Miracle-dz/UniFAR-FTUs huggingface dataset:
Pharmacokinetics of single- and multiple-dose roflumilast: an open-label, three-way crossover study in healthy Chinese volunteers

Purpose To determine the pharmacokinetic properties of the common tablet of roflumilast administered in single and multiple oral doses in Chinese subjects. Subjects and methods Both the single- and multiple-dose studies included 12 adults (6 males and 6 females). In this single-center, open-label study, single doses of 0.25, 0.375, and 0.5 mg were administered using a randomized, three-way crossover design, and then, the 0.375 mg dose was continued for 11 days once daily. The pharmacokinetic parameters for roflumilast and roflumilast N-oxide were determined and the safety evaluation included adverse events assessed by monitoring, physical examination, vital sign tests, and clinical laboratory tests. Results After every single dose, the time to the maximum concentration (Cmax) of roflumilast (Tmax) was 0.25–2.0 hours; thereafter, the concentration declined, with a mean half-life (t1/2) of 19.7–20.9 hours over the range of 0.25–0.50 mg. As for roflumilast N-oxide, the mean t1/2 was 23.2–26.2 hours. The area under curve from the beginning to 24 hours (AUC0–24 h), the AUC until infinity (AUCinf), and the Cmax of roflumilast and roflumilast N-oxide increased in a dose-proportional manner. After multiple doses, the accumulation index (Rac) on the 11th day of the steady state was ~1.63 for roflumilast and 3.20 for roflumilast N-oxide. No significant sex differences were observed in the pharmacokinetic parameters of roflumilast and roflumilast N-oxide. In addition, there were no serious adverse events across the trial. Conclusion Roflumilast was safe and well-tolerated in healthy volunteers, and a linear increase in its Cmax and AUC values was observed at doses ranging from 0.25 to 0.50 mg.
Simultaneous cosegmentation of tumors in PET‐CT images using deep fully convolutional networks

PURPOSE To investigate the use and efficiency of 3-D deep learning, fully convolutional networks (DFCN) for simultaneous tumor cosegmentation on dual-modality nonsmall cell lung cancer (NSCLC) and positron emission tomography (PET)-computed tomography (CT) images. METHODS We used DFCN cosegmentation for NSCLC tumors in PET-CT images, considering both the CT and PET information. The proposed DFCN-based cosegmentation method consists of two coupled three-dimensional (3D)-UNets with an encoder-decoder architecture, which can communicate with the other in order to share complementary information between PET and CT. The weighted average sensitivity and positive predictive values denoted as Scores, dice similarity coefficients (DSCs), and the average symmetric surface distances were used to assess the performance of the proposed approach on 60 pairs of PET/CTs. A Simultaneous Truth and Performance Level Estimation Algorithm (STAPLE) of 3 expert physicians' delineations were used as a reference. The proposed DFCN framework was compared to 3 graph-based cosegmentation methods. RESULTS Strong agreement was observed when using the STAPLE references for the proposed DFCN cosegmentation on the PET-CT images. The average DSCs on CT and PET are 0.861 ± 0.037 and 0.828 ± 0.087, respectively, using DFCN, compared to 0.638 ± 0.165 and 0.643 ± 0.141, respectively, when using the graph-based cosegmentation method. The proposed DFCN cosegmentation using both PET and CT also outperforms the deep learning method using either PET or CT alone. CONCLUSIONS The proposed DFCN cosegmentation is able to outperform existing graph-based segmentation methods. The proposed DFCN cosegmentation shows promise for further integration with quantitative multimodality imaging tools in clinical trials.
Time Course of Upper Limb Function in Children with Unilateral Cerebral Palsy: A Five-Year Follow-Up Study

Knowledge on long-term evolution of upper limb function in children with unilateral cerebral palsy (CP) is scarce. The objective was to report the five-year evolution in upper limb function and identify factors influencing time trends. Eighty-one children (mean age 9 y and 11 mo, SD 3 y and 3 mo) were assessed at baseline with follow-up after 6 months, 1, and 5 years. Passive range of motion (PROM), tone, muscle, and grip strength were assessed. Activity measurements included Melbourne Assessment, Jebsen-Taylor test, Assisting Hand Assessment (AHA), and ABILHAND-Kids. At 5-year follow-up, PROM (p < 0.001) and AHA scores (p < 0.001) decreased, whereas an improvement was seen for grip strength (p < 0.001), Melbourne Assessment (p = 0.003), Jebsen-Taylor test (p < 0.001), and ABILHAND-Kids (p < 0.001). Age influenced the evolution of AHA scores (p = 0.003), with younger children being stable over time, but from 9 years onward, children experienced a decrease in bimanual performance. Manual Ability Classification System (MACS) levels also affected the evolution of AHA scores (p = 0.02), with stable scores in MACS I and deterioration in MACS II and III. In conclusion, over 5 years, children with unilateral CP develop more limitations in PROM, and although capacity measures improve, the spontaneous use of the impaired limb in bimanual tasks becomes less effective after the age of 9 years.
Association of author's financial conflict of interest with characteristics and outcome of rheumatoid arthritis randomized controlled trials.

Objectives To examine the prevalence, types and temporal trends of reported financial conflicts of interest (FCOIs) among authors of drug therapy randomized controlled trials (RCTs) for RA and their association with study outcomes. Methods We identified original, non-phase 1, parallel-group, drug therapy RA RCTs published in the years 2002-03, 2006-07, and 2010-11. Two investigators independently obtained trial characteristics data. Authors' FCOIs were classified as honoraria/consultation fees receipt, employee status, research grant, and stock ownership. Multivariable logistic regression was performed to identify whether FCOIs were independently associated with study outcome. Results A total of 146 eligible RCTs were identified. Of these, 83 (58.4%) RCTs had at least one author with an FCOI [employee status: 63 (43.2%), honoraria/consultation fees receipt: 49 (33.6%), research grant: 30 (20.5%), and stock ownership: 28 (19.2%)]. A remarkable temporal increase in reporting of honoraria/consultation fees receipt, research grant, and stock ownership was seen. The reporting of any FCOI itself was not associated with positive outcome [50/73 (68.5%) with author FCOI vs 36/52 (69.2%) without author FCOI, P = 0.93]. However, honoraria/consulting fees receipt was independently associated with increased likelihood of a positive outcome [adjusted odds ratio (95% CI) of 3.24 (1.06-9.88)]. In general, trials with FCOIs were significantly more likely to be multicentre, have larger enrolment, use biologic or a small molecule as the experimental intervention, and have better reporting of some methodological quality measures. Conclusion FCOI reporting in RA drug RCT authors is common and temporally increasing. Receipt of honoraria/consulting fees was independently associated with a positive study outcome.
Bidirectional Recurrent Auto-Encoder for Photoplethysmogram Denoising

Photoplethysmography (PPG) has become ubiquitous with the development of smart watches and the mobile healthcare market. However, PPG is vulnerable to various types of noises that are ever present in uncontrolled environments, and the key to obtaining meaningful signals depends on successful denoising of PPG. In this context, algorithms have been developed to denoise PPG, but many were validated in controlled settings or are reliant on multiple steps that must all work correctly. This paper proposes a novel PPG denoising algorithm based on bidirectional recurrent denoising auto-encoder (BRDAE) that requires minimal pre-processing steps and have the benefit of waveform feature accentuation beyond simple denoising. The BRDAE was trained and validated on a dataset with artificially augmented noise, and was tested on a large open database of PPG signals collected from patients enrolled in intensive care units as well as from PPG data collected intermittently during the daily routine of nine subjects over 24 h. Denoising with the trained BRDAE improved signal-to-noise ratio of the noise-augmented data by 7.9 dB during validation. In the test datasets, the denoised PPG showed statistically significant improvement in heart rate detection as compared with the original PPG in terms of correlation to reference and root-mean-squared error. These results indicate that the proposed method is an effective solution for denoising the PPG signal, and promises values beyond traditional denoising by providing PPG feature accentuation for pulse waveform analysis.
Parental chronic pain and internalizing symptoms in offspring: the role of adolescents’ social competence – the HUNT study

Background A growing body of research suggests that the children of parents with chronic pain are at risk for internalizing symptoms. The mechanisms of such associations have not been as thoroughly examined. The aim of the present study was to investigate whether adolescents’ social competence mediates the association between parental chronic pain and offspring internalizing symptoms as well as whether these associations are moderated by adolescent gender. Methods The current study was based on cross-sectional data from the Nord-Trøndelag Health Study (HUNT 3), a Norwegian population-based health survey conducted in 2006–2008. The present sample comprised adolescents who had both parents participating (n=9,681). Structural equation modeling was used for the data analysis. Results Our results indicated that the association between concurrent maternal and paternal chronic pain and offspring’s symptoms of anxiety and depression was partly mediated by low social competence for girls (b(SE)=0.060 [0.030], P=0.043) but not for boys (b(SE)=−0.059 [0.040], P=0.146). This suggests that these associations are moderated by offspring gender. Conclusion The study extends the existing literature on the possible pathways between parental chronic pain and internalizing symptoms in the offspring. Identifying protective factors in the pathways between parental chronic pain and mental distress in children could guide measures that promote the wellbeing of the child and family of chronic pain sufferers.
The Fluidity of Gender and Implications for the Biology of Inclusion for Transgender and Intersex Athletes.

One of the most contentious issues in modern day sport arises when sports are divided into male and female categories. The International Association of Athletics Federations' (IAAF) previous policy regulating intersex athletes was suspended by the Court of Arbitration for Sport (CAS), resulting in a new policy. The challenge faced by the governing body of athletics is to formulate a policy that upholds both international law and the Olympic charter that stipulates athletes compete without discrimination of any kind. Implementation of the policy has been delayed until after a verdict, expected no later than March 26, 2019, in the Semenya versus IAAF trial in the Court of Arbitration for Sport. If the policy is enacted, it will restrict athletes from competing in the female athletics category with specific differences of sex development (DSD) in races from 400 m up to the mile in international level competitions unless they lower their natural testosterone (T) levels below 5 nmol·L. To thoroughly assess this new IAAF policy, one needs to appreciate its legal, sociological, and scientific underpinnings but also the history of previous policies attempting to define precisely how athletes should be divided into male and female categories. We previously proposed a system to deal with gender variant athletes that relied on a determination of an "athlete/athletic gender. " The concept of "athlete gender" was presented to multiple audiences, and the resulting survey is included. A large majority of participants (71% of 153) who answered the survey agreed with the idea of an athlete gender. This position also was accompanied by the request for more studies (20% of those who agreed) and concern over the process of hormone monitoring (32% of those who agreed) to avoid doping misuse. The primary argument of those participating in the survey that disagreed with the position (23% of 153) was that biological differences between males and females remained even after the transition (47% of opposing comments). Mixed gender/sex competitions provide unique opportunities for athletes to compete against one another outside of the traditional male/female divide and pave the way for a more flexible approach for dealing with gender variant athletes.
Light Field Spatial Super-Resolution Using Deep Efficient Spatial-Angular Separable Convolution

Light field (LF) photography is an emerging paradigm for capturing more immersive representations of the real world. However, arising from the inherent tradeoff between the angular and spatial dimensions, the spatial resolution of LF images captured by commercial micro-lens-based LF cameras is significantly constrained. In this paper, we propose effective and efficient end-to-end convolutional neural network models for spatially super-resolving LF images. Specifically, the proposed models have an hourglass shape, which allows feature extraction to be performed at the low-resolution level to save both the computational and memory costs. To fully make use of the 4D structure information of LF data in both the spatial and angular domains, we propose to use 4D convolution to characterize the relationship among pixels. Moreover, as an approximation of 4D convolution, we also propose to use spatial-angular separable (SAS) convolutions for more computationally and memory-efficient extraction of spatial-angular joint features. Extensive experimental results on 57 test LF images with various challenging natural scenes show significant advantages from the proposed models over the state-of-the-art methods. That is, an average PSNR gain of more than 3.0 dB and better visual quality are achieved, and our methods preserve the LF structure of the super-resolved LF images better, which is highly desirable for subsequent applications. In addition, the SAS convolution-based model can achieve three times speed up with only negligible reconstruction quality decrease when compared with the 4D convolution-based one. The source code of our method is available online.
Self-Reported Suicidal Ideation as a Predictor of Suicidal Behavior Among Outpatients With Diagnoses of Psychotic Disorders.

OBJECTIVE: Individuals with psychotic disorders are at high risk of suicidal behavior. The study examined whether response to item 9 of the Patient Health Questionnaire (PHQ-9), which asks about thoughts of death or self-harm, predicts suicidal behavior among outpatients with diagnoses of psychotic disorders. METHODS: Electronic health records (EHRs) from seven large integrated health systems were used to identify all outpatient visits by adults with a diagnosis of schizophrenia spectrum psychosis or unspecified psychosis from January 1, 2009, to June 30, 2015, during which a PHQ-9 was completed (N=32,982 visits by 5,947 patients). Suicide attempts over the 90 days following each visit were ascertained from EHRs and insurance claims. Suicide deaths were ascertained from state death certificate files. RESULTS: Risk of suicide attempt within 90 days of an outpatient visit was . 8% among patients reporting no thoughts of death or self-harm and 3.5% among those reporting such thoughts "nearly every day. " Over 90 days of follow-up, 47% of suicide attempts occurred among those who reported any recent thoughts of death or self-harm at the sampled visit. Also, 59% of attempts occurred among those reporting thoughts of death or self-harm at the index visit or any visit in the prior year. The number of suicide deaths within 90 days (N=10) was too small to accurately assess the relationship between PHQ-9 item 9 response and subsequent suicide death. CONCLUSIONS: Among outpatients with psychotic disorders, response to item 9 of the PHQ-9 accurately identified those at increased short-term risk of a suicide attempt.
Effects of moringa leaves (Moringa oleifera) extraction on quality changes and melanosis of giant freshwater prawn (Macrobrachium rosenbergii) during chilled storage

An aqueous extraction of moringa (Moringa oleifera) leaves were prepared as the edible coats for keeping the quality of the giant freshwater prawn (Macrobrachium rosenbergii). In addition, the antioxidant properties and activity; total phenolic content (TPC), total flavonoid contents (TFC), free radical scavenging activity (DPPH), and ferric reducing antioxidant power (FRAP) of moringa leaves were also determined. The phenolic compounds and antioxidant properties in the moringa leaves are low; 16.14 mgGAEg-1 for TPC; 5.57 mgQEg-1 for TFC; 1.36 mgTEg-1 for DPPH; and 3.05 mgTEg-1 for FRAP. The experiment was further conducted by coating the M. rosenbergii with moringa leaves extraction before chilled storage at 4°C for 15 days. Moringa leaves extraction were effectively reduced the microflora count in M. rosenbergii (P<0.05). Total volatile basis nitrogen (TVB-N) value showed a significant (P<0.05) lower amount in treated samples compared to the controls. Melanosis were obvious in controls compared to the treated samples. After 15 days of chilled storage, the sensory properties; taste, texture and odour of treated samples were acceptable by the panelists. Biopreservation of moringa leaves extraction significantly benefits in keeping the quality of M. rosenbergii.
Transcatheter aortic valve replacement: relative safety and efficacy of the procedure with different devices

ABSTRACT Introduction: Transcatheter aortic valve replacement (TAVR) is a well-established treatment for patients with severe aortic stenosis and intermediate-to-high surgical risk. The increasing clinical experience along with technical and design iterations of transcatheter valve systems have contributed to reducing adverse events and improving clinical outcomes. Areas covered: Overview of the latest generation transcatheter heart valves (THVs), focusing on early safety and efficacy outcomes. Expert commentary: Improvements in valve repositionability, reducing the size of valve delivery systems, and antiparavalvular leak iterations have contributed to improving the safety and clinical outcomes following TAVR. However, while certain complications like major vascular events and residual paravalvular leaks have significantly decreased with the arrival of newer generation THVs, no major changes in thromboembolic events (particularly stroke) have been observed, whereas other complications like conduction disturbances requiring pacemaker implantation have slightly increased over time. Also, no major progress on device retrievability has been observed in the last years. The expansion of TAVR toward the treatment of younger and lower risk patients, as well as newer indications (e.g. asymptomatic patients) will likely require an extra-effort involving additional device iterations and complementary therapies (e.g. embolic protection, newer vascular closure devices) to further improve safety and clinical outcomes.
HMGB1 gene polymorphism is associated with coronary artery lesions and intravenous immunoglobulin resistance in Kawasaki disease.

Objectives Kawasaki disease (KD) is an acute systemic vasculitis of unknown aetiology that affects infants and young children. Recent reports of elevated serum high mobility group box 1 (HMGB1) level during the acute phase of KD and its relationship to poor response to IVIG treatment suggest a possible association of HMGB1 polymorphisms with KD. We investigated the association between the polymorphisms of the HMGB1 gene, KD susceptibility, coronary artery lesions, and KD response to IVIG treatment. Methods Whole genome sequencing of the HMGB1 gene was performed to identify causative variants. Two tagging single nucleotide polymorphisms of the HMGB1 gene were selected using linkage disequilibrium analysis. The tagging single nucleotide polymorphisms were genotyped using the TaqMan Allelic Discrimination assay in a total of 468 subjects (265 KD patients and 203 controls). Results The HMGB1 single nucleotide polymorphisms were not associated with KD susceptibility. However, in KD patients, there was a significant association of rs1412125 with coronary artery lesions formation in the recessive model (GG vs AA + GA: odds ratio = 4.98, 95% CI = 1.69-14.66, P = 0.005). In addition, rs1412125 was associated with IVIG resistance in the recessive (GG vs AA + GA: odds ratio = 4.11, 95% CI = 1.38-12.23, P = 0.017) and allelic models (G vs A: odds ratio = 1.80, 95% CI = 1.06-3.06, P = 0.027). Conclusion The rs1412125 in HMGB1 might be a risk factor for the development of coronary artery lesions and IVIG resistance in KD patients.
The within-participant Correlation between s-RPE and Heart Rate in Youth Sport

Abstract The monitoring of training load is important to ensure athletes are adapting optimally to a training stimulus. Before quantification of training load can take place, coaches must be confident that the tools available are accurate. We aimed to quantify the within-participant correlation between the session rating of perceived exertion (s-RPE) and summated heart rate zone (sHRz) methods of monitoring internal training load. Training load (s-RPE and heart rate) data were collected for rugby, soccer and field hockey field-based training sessions over a 14-week in-season period. A total of 397 sessions were monitored (rugby n=170, soccer n=114 and field hockey n=113). Within-subject correlations between s-RPE and sHRz were quantified for each sport using a general linear model. Large correlations between s-RPE and the sHRz method were found for rugby (r=0.68; 95% CI 0.59–0.75) and field hockey (r=0.60; 95% CI 0.47–0.71) with a very large correlation found for soccer (r=0.72; 95% CI 0.62–0.80). No significant differences were found between the correlations for each sport. The very large and large correlations found between s-RPE and the sHRz methods support the use of s-RPE in quantifying internal training load in youth sport.
Strategies for Coexistence in Molecular Communication

Some of the most ambitious applications of molecular communications are expected to lie in nanomedicine and advanced manufacturing. In these domains, the molecular communication system is surrounded by a range of biochemical processes, some of which may be sensitive to chemical species used for communication. Under these conditions, the biological system and the molecular communication system impact each other. As such, the problem of coexistence arises, where both the reliability of the molecular communication system and the function of the biological system must be ensured. In this paper, we study this problem with a focus on interactions with biological systems equipped with chemosensing mechanisms, which arises in a large class of biological systems. We motivate the problem by considering chemosensing mechanisms arising in bacteria chemotaxis, a ubiquitous and well-understood class of biological systems. We, then, propose strategies for a molecular communication system to minimize the disruption of biological system equipped with a chemosensing mechanism. This is achieved by exploiting tools from the theory of chemical reaction networks. To investigate the capabilities of our strategies, we obtain fundamental information theoretic limits by establishing a new connection with the problem of covert communications.