Miracle-dz/UniFAR-FTUs huggingface dataset:
Caffeine and Progression of Parkinson Disease: A Deleterious Interaction With Creatine

ObjectiveIncreased caffeine intake is associated with a lower risk of Parkinson disease (PD) and is neuroprotective in mouse models of PD. However, in a previous study, an exploratory analysis suggested that, in patients taking creatine, caffeine intake was associated with a faster rate of progression. In the current study, we investigated the association of caffeine with the rate of progression of PD and the interaction of this association with creatine intake. MethodsData were analyzed from a large phase 3 placebo-controlled clinical study of creatine as a potentially disease-modifying agent in PD. Subjects were recruited for this study from 45 movement disorders centers across the United States and Canada. A total of 1741 subjects with PD participated in the primary clinical study, and caffeine intake data were available for 1549 of these subjects. The association of caffeine intake with rate of progression of PD as measured by the change in the total Unified Parkinson Disease Rating Scale score and the interaction of this association with creatine intake were assessed. ResultsCaffeine intake was not associated with the rate of progression of PD in the main analysis, but higher caffeine intake was associated with significantly faster progression among subjects taking creatine. ConclusionsThis is the largest and longest study conducted to date that addresses the association of caffeine with the rate of progression of PD. These data indicate a potentially deleterious interaction between caffeine and creatine with respect to the rate of progression of PD.
Developing Deep Learning Applications for Life Science and Pharma Industry

Abstract Deep Learning has boosted artificial intelligence over the past 5 years and is seen now as one of the major technological innovation areas, predicted to replace lots of repetitive, but complex tasks of human labor within the next decade. It is also expected to be ‘game changing’ for research activities in pharma and life sciences, where large sets of similar yet complex data samples are systematically analyzed. Deep learning is currently conquering formerly expert domains especially in areas requiring perception, previously not amenable to standard machine learning. A typical example is the automated analysis of images which are typically produced en-masse in many domains, e. g. , in high-content screening or digital pathology. Deep learning enables to create competitive applications in so-far defined core domains of ‘human intelligence’. Applications of artificial intelligence have been enabled in recent years by (i) the massive availability of data samples, collected in pharma driven drug programs (=‘big data’) as well as (ii) deep learning algorithmic advancements and (iii) increase in compute power. Such applications are based on software frameworks with specific strengths and weaknesses. Here, we introduce typical applications and underlying frameworks for deep learning with a set of practical criteria for developing production ready solutions in life science and pharma research. Based on our own experience in successfully developing deep learning applications we provide suggestions and a baseline for selecting the most suited frameworks for a future-proof and cost-effective development.
Survival of very preterm infants: Epipage, a population based cohort study

Objective: To evaluate the outcome for all infants born before 33 weeks gestation until discharge from hospital. Design: A prospective observational population based study. Setting: Nine regions of France in 1997. Patients: All births or late terminations of pregnancy for fetal or maternal reasons between 22 and 32 weeks gestation. Main outcome measure: Life status: stillbirth, live birth, death in delivery room, death in intensive care, decision to limit intensive care, survival to discharge. Results: A total of 722 late terminations, 772 stillbirths, and 2901 live births were recorded. The incidence of very preterm births was 1.3 per 100 live births and stillbirths. The survival rate for births between 22 and 32 weeks was 67% of all births (including stillbirths), 85% of live births, and 89% of infants admitted to neonatal intensive care units. Survival increased with gestational age: 31% of all infants born alive at 24 weeks survived to discharge, 78% at 28 weeks, and 97% at 32 weeks. Survival among live births was lower for small for gestational age infants, multiple births, and boys. Overall, 50% of deaths after birth followed decisions to withhold or withdraw intensive care: 66% of deaths in the delivery room, decreasing with increasing gestational age; 44% of deaths in the neonatal intensive care unit, with little variation with gestational age. Conclusion: Among very preterm babies, chances of survival varies greatly according to the length of gestation. At all gestational ages, a large proportion of deaths are associated with a decision to limit intensive care.
An efficiency multiuser diversity scheme with partial feedback on common uplink channel

In the multiple antenna multiuser systems, multiuser diversity technique is a simple but practical technique to increase system throughput, especially when many users exist. This, however, may cost too much radio resource for the feedback request of channel quality metrics for each user in every slot. By investigating the throughput performance of multiuser diversity system with random beamforming in the downlink broadcast channel, this paper proposes an efficient scheme with partial feedback of channel metric on the common uplink channel. The uplink feedback channel is sliced into many parallel orthogonal sub-channels and for every feedback sub-channel, a contention-based multiple access approach is used among all the users. Performance analysis proves that with the proper threshold setting for distinguishing a "good" channel, the system under the proposed scheme can pay much less for uplink feedback channel with little loss of system throughput, which is also means that the system could accommodate more users within given radio bandwidth of uplink channel.
Antioxidant defense in children with chronic viral hepatitis B and C.

INTRODUCTION The aim of the study was estimation of antioxidant defence state in children with chronic viral hepatitis. MATERIAL AND METHODS We examined 100 children with chronic viral hepatitis who have serological and molecular markers of HBV or HCV infection. In all patients catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities in erythrocytes were assayed. RESULTS We observed statistically significant decrease of CAT and SOD activities and increase of GSH-Px activity in children with chronic hepatitis B and C. CONCLUSIONS Our data suggest the possibility of insufficiency of antioxidant barrier in children with chronic viral hepatitis.
Melatonin ameliorates high fat diet‐induced diabetes and stimulates glycogen synthesis via a PKCζ‐Akt‐GSK3β pathway in hepatic cells

Abstract: Low levels of melatonin in circulation had been reported to be related to the development of diabetes. Melatonin administration in animals increases hepatic glycogen content to lower blood glucose. However, the signaling pathway for these effects is still unclear. The present study shows that intraperitoneal injection of 10 mg/kg melatonin ameliorated glucose utilization and insulin sensitivity in high fat diet‐induced diabetic mice with an increase in hepatic glycogen and improvement in liver steatosis. We used HepG2 cells to investigate the signaling pathways for the melatonin‐stimulated hepatic glycogen increment. Treatment of HepG2 cells with 1 nm melatonin markedly increased glycogen synthesis which was blocked by the melatonin receptor antagonist luzindole. In addition, melatonin increased the phosphorylation of subcellular signals at the level of protein kinase C ζ (PKCζ), Akt, and glycogen synthase kinase 3β (GSK3β) while the increase in glycogen synthesis induced by melatonin was inhibited by PKCζ pseudo‐peptide. However, 3′,5′‐cyclic adenosine monophosphate‐activated protein kinase (AMPK) was not influenced by melatonin treatment. Taken together, melatonin improves glucose intolerance and insulin resistance in high fat diet‐induced diabetic mice and stimulates glycogen synthesis via a PKCζ‐Akt‐GSK3β pathway in HepG2 cells.
A digital photographic measurement method for quantifying foot posture: validity, reliability, and descriptive data.

CONTEXT Although abnormal foot posture long has been associated with lower extremity injury risk, the evidence is equivocal. Poor intertester reliability of traditional foot measures might contribute to the inconsistency. OBJECTIVES To investigate the validity and reliability of a digital photographic measurement method (DPMM) technology, the reliability of DPMM-quantified foot measures, and the concurrent validity of the DPMM with clinical-measurement methods (CMMs) and to report descriptive data for DPMM measures with moderate to high intratester and intertester reliability. DESIGN Descriptive laboratory study. SETTING Biomechanics research laboratory. PATIENTS OR OTHER PARTICIPANTS A total of 159 people participated in 3 groups. Twenty-eight people (11 men, 17 women; age = 25 ± 5 years, height = 1.71 ± 0.10 m, mass = 77.6 ± 17.3 kg) were recruited for investigation of intratester and intertester reliability of the DPMM technology; 20 (10 men, 10 women; age = 24 ± 2 years, height = 1.71 ± 0.09 m, mass = 76 ± 16 kg) for investigation of DPMM and CMM reliability and concurrent validity; and 111 (42 men, 69 women; age = 22.8 ± 4.7 years, height = 168.5 ± 10.4 cm, mass = 69.8 ± 13.3 kg) for development of a descriptive data set of the DPMM foot measurements with moderate to high intratester and intertester reliabilities. INTERVENTION(S) The dimensions of 10 model rectangles and the 28 participants' feet were measured, and DPMM foot posture was measured in the 111 participants. Two clinicians assessed the DPMM and CMM foot measures of the 20 participants. MAIN OUTCOME MEASURE(S) Validity and reliability were evaluated using mean absolute and percentage errors and intraclass correlation coefficients. Descriptive data were computed from the DPMM foot posture measures. RESULTS The DPMM technology intratester and intertester reliability intraclass correlation coefficients were 1.0 for each tester and variable. Mean absolute errors were equal to or less than 0.2 mm for the bottom and right-side variables and 0.1° for the calculated angle variable. Mean percentage errors between the DPMM and criterion reference values were equal to or less than 0.4%. Intratester and intertester reliabilities of DPMM-computed structural measures of arch and navicular indices were moderate to high (>0.78), and concurrent validity was moderate to strong. CONCLUSIONS The DPMM is a valid and reliable clinical and research tool for quantifying foot structure. The DPMM and the descriptive data might be used to define groups in future studies in which the relationship between foot posture and function or injury risk is investigated.
Convolutional Phase Retrieval via Gradient Descent

We study the convolutional phase retrieval problem, of recovering an unknown signal <inline-formula> <tex-math notation="LaTeX">$x \in \mathbb C^{n} $ </tex-math></inline-formula> from <inline-formula> <tex-math notation="LaTeX">$m$ </tex-math></inline-formula> measurements consisting of the magnitude of its cyclic convolution with a given kernel <inline-formula> <tex-math notation="LaTeX">$a \in \mathbb C^{m} $ </tex-math></inline-formula>. This model is motivated by applications such as channel estimation, optics, and underwater acoustic communication, where the signal of interest is acted on by a given channel/filter, and phase information is difficult or impossible to acquire. We show that when <inline-formula> <tex-math notation="LaTeX">$a$ </tex-math></inline-formula> is random and the number of observations <inline-formula> <tex-math notation="LaTeX">$m$ </tex-math></inline-formula> is sufficiently large, with high probability <inline-formula> <tex-math notation="LaTeX">$x$ </tex-math></inline-formula> can be efficiently recovered up to a global phase shift using a combination of spectral initialization and generalized gradient descent. The main challenge is coping with dependencies in the measurement operator. We overcome this challenge by using ideas from decoupling theory, suprema of chaos processes and the restricted isometry property of random circulant matrices, and recent analysis of alternating minimization methods.
Abl promotes cadherin-dependent adhesion and signaling in myoblasts

Cell-cell contact promotes myogenic differentiation but the mechanisms that regulate this phenomenon are not well understood. Cdo (also known as Cdon), an Ig superfamily member, functions as a component of cell surface complexes to promote myogenic differentiation through activation of p38a/b MAP kinase. We recently showed that N-cadherin ligation activated p38a/b in a Cdo-dependent manner, whereas N-cadherin ligation-dependent activation of ERK MAP kinase was not affected by loss of Cdo. The non-receptor tyrosine kinase Abl associates with Cdo during myoblast differentiation and is necessary for full activition of p38a/b during this process. The Abl SH3 domain binds to a PxxP motif in the Cdo intracellular domain, and both these motifs are required for their promyogenic activity. Here we show that Abl is necessary for p38a/b activation initiated by N-cadherin ligation, but in contrast to Cdo, Abl is also required for N-cadherin-dependent ERK activation. Moreover, Abl is required for efficient cadherin-mediated myoblast aggregation via modulation of RhoA-ROCK signaling. Therefore, Abl regulates N-cadherin-mediated p38a/b activation by multiple mechanisms, more generally through regulation of cell-cell adhesion and specifically as a component of Cdo-containing complexes. The role of Cdo as a multifunctional coreceptor with roles in several pathways is also discussed.
Transcription by RNA polymerase I stimulates mitotic recombination in Saccharomyces cerevisiae

The recombination-stimulating sequence HOT1 is derived from the ribosomal DNA array of Saccharomyces cerevisiae and corresponds to sequences that promote transcription by RNA polymerase I. When inserted at a chromosomal location outside the ribosomal DNA array, HOT1 stimulates mitotic recombination in the adjacent sequences. To investigate the relationship between transcription and recombination, transcription promoted by HOT1 was directly examined. These studies demonstrated that transcription starts at the RNA polymerase I initiation site in HOT1 and proceeds through the chromosomal sequences in which recombination is enhanced. Linker insertion mutations in HOT1 were generated and assayed for recombination stimulation and for promoter function; this analysis demonstrated that the same sequences are required for both activities. These results indicate that the ability of HOT1 to enhance recombination is related to, and most likely dependent on, its ability to promote transcription.
A kinase subunit of the human mediator complex, CDK8, positively regulates transcriptional activation

The human thyroid hormone receptor‐associated proteins (TRAP)/Mediator and related complexes mediate transcription through regulatory factors. To further understand the structural and functional diversity of these complexes we established three HeLa cell lines each expressing one of three epitope‐tagged human TRAP/Mediator subunits, MED6, MED7, and CDK8 and isolated the complexes in which these subunits were contained by affinity and HPLC‐gel filtration chromatography. The largest complexes from each cell line had a molecular mass of 1.5 MDa and possessed almost identical subunit compositions; we designated these complexes TRAP/Mediator‐like complex 1 (TMLC1). Two potential subcomplexes were additionally observed: a 1‐MDa complex from the CDK8‐cell line (TMLC2) and a 600‐kDa complex from the MED6‐cell line (TMLC3). All three complexes regulated transcription in vitro; TMLC1 and TMLC3 augmented transcriptional activation, whereas TMLC2 repressed it. TMLC1 and TMLC2 phosphorylated RNA polymerase II (Pol II), but TMLC3 did not. Furthermore, TMLC1 predominantly interacted with the general transcription factors TFIIE, TFIIF, and TFIIH, which function during transcription initiation and the transition to elongation. In a final experiment, knockdown of CDK8 using RNA interference prevented transcriptional activation by Gal4‐VP16 in a luciferase‐assay. This, together with the effect of TMLC1 on transcription in vitro, suggests that CDK8 play positive roles in transcriptional activation.
Double-Blind Placebo-Controlled Pilot Study of Sertraline in Military Veterans With Posttraumatic Stress Disorder

The efficacy of sertraline in the treatment of civilian posttraumatic stress disorder (PTSD) has been established by two large placebo-controlled trials. The purpose of the current pilot study was to obtain preliminary evidence of the efficacy of sertraline in military veterans suffering from PTSD. Outpatient Israeli military veterans with a DSM-III-R diagnosis of PTSD were randomized to 10 weeks of double-blind treatment with sertraline (50–200 mg/day; N = 23, 83% male, mean age = 41 years) or placebo (N = 19, 95% male, mean age = 38 years). Efficacy was evaluated by the Clinician-Administered PTSD Scale (CAPS-2) and by Clinical Global Impression Scale-Severity (CGI-S) and -Improvement (CGI-I) ratings. Consensus responder criteria consisted of a 30% or greater reduction in the CAPS-2 total severity score and a CGI-I rating of “much” or “very much” improved. The baseline CAPS-2 total severity score was 94.3 ± 12.9 for sertraline patients, which is notably higher than that reported for most studies of civilian PTSD. On an intent-to-treat endpoint analysis, sertraline showed a numeric but not statistically significant advantage compared with placebo on the CAPS-2 total severity and symptom cluster scores. In the study completer analysis, the mean CGI-I score was 2.4 ± 0.3 for sertraline and 3.4 ± 0.3 for placebo (t = 2.55, df = 30, p = 0.016), CGI-I responder rates were 53% for sertraline and 20% for placebo (χ2 = 3.62, df = 1, p = 0.057), and combined CGI-I and CAPS-2 responder rates (≥30% reduction in baseline CAPS-2 score) were 41% for sertraline and 20% for placebo (χ2 = 1.39, df = 1, p = 0.238). Sertraline treatment was well tolerated, with a 13% discontinuation rate as a result of adverse events. This pilot study suggests that sertraline may be an effective treatment in patients with predominantly combat-induced PTSD, although the effect size seems to be somewhat smaller than what has been reported in civilian PTSD studies. Adequately powered studies are needed to confirm these results and to assess whether continued treatment maintains or further improves response.
Screening and evaluation of candidate trees for terrestrial carbon storage in regions with high air pollution and water stress

ABSTRACT Terrestrial carbon storage is one of many different ways to tackle the problem of greenhouse gases (GHG) emissions resulting from non-point sources. However, the development of large-scale urban forest acreage is not an easy undertaking, and will require significant resources. The systematic screening of candidate tree species and preliminary estimations of their atmospheric carbon removal potential can help stakeholders and policymakers devise site-specific strategies for developing and maintaining sustainable urban forest acreage. This study is focused on finding native candidate trees that are drought-resistant, and could continue to store (sequester) atmospheric carbon in significant quantities over an extended period (> 100 years). In the study, seven urban tree species were identified as the top candidates for terrestrial carbon storage in water-stressed Californian regions, which are also the regions with the worst air quality in the nation. Although the present study is focused on particular water-stressed and air-polluted regions of California, the methodology and strategies presented may serve as a starting point for launching site-specific scoping studies to evaluate the terrestrial carbon storage potential of future urban forest projects in other parts of the world.
Time-course investigation of infection with a low virulent Pasteurella multocida strain in normal and immune-suppressed 12-week-old free-range chickens

Twelve-week-old indigenous chickens, either immune-suppressed using dexamethasone (IS) or non-immune-suppressed (NIS), were challenged with a low virulent strain, Pasteurella multocida strain NCTC 10322T, and developed clinical signs and pathological lesions typical of chronic fowl cholera. NIS birds demonstrated much more severe signs of fowl cholera than IS birds. With few exceptions, signs recorded in IS and NIS birds were of the same types, but significantly milder in the IS birds, indicating that immune suppression does not change the course of infection but rather the severity of signs in fowl cholera. P. multocida signals by fluorescent in situ hybridization (FISH) were observed between 1 h and 14 days in the lungs, trachea, air sacs, liver, spleen, bursa of Fabricius and caecal tonsils, while signals from other organs mostly were observed after 24 h. More organs had FISH signals in NIS birds than in IS birds and at higher frequency per organ. Many organs were positive by FISH even 14 days post infection, and it is suggested that these organs may be likely places for long-term carriage of P. multocida following infection. The present study has demonstrated the spread of P. multocida in different tissues in chickens and distribution of lesions associated with chronic fowl cholera, and pointed to a decrease of pathology in IS birds. Since dexamethasone mostly affects heterophils, the study suggests that these cells play a role in the development of lesions associated with chronic fowl cholera in chickens.
A DC side injected method for improving AC line condition applied in an 18-pulse converter system

In this paper, a new compensation strategy for receiving clean power is proposed with a conventional 18-pulse AC/DC rectifier scheme. In the proposed strategy, the compensation currents are injected at the dc side in front of the inter-phase transformer. The injected currents generated by a three-phase current-controlled inverter effectively improve the total harmonic distortion (THD) of the ac main currents. Compared to the conventional active filters set at the ac side, the three-phase inverter used in the proposed method operates with a rather low kVA rating. Moreover, the 18-pulse AC/DC rectifier draws nearly sinusoidal currents from the ac source under the operation of the proposed compensation strategy. A digital-signal-processor (DSP, TMS320F2812) based digital controller is employed to calculate the desired compensation currents and deals with the trigger signals needed for the three-phase inverter. Simulation of the proposed system is conducted for evaluation and a 1.5kW laboratory prototype is built for test as well. Both the simulated and the experimental results are presented to show the validity of the proposed compensation strategy.
Influence of Helicobacter pylori infection and cetraxate on gastric mucosal blood flow during healing of endoscopic mucosal resection‐induced ulcers

Helicobacter pylori (H. pylori) infection is known to affect the gastric microcirculation, and cetraxate is reported to accelerate gastric ulcer healing, possibly by augmenting gastric mucosal blood flow (MBF). The aim of this study is to clarify the effect of H. pylori infection and cetraxate on MBF during gastric ulcer healing.