Miracle-dz/UniFAR-FTUs huggingface dataset:
VGF in Cerebrospinal Fluid Combined With Conventional Biomarkers Enhances Prediction of Conversion From MCI to AD.

BACKGROUND Previous work has suggested that the brain and cerebrospinal fluid (CSF) levels of a neural protein involved in synaptic transmission, VGF (a noninitialism), may be altered in mild cognitive impairment (MCI) and Alzheimer Disease (AD). The objective of the current work is to examine the potential of CSF levels of a peptide derived from VGF to predict conversion from MCI to AD. MATERIALS AND METHODS Using multivariate analytical approaches, the performance of the conventional biomarkers (CSF Aβ1-42 and phosphorylated tau +/- hippocampal volume) was compared with the same biomarkers combined with CSF VGF peptide levels in a large publicly available data set from human subjects. RESULTS It was observed that VGF peptides are lowered in CSF of patients with AD compared with controls and that combinations of CSF Aβ1-42 and phosphorylated tau, hippocampal volume, and VGF peptide levels outperformed conventional biomarkers alone (hazard ratio=2.2 vs. 3.9), for predicting MCI to AD conversion. CONCLUSIONS CSF VGF enhances the ability of conventional biomarkers to predict MCI to AD conversion. Future work will be needed to determine the specificity of VGF for AD versus other neurodegenerative diseases.
Output tracking actuator failure compensation control

Controller parametrization is crucial for control of systems with actuator failures. Certain conditions on the controlled system are needed for a parametrization suitable for meeting a given control objective. For actuator failure compensation, it is desirable to use less restrictive conditions which mean that larger classes of systems can be candled with a fixed or adaptive compensation controller. In this paper, a minimal necessary and sufficient condition for stable plant-model output matching is derived, with analytical proof, for two actuator failure models: failures with fixed or variant values. An adaptive control scheme is developed for systems with unknown dynamics parameters and actuator failure parameters including failure values, times and patterns.
A comparison of optimal and sub-optimal MAP decoding algorithms operating in the log domain

For estimating the states or outputs of a Markov process, the symbol-by-symbol MAP algorithm is optimal. However, this algorithm, even in its recursive form, poses technical difficulties because of numerical representation problems, the necessity of nonlinear functions and a high number of additions and multiplications. MAP like algorithms operating in the logarithmic domain presented in the past solve the numerical problem and reduce the computational complexity, but are suboptimal especially at low SNR (a common example is the max-log-MAP because of its use of the max function). A further simplification yields the soft-output Viterbi algorithm (SOVA). We present a log-MAP algorithm that avoids the approximations in the max-log-MAP algorithm and hence is equivalent to the true MAP, but without its major disadvantages. We compare the (log-)MAP, max-log-MAP and SOVA from a theoretical point of view to illuminate their commonalities and differences. As a practical example forming the basis for simulations, we consider Turbo decoding, where recursive systematic convolutional component codes are decoded with the three algorithms, and we also demonstrate the practical suitability of the log-MAP by including quantization effects. The SOVA is, at 10/sup -4/, approximately 0.7 dB inferior to the (log-)MAP, the max-log-MAP lying roughly in between. We also present some complexity comparisons and conclude that the three algorithms increase in complexity in the order of their optimality.
Institutional barriers and enablers to implementing and complying with internationally accepted quality standards in the local pharmaceutical industry of Pakistan: a qualitative study

Abstract Complying with good manufacturing practices (GMP) and ensuring a quality system is integral to production and supply of quality medicines and achieving universal health coverage. This study focus on the local production of medicines in Pakistan, a lower middle-income country that has observed considerable growth in the number of pharmaceutical companies over the past two decades. Against this background, we investigated: (1) How is quality assurance (QA) and GMP compliance understood and acted upon by local pharmaceutical manufacturers? ; (2) What are the institutional barriers and enablers for QA and GMP compliance in the local pharmaceutical sector from the perspective of key stakeholders? ; and (3) What are the institutional barriers and enablers for strengthening local regulatory capacity to improve QA in the industry in the long term? We used a qualitative study design involving 22 interviews of the drug regulatory bodies (n = 9), academia (n = 3) and local manufacturers (n = 10), identifying key themes in data by thematic analysis. Document analysis was used to collect additional information and supplement the interview data. We identified that manufacturing facilities operated under different GMP standards and interpretations, pointing towards an absence of harmonization in quality standards across the industry. Views diverged about the status of GMP compliance, with interviewees from academia presenting a more critical view compared with regulators who promoted a more positive story. Among the barriers explaining why companies struggled with quality standards, the lack of a mindset promoting quality and safety among profit-oriented manufacturers was prominent. At the federal level, DRAP’s establishment represented an institutional improvement aiming to promote QA through inspections and guidance. While some positive measures to promote quality have been observed, the need for DRAP to strengthen its technical and regulatory capacity, enhance its engagement in international collaboration and learning, and improve transparency and accountability were highlighted. Overall, since the challenges in Pakistan are shared with other low- and middle-income countries with local production, there is a need to commit to international collaborative mechanisms, such as those lead by WHO, on this issue.
A protocol for systematic review and meta-analysis

Background:Human epididymis protein 4 (HE4) protein has garnered a great degree of interest as a complementary biomarker to carbohydrate antigen 125 (CA125), or even as an independent biomarker for monitoring, diagnosis, and prognostication of ovarian cancer. Its use is currently limited to ovarian cancer. Recent studies have suggested that it could also be used in other types of cancers. Methods: The Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) guidelines was used to design this meta-analysis protocol. The final study will also be conducted under the PRISMA guidelines for systematic reviews and meta-analyses. The core bibliographic database search will be carried out by 2 reviewers working individually, with each conducting an initial screening based on titles and abstracts. The shortlisted articles will be selected for review and statistical analysis based on predefined inclusion and exclusion criteria. Study characteristics, relevant clinicopathological characteristics and statistical data required for meta-analysis (hazard ratios [HRs] and 95% confidence interval [CIs) will be extracted and compiled into a MS Excel datasheet. Meta-analysis will be performed, using a random-effects model, and the results (pooled HR and 95%CI) will be presented in the form of a forest plot. Publication bias will also be assessed by use of Egger bias indicator test and funnel plot symmetry. If data are insufficient, a narrative line of review will be pursued. Discussion:HE4 protein has been shown to have great potential for clinical use as a diagnostic and prognostic marker in epithelial ovarian cancer (EOC). However, HE4 is not only limited to expression in ovarian cancer, but is also overexpressed in lung and endometrial cancers. The effectiveness of HE4 as a biomarker in cancers (other than EOC) has not yet been studied in the form of a comprehensive systematic review and meta-analysis. The results of this study should allow for expanded use of HE4 as a multiutility biomarker in multiple cancer types, thereby, elevating HE4’s value as a cancer biomarker. PROSPERO registration: CRD42019120326. Abbreviations: CA125 = carbohydrate antigen 125, EOC = epithelial ovarian cancer, HE4 = human epididymis protein 4, HR = hazard ratio, PRISMA = preferred reporting items for systematic reviews and meta-analysis protocols.
Kinematic Evaluation of the GMK Sphere Implant During Gait Activities: A Dynamic Videofluoroscopy Study

Joint stability is a primary concern in total knee joint replacement. The GMK Sphere prosthesis was specifically designed to provide medial compartment anterior–posterior (A–P) stability, while permitting rotational freedom of the joint through a flat lateral tibial surface. The objective of this study was to establish the changes in joint kinematics introduced by the GMK Sphere prosthesis during gait activities in comparison to conventional posterior‐stabilized (PS) fixed‐bearing and ultra‐congruent (UC) mobile‐bearing geometries. The A–P translation and internal/external rotation of three cohorts, each with 10 good outcome subjects (2.9 ± 1.6 years postop), with a GMK Sphere, GMK PS or GMK UC implant were analysed throughout complete cycles of gait activities using dynamic videofluoroscopy. The GMK Sphere showed the smallest range of medial compartment A–P translation for level walking, downhill walking, and stair descent (3.6 ± 0.9 mm, 3.1 ± 0.8 mm, 3.9 ± 1.3 mm), followed by the GMK UC (5.7 ± 1.0 mm, 8.0 ± 1.7 mm, 8.7 ± 1.9 mm) and the GMK PS (10.3 ± 2.2 mm, 10.1 ± 2.6 mm, 11.6 ± 1.6 mm) geometries. The GMK Sphere exhibited the largest range of lateral compartment A–P translation (12.1 ± 2.2 mm), and the largest range of tibial internal/external rotation (13.2 ± 2.2°), both during stair descent. This study has shown that the GMK Sphere clearly restricts A–P motion of the medial condyle during gait activities while still allowing a large range of axial rotation. The additional comparison against the conventional GMK PS and UC geometries, not only demonstrates that implant geometry is a key factor in governing tibio‐femoral kinematics, but also that the geometry itself probably plays a more dominant role for joint movement than the type of gait activity. © 2019 The Authors. Journal of Orthopaedic Research® published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society. J Orthop Res 37:2337–2347, 2019
Intimate Partner Violence and Material Hardship Among Urban Mothers

Using a longitudinal population-based sample (n = 4,234), this study explored the association of intimate partner violence (IPV) with material hardship. We found that women who experienced IPV are substantially more likely to experience material hardship, even after controlling for a comprehensive set of static and time-varying characteristics, including material hardship at the prior wave and individual fixed effects. Associations were strongest for experiences of physical abuse (the least prevalent type of IPV) and controlling abuse (the most prevalent type of IPV) but were weaker for emotional abuse. Results suggest that IPV increases the probability of material hardship by 10-25%.
Measuring Innovation Culture: Development and Validation of a Multidimensional Questionnaire

Aims: In this paper, we describe the design and validation of the Radiography of Innovation Culture-Multidimensional Questionnaire (RIC-MQ), aimed at studying innovation culture in organizations from the perspective of individuals in addition to taking context into account. It has been considered that innovation culture is essential to enhance the innovation capability of organizations, but studies of innovation culture adopting a holistic approach are scarce. Those identified in the literature tend to pay little attention to the influence of individuals within the organization or to social context. Study Design: Cross-sectional study. Place and Duration of Study: The questionnaire was sent to a sample of workers from three Spanish organizations (a public research organization, a public university and a private healthcare company) to gather data and analyse RIC-MQ psychometric properties. Data were collected between October 2011 and November 2011. Methodology: Cronbach’s alpha coefficients were used to assess reliability, and Structural Original Research Article Munoz-van den Eynde et al.; AIR, 4(2): 122-141, 2015; Article no.AIR. 2015.068 123 Equation Modelling (SEM) to validate the RIC-MQ. Results: The RIC-MQ includes three dimensions: general, organizational and individual. Reliability, construct validity and discriminant validity results are satisfactory. The three dimensions structure has been confirmed and 15 factors have been identified. Conclusion: Results provide evidence supporting the adequacy of the questionnaire to measure innovation culture as a three dimensional construct from an individual perspective in a sample of Spanish workers.
A cross-sectional descriptive analysis of portrayal of autism spectrum disorders in YouTube videos: A short report

Professionals have expressed concerns about the quality of autism-related information available from Internet-based sources. The purpose of this study was to examine the source, content, usability, and actionability of autism spectrum disorder–related information contained in 100 different videos directed to families of children with autism spectrum disorder uploaded to YouTube. Upload sources were identified, and video content was coded. Understandability and actionability of the videos were examined using Patient Education Materials Assessment Tool for Audiovisual Materials. The collective number of views of the videos was almost 100 million. The length of videos was 691.17 min (i.e. 11.5 h) with the shortest video being 30 s and the longest video being 37.36 min. The YouTube videos related to autism spectrum disorder covered a range of issues, although much of the content was focused on signs and symptoms. No difference in content reporting was noted based on sources for most categories, although differences were noted in some categories (e.g. professionals mentioned diagnosis and resources more frequently). Poor understandability and actionability scores (i.e. below 70%) were reported for all videos regardless of video source. However, the videos generated by the professionals were superior in terms of understandability. Study implications and recommendations for further research are discussed.
Accurate Identification of Mass Peaks for Tandem Mass Spectra Using MCMC Model

In proteomics, many methods for the identification of proteins have been developed. However, because of limited known genome sequences, noisy data, incomplete ion sequences, and the accuracy of protein identification,it is challenging to identify peptides using tandem mass spectral data. Noise filtering and removing thus play a key role in accurate peptide identification from tandem mass spectra. In this paper, we employ a Bayesian model to identify proteins based on the prior information of bond cleavages. A Markov Chain Monte Carlo(MCMC)algorithm is used to simulate candidate peptides from the posterior distribution and to estimate the parameters for the Bayesian model. Our simulation and computational experimental results show that the model can identify peptide with a higher accuracy.
Decomposition feature selection with applications in detecting correlated biomarkers of bipolar disorders

Feature selection is an important initial step of exploratory analysis in biomedical studies. Its main objective is to eliminate the covariates that are uncorrelated with the outcome. For highly correlated covariates, traditional feature selection methods, such as the Lasso, tend to select one of them and eliminate the others, although some of the eliminated ones are still scientifically valuable. To alleviate this drawback, we propose a feature selection method based on covariate space decomposition, referred herein as the “Decomposition Feature Selection” (DFS), and show that this method can lead to scientifically meaningful results in studies with correlated high dimensional data. The DFS consists of two steps: (i) decomposing the covariate space into disjoint subsets such that each of the subsets contains only uncorrelated covariates and (ii) identifying significant predictors by traditional feature selection within each covariate subset. We demonstrate through simulation studies that the DFS has superior practical performance over the Lasso type methods when multiple highly correlated covariates need to be retained. Application of the DFS is demonstrated through a study of bipolar disorders with correlated biomarkers.
Exposure to ambient air pollution and the incidence of lung cancer and breast cancer in the Ontario Population Health and Environment Cohort

Lung and female breast cancers are highly prevalent worldwide. Although the association between exposure to ambient fine particulate matter (PM2.5) and lung cancer has been recognized, there is less evidence for associations with other common air pollutants such as nitrogen dioxide (NO2) and ozone (O3). Even less is known about potential associations between these pollutants and breast cancer. We conducted a population‐based cohort study to investigate the associations of chronic exposure to PM2.5, NO2, O3 and redox‐weighted average of NO2 and O3 (Ox) with incident lung and breast cancer, using the Ontario Population Health and Environment Cohort (ONPHEC), which includes all long‐term residents aged 35–85 years who lived in Ontario, Canada, 2001–2015. Incident lung and breast cancers were ascertained using the Ontario Cancer Registry. Annual estimates of exposures were assigned to the residential postal codes of subjects for each year during follow‐up. We used Cox proportional‐hazards models adjusting for personal‐ and neighborhood‐level covariates. Our cohorts for lung and breast cancer analyses included ~4.9 million individuals and ~2.5 million women, respectively. During follow‐up, 100,146 incident cases of lung cancer and 91,146 incident cases of breast cancer were diagnosed. The fully adjusted analyses showed positive associations of lung cancer incidence with PM2.5 (hazard ratio [HR] = 1.02 [95% CI: 1.01–1.05] per 5.3 μg/m3) and NO2 (HR = 1.05 [95% CI: 1.03–1.07] per 14 ppb). No associations with lung cancer were observed for O3 or Ox. Relationships between PM2.5 and NO2 with lung cancer exhibited a sublinear shape. We did not find compelling evidence linking air pollution to breast cancer.
In Vitro Rearing of the Parasitoid Exorista larvarum (Diptera: Tachinidae) from Eggs Laid Out of Host

Abstract We evaluated the possibility of using the eggs laid out of host to rear Exorista larvarum (L.) (Diptera: Tachinidae), a larval parasitoid of Lepidoptera, on artificial media. In a first experiment, eggs oviposited on a plastic sheet (either by inexperienced or experienced females) showed the same in vitro hatching capability as those removed from the larvae of the factitious host Galleria mellonella L. Subsequently, eggs laid on the host integument or out of host, either by inexperienced or experienced females, were removed from the oviposition substrate and placed on a skimmed milk-based artificial medium. The percentages of hatched eggs, of puparia and adults, as well as the puparial weights did not differ significantly among the three treatments. These findings suggested that E. larvarum may be successfully reared in vitro with a total exclusion of the host insect. In a further test, no difference for the in vitro hatching time was found between the eggs oviposited either on a plastic sheet or on G. mellonella larvae in the same length of time (60 min). This result suggested that at oviposition the out-of-host eggs were unincubated, similarly to those that had been laid on the host larvae.
Identification and analysis of genes associated with head and neck squamous cell carcinoma by integrated bioinformatics methods

Head and neck squamous cell carcinoma (HNSCC) is one of the most common cancers worldwide, exhibiting high morbidity and mortality. The prognosis of HNSCC patients has remained poor, though considerable efforts have been made to improve the treatment of this cancer. Therefore, identifying significant differentially expressed genes (DEGs) involved in HNSCC progression and exploiting them as novel biomarkers or potential therapeutic targets for HNSCC is highly valuable.
Nabiximols for the Treatment of Cannabis Dependence: A Randomized Clinical Trial.

Importance There are no effective medications for treating dependence on cannabis. Objective To examine the safety and efficacy of nabiximols in the treatment of patients with cannabis dependence. Design, Setting, and Participants This parallel double-blind randomized clinical trial comparing nabiximols with placebo in a 12-week, multisite outpatient study recruited participants from February 3, 2016, to June 14, 2017, at 4 outpatient specialist alcohol and drug treatment services in New South Wales, Australia. Participants had cannabis dependence (as defined by the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision) and were seeking treatment, were nonresponsive to prior treatment attempts, were 18 to 64 years of age, had no other substance use disorder, had no severe medical or psychiatric conditions, were not pregnant, were not mandated by a court to undergo treatment, and provided informed consent. Results for primary efficacy measures and all secondary outcomes were obtained using a modified intention-to-treat data set. Interventions Participants received 12-week treatment involving weekly clinical reviews, structured counseling, and flexible medication doses-up to 32 sprays daily (tetrahydrocannabinol, 86.4 mg, and cannabidiol, 80 mg), dispensed weekly. Main Outcomes and Measures Primary outcome was self-reported number of days using illicit cannabis during the 12-week period. Other outcomes included alternate cannabis use parameters (periods of abstinence, withdrawal, cravings, and problems), safety parameters (adverse events and aberrant medication use), health status, other substance use, and treatment retention. Results A total of 128 participants (30 women and 98 men; mean [SD] age, 35.0 [10.9] years) were randomized and received at least 1 dose of study medication. Participants had used a mean (SD) of 2.3 (2.1) g of cannabis on a mean (SD) of 25.7 (4.5) days in the past 28 days. Treatment retention was comparable for the 2 groups (placebo, 30 of 67 participants [44.8%]; nabiximols, 30 of 61 participants [49.2%]), and both groups used similar mean (SD) doses (placebo, 18.5 [9.5] sprays daily; nabiximols, 17.6 [9.5] sprays daily, equivalent to a mean [SD] of 47.5 [25.7] mg of tetrahydrocannabinol and 44.0 [23.8] mg of cannabidiol). For the primary end point, the placebo group reported significantly more days using cannabis during the 12 weeks (mean [SD], 53.1 [33.0] days) than the nabiximols group (mean [SD], 35.0 [32.4] days; estimated difference, 18.6 days; 95% CI, 3.5-33.7 days; P = .02). Both groups showed comparable improvements in health status, with no substantial changes in other substance use. Medication was well tolerated with few adverse events. Conclusions and Relevance This study demonstrates that cannabinoid agonist treatment, in this case using nabiximols, in combination with psychosocial interventions is a safe approach for reducing cannabis use among individuals with cannabis dependence who are seeking treatment. Trial Registration anzctr.org. au Identifier: ACTRN12616000103460.