Miracle-dz/UniFAR-FTUs huggingface dataset:
When it comes to trials, do we get what we pay for?

Randomized clinical trials supported by government agencies are critical for advancing knowledge about a large number of interventions (e.g., generic therapies, health system strategies, and surgery) that are relevant to clinical practice and public health. There is a need, however, for timely publication of trial results, to allow health care providers to use the information promptly. In this issue of the Journal, Gordon et al.1 report a thought-provoking study of 244 trials funded by the National Heart, Lung, and Blood Institute. Although data collection for these trials was completed between January 1, 2000, and December 31, 2011, the results of .
Bioavailability of vitamin D and its metabolites in black and white adults.

Vitamin D deficiency has become a global health problem that has been associated not only with metabolic bone disease but also with many chronic illnesses.1 The definition of vitamin D deficiency has been controversial, in part owing to the interpretation of surrogates associated with vitamin D status. The Institute of Medicine concluded that to maximize bone health, the level of 25-hydroxyvitamin D should be higher than 20 ng per milliliter.2 Others have relied on parathyroid hormone levels to assess vitamin D status, arguing that such levels reach a nadir and plateau when 25-hydroxyvitamin D levels are 30 to 40 ng .
Initiation of dapagliflozin and treatment‐emergent fractures

An increase in fracture risk has been reported in patients with type 2 diabetes mellitus (T2DM) treated with canagliflozin, possibly mediated by effects induced by all members of the sodium‐glucose co‐transporter‐2 (SGLT2) inhibitor class. It is unclear whether initiation of dapagliflozin is followed by an increase in the risk of fracture; therefore, we performed a population‐based, open cohort study (from January 2013 to January 2016) using The Health Improvement Network (THIN). A total of 22 618 people with T2DM (4548 exposed to dapagliflozin and 18 070 receiving standard antidiabetic treatment, matched for age, sex, body mass index and diabetes duration) with no history of fractures at baseline were included. The primary outcome was the occurrence of any fragility fracture (hip, spine, wrist) during the observation period. Risk of any fracture served as a secondary outcome. Adjusted hazard rate ratios (HRs) with 95% confidence intervals (CIs) were calculated using Cox regression. A total of 289 fractures (132 fragility fractures) were recorded. No difference in the risk of fragility fracture was detected between participants prescribed dapagliflozin and matched control participants (crude HR 0.90, 95% CI 0.59‐1.39, P = .645; adjusted HR 0.87, 95% CI 0.56‐1.35, P = .531). Similarly, no difference in the risk of any fracture was detected (adjusted HR 0.89, 95% CI 0.66‐1.20; P = .427). Sensitivity analyses limited to the subset of the population at high risk of fracture produced similar results; thus, there was no evidence to suggest an increase in the risk of treatment‐emergent fractures in patients with T2DM who initiated treatment with dapagliflozin.
Bevacizumab in glioblastoma--still much to learn.

Glioblastoma, which remains one of the most lethal tumors, is associated with a median survival of only approximately 15 months, despite aggressive combination therapy. Interest in therapeutic targeting of the florid angiogenesis characteristic of glioblastoma led to several phase 2 trials of bevacizumab, a humanized monoclonal antibody targeted against vascular endothelial growth factor (VEGF), in patients with recurrent glioblastoma.1–3 These early trials showed dramatic and unprecedented responses on magnetic resonance imaging (MRI) (and, occasionally, clinical responses) among patients with a recurrent tumor for which no effective treatment existed, thereby leading to approval of bevacizumab by the Food and Drug .
Erratum: Effect of GLP‐1 receptor agonist treatment on body weight in obese antipsychotic‐treated patients with schizophrenia: A randomized, placebo‐controlled trial

Aims Schizophrenia is associated with cardiovascular co-morbidity and a reduced life-expectancy of up to 20 years. Antipsychotics are dopamine D2 receptor antagonists and the standard of medical care in schizophrenia, but the drugs are associated with severe metabolic side effects like obesity and diabetes. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are registered for treatment of both obesity and type 2 diabetes. We investigated metabolic effects of the GLP-1RA, exenatide once-weekly, in non-diabetic, antipsychotic-treated, obese patients with schizophrenia. Material and Methods Antipsychotic-treated, obese, non-diabetic, schizophrenia spectrum patients were randomized to double-blinded adjunctive treatment with once-weekly subcutaneous exenatide (n = 23) or placebo (n = 22) injections for three months. The primary outcome was body weight loss after treatment and repeated measures analysis of variance was used as statistical analysis. Results Between March 2013 and June 2015, 40 patients completed the trial. At baseline, the mean body weight was 118.3 ± 16.0 kg in the exenatide group and 111.7 ± 18.0 kg in the placebo group, with no group differences (P = 0.23). The exenatide and placebo groups experienced significant (P = 0.004), however, similar (P = 0.98) weight losses of 2.24 ± 3.3 kg and 2.23 ± 4.4 kg, respectively, after three months of treatment. Conclusions Treatment with exenatide once-weekly did not promote weight loss in obese, antipsychotic-treated patients with schizophrenia compared to placebo. Our results could suggest that the body weight-lowering effect of GLP-1RAs involves dopaminergic signaling, but blockade of other receptor systems may also play a role. Nevertheless, anti-obesity regimens effective in the general population may not be readily implemented in antipsychotic-treated patients with schizophrenia ClinicalTrials.gov identifier: NCT01794429
Determining the optimal dose of atrasentan by evaluating the exposure‐response relationships of albuminuria and bodyweight

This study aimed to identify the optimal dose of the endothelin‐1 receptor antagonist atrasentan with maximal albuminuria reduction and minimal signs of sodium retention, as manifested by increase in bodyweight. Data from the RADAR‐JAPAN studies were used, evaluating the effect of 0.75 or 1.25 mg/d of atrasentan in 161 patients with type 2 diabetes and kidney disease. Individual pharmacokinetic parameters were estimated using a population pharmacokinetic approach. Subsequently, changes in the urinary albumin‐to‐creatinine ratio (UACR) and bodyweight from baseline after 2 weeks' exposure were modelled as a function of the pharmacokinetic parameters. The 0.75 and 1.25 mg doses showed a mean UACR reduction of 34.0% and 40.1%, whereas mean bodyweight increased by 0.9 and 1.1 kg, respectively. A large variation between individuals was observed in the UACR and bodyweight responses. Individual pharmacokinetic parameters correlated significantly with both individual UACR and bodyweight responses (P < .01). The individual response curves for UACR and bodyweight crossed at approximately the mean trough concentration of 0.75 mg atrasentan, indicating that 0.75 mg/d of atrasentan is the optimal dose for kidney protection with maximal efficacy (albuminuria reduction) and safety (minimal sodium retention).
Video Laryngoscopy vs Direct Laryngoscopy on Successful First-Pass Orotracheal Intubation Among ICU Patients: A Randomized Clinical Trial

Importance In the intensive care unit (ICU), orotracheal intubation can be associated with increased risk of complications because the patient may be acutely unstable, requiring prompt intervention, often by a practitioner with nonexpert skills. Video laryngoscopy may decrease this risk by improving glottis visualization. Objective To determine whether video laryngoscopy increases the frequency of successful first-pass orotracheal intubation compared with direct laryngoscopy in ICU patients. Design, Setting, and Participants Randomized clinical trial of 371 adults requiring intubation while being treated at 7 ICUs in France between May 2015 and January 2016; there was 28 days of follow-up. Interventions Intubation using a video laryngoscope (n = 186) or direct laryngoscopy (n = 185). All patients received general anesthesia. Main Outcomes and Measures The primary outcome was the proportion of patients with successful first-pass intubation. The secondary outcomes included time to successful intubation and mild to moderate and severe life-threatening complications. Results Among 371 randomized patients (mean [SD] age, 62.8 [15.8] years; 136 [36.7%] women), 371 completed the trial. The proportion of patients with successful first-pass intubation did not differ significantly between the video laryngoscopy and direct laryngoscopy groups (67.7% vs 70.3%; absolute difference, −2.5% [95% CI, −11.9% to 6.9%]; P = .60). The proportion of first-attempt intubations performed by nonexperts (primarily residents, n = 290) did not differ between the groups (84.4% with video laryngoscopy vs 83.2% with direct laryngoscopy; absolute difference 1.2% [95% CI, −6.3% to 8.6%]; P = .76). The median time to successful intubation was 3 minutes (range, 2 to 4 minutes) for both video laryngoscopy and direct laryngoscopy (absolute difference, 0 [95% CI, 0 to 0]; P = .95). Video laryngoscopy was not associated with life-threatening complications (24/180 [13.3%] vs 17/179 [9.5%] for direct laryngoscopy; absolute difference, 3.8% [95% CI, −2.7% to 10.4%]; P = .25). In post hoc analysis, video laryngoscopy was associated with severe life-threatening complications (17/179 [9.5%] vs 5/179 [2.8%] for direct laryngoscopy; absolute difference, 6.7% [95% CI, 1.8% to 11.6%]; P = .01) but not with mild to moderate life-threatening complications (10/181 [5.4%] vs 14/181 [7.7%]; absolute difference, −2.3% [95% CI, −7.4% to 2.8%]; P = .37). Conclusions and Relevance Among patients in the ICU requiring intubation, video laryngoscopy compared with direct laryngoscopy did not improve first-pass orotracheal intubation rates and was associated with higher rates of severe life-threatening complications. Further studies are needed to assess the comparative effectiveness of these 2 strategies in different clinical settings and among operators with diverse skill levels. Trial Registration clinicaltrials.gov Identifier: NCT02413723
Gene Expression Variation Resolves Species and Individual Strains among Coral-Associated Dinoflagellates within the Genus Symbiodinium

Reef-building corals depend on symbiotic mutualisms with photosynthetic dinoflagellates in the genus Symbiodinium. This large microalgal group comprises many highly divergent lineages (“Clades A–I”) and hundreds of undescribed species. Given their ecological importance, efforts have turned to genomic approaches to characterize the functional ecology of Symbiodinium. To date, investigators have only compared gene expression between representatives from separate clades—the equivalent of contrasting genera or families in other dinoflagellate groups—making it impossible to distinguish between clade-level and species-level functional differences. Here, we examined the transcriptomes of four species within one Symbiodinium clade (Clade B) at ∼20,000 orthologous genes, as well as multiple isoclonal cell lines within species (i.e., cultured strains). These species span two major adaptive radiations within Clade B, each encompassing both host-specialized and ecologically cryptic taxa. Species-specific expression differences were consistently enriched for photosynthesis-related genes, likely reflecting selection pressures driving niche diversification. Transcriptional variation among strains involved fatty acid metabolism and biosynthesis pathways. Such differences among individuals are potentially a major source of physiological variation, contributing to the functional diversity of coral holobionts composed of unique host–symbiont genotype pairings. Our findings expand the genomic resources available for this important symbiont group and emphasize the power of comparative transcriptomics as a method for studying speciation processes and interindividual variation in nonmodel organisms.
Parallel Mitogenome Sequencing Alleviates Random Rooting Effect in Phylogeography

Reliably rooted phylogenetic trees play irreplaceable roles in clarifying diversification in the patterns of species and populations. However, such trees are often unavailable in phylogeographic studies, particularly when the focus is on rapidly expanded populations that exhibit star-like trees. A fundamental bottleneck is known as the random rooting effect, where a distant outgroup tends to root an unrooted tree “randomly. ” We investigated whether parallel mitochondrial genome (mitogenome) sequencing alleviates this effect in phylogeography using a case study on the Sea of Japan lineage of the intertidal goby Chaenogobius annularis. Eighty-three C. annularis individuals were collected and their mitogenomes were determined by high-throughput and low-cost parallel sequencing. Phylogenetic analysis of these mitogenome sequences was conducted to root the Sea of Japan lineage, which has a star-like phylogeny and had not been reliably rooted. The topologies of the bootstrap trees were investigated to determine whether the use of mitogenomes alleviated the random rooting effect. The mitogenome data successfully rooted the Sea of Japan lineage by alleviating the effect, which hindered phylogenetic analysis that used specific gene sequences. The reliable rooting of the lineage led to the discovery of a novel, northern lineage that expanded during an interglacial period with high bootstrap support. Furthermore, the finding of this lineage suggested the existence of additional glacial refugia and provided a new recent calibration point that revised the divergence time estimation between the Sea of Japan and Pacific Ocean lineages. This study illustrates the effectiveness of parallel mitogenome sequencing for solving the random rooting problem in phylogeographic studies.
Efficacy and safety of sitagliptin added to treatment of patients with type 2 diabetes inadequately controlled with premixed insulin

To improve understanding of the safety and efficacy of adding sitagliptin to treatment of patients with type 2 diabetes taking premixed insulin, data from patients using premixed insulin ± metformin (screening HbA1c ≥7.5% and ≤11%) in either of two clinical trials in which sitagliptin 100 mg once‐daily or placebo was added to various formulations of insulin treatment, were analysed. In both trials, insulin doses were to remain stable throughout the 24‐week trial period. At week 24, the between‐group difference (sitagliptin ‐ placebo) in the least squares mean (95% confidence intervals) change from baseline in HbA1c in patients using premixed insulin was −0.43% (−0.58, −0.28), P <0.001. Adverse events were generally similar between the treatment groups. The incidence of symptomatic hypoglycaemia was slightly higher with sitagliptin, and the incidence of hypoglycaemia requiring medical attention was slightly higher with placebo; in both cases the difference was not statistically significant. The data from this pooled analysis confirm the utility of sitagliptin used in combination with premixed insulin in patients with type 2 diabetes.
Allele-Specific Expression Analysis Does Not Support Sex Chromosome Inactivation on the Chicken Z Chromosome

Heterogametic sex chromosomes have evolved many times independently, and in many cases, the loss of functional genes from the sex-limited Y or W chromosome leaves only one functional gene copy on the corresponding X or Z chromosome in the heterogametic sex. Because gene dose often correlates with gene expression level, this difference in gene dose between males and females for X- or Z-linked genes in some cases has selected for chromosome-wide transcriptional dosage compensation mechanisms to counteract any reduction in expression in the heterogametic sex. These mechanisms are thought to restore the balance between sex-linked loci and the autosomal genes they interact with, and this also typically results in equal expression between the sexes. However, dosage compensation in many other species is incomplete, and in the case of birds average expression from males (ZZ) remains higher than in females (ZW). Interestingly, recent reports in chickens and related species have shown that the Z chromosome is expressed less in males than would be expected from two copies of the chromosome, and recent data from cell-based approaches on 11 loci in chicken have suggested that one Z chromosome is partially inactivated in males, in a mechanism thought to be homologous to X inactivation in therian mammals. In the present study, we use controlled crosses in three tissues to test for the presence of Z inactivation in males, which would be expected to bias transcription to the active gene copy (allele-specific expression). We show that for the vast majority of genes on the chicken Z chromosome, males express both parental alleles at statistically similar levels, indicating no Z chromosome inactivation. For those Z chromosome loci with detectable ASE in males, we show that the most likely cause is cis-regulatory variation, rather than Z chromosome inactivation. Taken together, our results indicate that unlike the X chromosome in mammals, Z inactivation does not affect an appreciable number of loci in chicken.
A implementação da sistematização da assistência de enfermagem no serviço de saúde hospitalar do Brasil

This is a bibliographical study aimed at analyzing the implantation of Nursing Assistance Systematization in Brazilian hospital health care services from 1986 to 2005. The LILACS, BDENF, and SciELO databases were used as information sources. Thirty articles were included (15 records of experience, 14 field investigations, and one theoretical reflection), having as a criteria the implementation of Nursing Assistance Systematization in Brazil, in the hospital area. The content analysis revealed thematic modality. Through article analysis it is noted that the aim of systematization implantation is to organize care by means of adopting of a systematic method, thus providing the nurse (re)definition of his/her action. The administrative theoretical reference choice and strategies usedare reflected in working conditions and on the manner of acting, with interference in the implantation process. DESCRIPTORS: Management. Nursing. Nursing care. Hospital care.
Pulmonary Manifestations in Mixed Connective Tissue Disease

For many years, physicians have observed that some patients exhibit features of more than one rheumatologic disease and thus do not fit into the traditional classification. Complicating this clinical aspect is the fact that laboratory test results for even the well-established rheumatologic entities are occasionally helpful but not pathognomonic and must be correlated with the clinical picture for establishing the correct diagnosis. The diagnoses of systemic lupus erythematosus (SLE), progressive systemic sclerosis (PSS), polymyositis (PM), and rheumatoid arthritis (RA) depend more on the history, clinical findings, and pattern of organ involvement than on serologic tests, which lack specificity. In the past, patients demonstrating features of more than one of these diseases were classified under the terms, "overlap syndrome," "undifferentiated connective tissue disease," "sclerodermatomyositis," " R U P U S " (RA and SLE), or "lupoderma" (SLE and PSS). ,2 In 1972, Sharp and colleagues recognized that many patients with clinical features of SLE, PSS, and PM had unusually high titers of a specific circulating antibody to an extractable nuclear ribonucleoprotein antigen (ENA) and introduced the term "mixed connective tissue disease" (MCTD) to describe the entity. The presence of high titers of antibody to ENA and the absence of antibodies to Sm antigen are thought to be specific for MCTD, although this inference has been questioned. Studies using T lymphocytes have inferred that M C T D may indeed be a distinct entity. Although the debate continues on whether M C T D should be considered a distinct entity, ,5 -14 the literature search reveals not only many new articles on this topic, but also that more and more clinicians are accepting the diagnosis of M C T D . It appears that the entity " M C T D " (also recently described as "Sharp's syndrome") has found its niche and is here to stay. The etiology and prevalence of M C T D is unknown, but it is believed to be more common than PM but less common than SLE. The majority of patients are female, and the average age at the time of diagnosis is 37 years; no unusual ethnic or racial preponderance has been noted. Early observations of M C T D inferred infrequent renal disease, a prolonged and benign course, and excellent response to nonsteroidal anti-inflammatory agents and corticosteroids. However, subsequent studies revealed that renal disease occurs in 10 to 20% and that some patients may require aggressive or prolonged pharmacologic therapy.
Changes in cognitive function in a randomized trial of physical activity: results of the lifestyle interventions and independence for elders pilot study.

BACKGROUND Cognitive impairment is an important contributor to disability. Limited clinical trial evidence exists regarding the impact of physical exercise on cognitive function (CF). We report results of a pilot study to provide estimates of the relative impact of physical activity (PA) on 1-year changes in cognitive outcomes and to characterize relationships between changes in mobility disability and changes in cognition in older adults at increased risk for disability. METHODS Sedentary persons (102) at increased risk for disability (aged 70-89 years) were randomized to moderate-intensity PA or health education. Participants were administered the Digit Symbol Substitution Test (DSST), Rey Auditory Verbal Learning Test (RAVLT), modified Stroop test, and Modified Mini-Mental State Examination at baseline and 1 year. RESULTS Group differences were not significant but improvements in cognitive scores were associated with improvements in physical function. Specifically, the DSST significantly correlated with change in the Short Physical Performance Battery score (r = .38, p = .0002), in chair stand score (r = .26, p = .012), in balance score (r = .21, p = .046), and in 400-m gait speed (r = .15, p = .147). Change recall on the RAVLT and in the Stroop test was also positively correlated with changes in chair stand and balance, respectively. CONCLUSIONS These results provide further support for the benefits of exercise on CF in older adults. An adequately powered clinical trial of PA involving older adults at increased risk for cognitive disability is needed to expand the indications for prescribing exercise for prevention of decline in brain function.