subcortical nuclei and left-lateralized regions in proximity to the insula explained outcomes across men and women (area under the curve = 0.81). A pattern of left-hemispheric posterior circulation brain regions, combining left hippocampus, precuneus, fusiform and lingual gyrus, occipital pole and latero-occipital cortex, showed a substantially higher relevance in explaining functional outcomes in women compared to men [mean difference of Bayesian posterior distributions (men – women) = −0.295 (90% highest posterior density interval = −0.556 to −0.068)]. Once validated in prospective studies, our findings may motivate a sex-specific approach to clinical stroke management and hold the promise of enhancing outcomes on a population level.
Strategic, feasibility, economic, and cultural aspects of phase 0 approaches

Research conducted over the past 2 decades has enhanced the validity and expanded the applications of microdosing and other phase 0 approaches in drug development. Phase 0 approaches can accelerate drug development timelines and reduce attrition in clinical development by increasing the quality of candidates entering clinical development and by reducing the time to “go‐no‐go” decisions. This can be done by adding clinical trial data (both healthy volunteers and patients) to preclinical candidate selection, and by applying methodological and operational advantages that phase 0 have over traditional approaches. The main feature of phase 0 approaches is the limited, subtherapeutic exposure to the test article. This means a reduced risk to research volunteers, and reduced regulatory requirements, timelines, and costs of first‐in‐human (FIH) testing. Whereas many operational aspects of phase 0 approaches are similar to those of other early phase clinical development programs, they have some unique strategic, regulatory, ethical, feasibility, economic, and cultural aspects. Here, we provide a guidance to these operational aspects and include case studies to highlight their potential impact in a range of clinical development scenarios.
Does Presurgical Nasoalveolar Molding Reduce the Need for Future Bone Grafting in Cleft Lip and Palate Patients? A Systematic Review and Meta-Analysis

Objective: Nasoalveolar molding (NAM) is a technique that is utilized in patients with cleft lip/palate before performing lip surgery. This procedure has been shown to result in a more aesthetic nose with lesser columellar deviation and reduced scaring. The aim of our study was to evaluate the long-term results of NAM and gingivoperiosteoplasty in patients with cleft lip and palate. Methods and Materials: An electronic search of databases (ie, PubMed, ISI Web of Science, EMBASE, Scopus, and Google Scholar) from inception to March 2021 was performed and after selecting the eligible studies, relevant data were collected using piloted extraction forms. The success rate of NAM and gingivoperiosteoplasty, and Bergland score were pooled using random-effects inverse variance meta-analysis. Results: Seven studies were included in this meta-analysis and systematic review. The pooled mean success rate of NAM with gingivoperiosteoplasty (GPP) based on the continuity of alveolar bone structure was 71% (95% confidence interval [CI] = 54–85). This means that in 71% of cases NAM + GPP treatment eliminated the need for future bone grafts. Also, no significant difference between the success rate (risk ratio = 1.00, 95% CI = 0.64–1.58) and mean Bergland score (mean difference = 0.64, 95% CI = −1.04 to 2.31) of NAM + GPP and skeletal bone graft was found. Conclusions: Nasoalveolar molding and gingivoperiosteoplasty was successful in 71% of cases treating patients with cleft lip and palate. This treatment is similar with the secondary alveolar bone graft in both the success rate and the alveolar height that it generates while being less invasive and with lower morbidity.
The vaccine-site microenvironment: impacts of antigen, adjuvant, and same-site vaccination on antigen presentation and immune signaling

Background A goal of cancer vaccines is to induce strong T cell responses to tumor antigens, but the delivery method, schedule, and formulation of cancer vaccines have not yet been optimized. Adjuvants serve to increase the immune response against vaccine antigens. However, little is known about the impact of adjuvants plus antigen and their delivery schedule on the immunologic milieu in the vaccine-site microenvironment (VSME). We hypothesized that antigen processing and presentation may occur directly in the VSME, that adding the toll-like receptor 3 (TLR3) agonist polyICLC (pICLC) would enhance markers of immune activation, and that the immune signatures would be enhanced further by repeated vaccination in the same skin site rather than after multiple vaccines in different skin locations. Methods Using RNA sequencing, we evaluated VSME biopsies from patients undergoing subcutaneous/intradermal peptide vaccination against melanoma, with incomplete Freund’s adjuvant (IFA) with or without pICLC. Differential gene expression analyses and gene set enrichment analyses were performed using R. False discovery rate corrected p values <0.05 were considered significant. Results We found that addition of peptide antigens to IFA enhanced antigen presentation pathways and a tertiary lymphoid structure gene-signature locally at the VSME. Addition of pICLC to IFA + peptide induced an immunologically favorable VSME 1 week after injection but had little impact on the VSME after three injections, compared with IFA + peptide alone. Repeated same-site injection of IFA + peptide antigens induced a VSME with more dendritic cell activation, Th1 dominance, and TLR adaptor protein gene expression than that induced by injections at different, rotating skin locations. Conclusions These data suggest that the vaccine-site itself may be a critically important location contributing to vaccine immunity rather than just the draining lymph node, that IFA induces a favorable VSME with TLR agonist being most beneficial early in the vaccine course, and that same-site injections lead to persistent stimulation of immune pathways that may be beneficial in eliciting antigen specific T cell expansion.
Predicting future community-level ocular Chlamydia trachomatis infection prevalence using serological, clinical, molecular, and geospatial data

Trachoma is an infectious disease characterized by repeated exposures to Chlamydia trachomatis (Ct) that may ultimately lead to blindness. Efficient identification of communities with high infection burden could help target more intensive control efforts. We hypothesized that IgG seroprevalence in combination with geospatial layers, machine learning, and model-based geostatistics would be able to accurately predict future community-level ocular Ct infections detected by PCR. We used measurements from 40 communities in the hyperendemic Amhara region of Ethiopia to assess this hypothesis. Median Ct infection prevalence among children 0–5 years old increased from 6% at enrollment, in the context of recent mass drug administration (MDA), to 29% by month 36, following three years without MDA. At baseline, correlation between seroprevalence and Ct infection was stronger among children 0–5 years old (ρ = 0.77) than children 6–9 years old (ρ = 0.48), and stronger than the correlation between active trachoma and Ct infection (0-5y ρ = 0.56; 6-9y ρ = 0.40). Seroprevalence was the strongest concurrent predictor of infection prevalence at month 36 among children 0–5 years old (cross-validated R2 = 0.75, 95% CI: 0.58–0.85), though predictive performance declined substantially with increasing temporal lag between predictor and outcome measurements. Geospatial variables, a spatial Gaussian process, and stacked ensemble machine learning did not meaningfully improve predictions. Serological markers among children 0–5 years old may be an objective tool for identifying communities with high levels of ocular Ct infections, but accurate, future prediction in the context of changing transmission remains an open challenge.
Hope pictured in drawings by patients newly diagnosed with advanced cancer.

BACKGROUND Hope is an integral part of a dying person's needs and an important phenomenon that has not been satisfactorily explored. The tension between hope for a cure and the reality of being terminally ill is a paradox, which in the context of palliative cancer care, nurses and health care professionals must take into consideration. OBJECTIVE The purpose of this study was to elucidate the phenomenon of hope and to investigate the lived experiences of hope among newly diagnosed patients with advanced cancer. METHOD The study used a phenomenological-visual method where drawings and post-drawing interviews were used. The participants were six patients who recently had been offered specialised palliative care treatment. They were five women and one man with different cancer diagnoses and between 30 and 82 years of age (median 65 years). The data consisted of six drawings and individual post-drawing interviews with the participants. The study was reported using the COREQ checklist. RESULTS The study revealed one main concern 'Being in hope' and hope appeared in four different dimensions; internal, external, relational and transcendental. Hopelessness was present at all times. CONCLUSION Hope pictured in drawings was expressed through colour, shape, lines, symbols and metaphors, and hope incorporated internal, external, relational and transcendental aspects. Hope was constantly fighting against hopelessness and hope integrated with past, present and future. RELEVANCE TO CLINICAL PRACTICE Drawings, as well as other visual representations, are suitable tools when trying to understand an ineffable phenomenon such as hope experienced by people newly diagnosed with cancer.
Bacterioboat—A novel tool to increase the half-life period of the orally administered drug

The short half-life in the GI tract necessitates an excess of drugs causing side effects of oral formulations. Here, we report the development and deployment of Bacterioboat, which consists of surface-encapsulated mesoporous nanoparticles on metabolically active Lactobacillus reuteri as a drug carrier suitable for oral administration. Bacterioboat showed up to 16% drug loading of its dry weight, intestinal anchorage around alveoli regions, sustained release, and stability in physiological conditions up to 24 hours. In vivo studies showed that oral delivery of 5-fluorouracil leads to increased potency, resulting in improved shrinkage of solid tumors, enhanced life expectancy, and reduced side effects. This novel design and development make this system ideal for orally administrable drugs with low solubility or permeability or both and even making them effective at a lower dose.
Sex differences in sudden cardiac death in a nationwide study of 54 028 deaths

Objective Sudden cardiac death (SCD) is a leading cause of death and is more common among males than females. Epidemiological studies of sex differences in SCD cases of all ages are sparse. The aim of this study was to examine differences in incidence rates, clinical characteristics, comorbidities and autopsy findings between male and female SCD cases. Methods All deaths in Denmark in 2010 (54 028) were reviewed. Autopsy reports, death certificates, discharge summaries and nationwide health registries were reviewed to identify cases of SCD. Based on the available information, all deaths were subcategorised into definite, probable and possible SCD. Results A total of 6867 SCD cases were identified, of which 3859 (56%) were males and 3008 (44%) were females. Incidence rates increased with age and were higher for male population across all age groups in the adult population. Average age at time of SCD was 71 years among males compared with 79 among females (p<0.01). The greatest difference in SCD incidence between males and females was found among the 35–50 years group with an incidence rate ratio of 3.7 (95% CI: 2.8 to 4.8). Compared with female SCD victims, male SCD victims more often had cardiovascular diseases and diabetes mellitus (p<0.01). Conclusion This is the first nationwide study of sex differences in SCD across all ages. Differences in incidence rates between males and females were greatest among young adults and the middle-aged. Incidence rates of SCD among older female population approached that of the male population, despite having significantly more cardiovascular disease and diabetes in male SCD cases.