Miracle-dz/UniFAR-FTUs huggingface dataset:
Re-Analyzing Phase III Bremelanotide Trials for “Hypoactive Sexual Desire Disorder” in Women

ABSTRACT Kingsberg et al. described results from two 24-week Phase III trials of bremelanotide for treating hypoactive sexual desire disorder (HSDD) in women. 72.72% of protocol-listed outcomes were not reported by Kingsberg et al., who provided results of 15 secondary measures which were not listed in the study protocols. None of their efficacy outcomes were reported in line with CONSORT data reporting standards and no secondary outcome had a stated rationale or cited evidence of validity. My meta-analysis of the trials’ data, based on the FDA New Drug Application, found similar results to Kingsberg et al. However, Kingsberg et al. did not report that a) adverse event-induced study discontinuation was substantially higher on bremelanotide: OR = 11.98, 95% CI = 3.74–38.37, NNH: 6 or b) participants preferred placebo, measured by the combination of both 1) completing a clinical trial and 2) electing to participate in the follow-up open-label study (OR = 0.30, 95% CI = .24-.38, NNH: 4). Bremelanotide’s modest benefits on incompletely reported post-hoc measures of questionable validity in combination with participants substantially preferring to take placebo suggest that the drug is generally not useful. Kingsberg et al.’s data reporting and measurement practices were incomplete and lacked transparency.
A De Novo Transcriptome Assembly of Ceratopteris richardii Provides Insights into the Evolutionary Dynamics of Complex Gene Families in Land Plants

Abstract As the closest extant sister group to seed plants, ferns are an important reference point to study the origin and evolution of plant genes and traits. One bottleneck to the use of ferns in phylogenetic and genetic studies is the fact that genome-level sequence information of this group is limited, due to the extreme genome sizes of most ferns. Ceratopteris richardii (hereafter Ceratopteris) has been widely used as a model system for ferns. In this study, we generated a transcriptome of Ceratopteris, through the de novo assembly of the RNA-seq data from 17 sequencing libraries that are derived from two sexual types of gametophytes and five different sporophyte tissues. The Ceratopteris transcriptome, together with 38 genomes and transcriptomes from other species across the Viridiplantae, were used to uncover the evolutionary dynamics of orthogroups (predicted gene families using OrthoFinder) within the euphyllophytes and identify proteins associated with the major shifts in plant morphology and physiology that occurred in the last common ancestors of euphyllophytes, ferns, and seed plants. Furthermore, this resource was used to identify and classify the GRAS domain transcriptional regulators of many developmental processes in plants. Through the phylogenetic analysis within each of the 15 GRAS orthogroups, we uncovered which GRAS family members are conserved or have diversified in ferns and seed plants. Taken together, the transcriptome database and analyses reported here provide an important platform for exploring the evolution of gene families in land plants and for studying gene function in seed-free vascular plants.
Aflatoxin M1 and ochratoxin A in a human milk bank in the city of São Paulo, Brazil

Because infants are more susceptible to the adverse effects of mycotoxins, this work was carried out to determine aflatoxin M1 (AFM1) and ochratoxin A (OA) in milk from the Human Milk Bank of the Southern Regional Hospital, São Paulo, Brazil. Analytical methods were first established and evaluated. The methods involved the extraction of AFM1 with methanol and OA with 1% aqueous sodium bicarbonate solution and methanol, clean-up with immunoaffinity columns having antibodies specific for each mycotoxin and quantification by high performance liquid chromatography (HPLC) with fluorescence detection. The method established for AFM1 had mean recovery percentages of 94, 77 and 82% and coefficients of variation of 17.5, 3.4 and 4.2% at 0.01, 0.03 and 0.05 ng ml−1, respectively. For the OA method, the corresponding values were 84, 84 and 75% for recovery and 14.1, 3.7 and 4.0% for the coefficient of variation. The limit of quantification for both methods was 0.01 ng ml−1. Of a total of 50 samples analysed, only one was contaminated with AFM1, at 0.024 ng ml−1, and two with OA, at 0.011 and 0.024 ng ml−1. Although the incidence observed was low, it is recommended that the study be extended to other milk banks of the city of São Paulo.
Role of the runt‐related transcription factor (RUNX) family in prostate cancer

Prostate cancer (PCa) is a very complex disease that is a major cause of death in men worldwide. Currently, PCa dependence on the androgen receptor (AR) has resulted in use of AR antagonists and antiandrogen therapies that reduce endogenous steroid hormone production. However, within two to three years of receiving first‐line androgen deprivation therapy, the majority of patients diagnosed with PCa progress to castration‐resistant prostate cancer (CRPC). There is an urgent need for therapies that are more durable than antagonism of the AR axis. Studies of runt‐related transcription factors (RUNX) and their heterodimerization partner, core‐binding factor subunit b (CBFβ), are revealing that the RUNX family are drivers of CRPC. In this review, we describe what is presently understood about RUNX members in PCa, including what regulates and is regulated by RUNX proteins, and the role of RUNX proteins in the tumor microenvironment and AR signaling. We discuss the implications for therapeutically targeting RUNX, the potential for RUNX as PCa biomarkers, and the current pressing questions in the field.
Heartfulness meditation improves loneliness and sleep in physicians and advance practice providers during COVID-19 pandemic

ABSTRACT Objective: Unprecedented work pressures and social isolation during the COVID-19 pandemic may worsen loneliness and sleep problems in health-care professionals. Heartfulness meditation has been shown to improve burnout and sleep. In the current study, the effects of remote Heartfulness meditation in improving loneliness and sleep quality were measured. Methods: Physicians and advance practice providers were randomly assigned to receive either daily Heartfulness Meditation program or no intervention (control group) in a prospective four-week randomized control study design. UCLA loneliness and PSQI scores were collected at baseline and after the program duration of 4 weeks. The study was retrospectively registered with trial Number, ISRCTN85787008 (8 January 2021). Results: Of the 155 subjects enrolled in the study, 50% were lonely and 97% had sleep problems. Attrition rate was 36%. Among those who completed the study, the mean UCLA loneliness scores decreased from 42.1 to 39.4 in the Heartfulness group (N = 40, p = 0.009) and 42.2 to 41.15 in the control group (N = 57, p = 0.254). The mean PSQI scores decreased from 10.75 to 9.14 in the Heartfulness group (N = 41, p = 0.001) and 9.41 to 8.87 in the control group (N = 58, p = 0.122). Younger participants aged 30 and under had higher loneliness and sleep problems. Conclusions: The current study is one of the first attempts to assess loneliness and sleep problems among physicians and advance practice providers during COVID-19 pandemic in the US. A significant burden of loneliness and sleep problems was identified. An improvement of sleep and loneliness was noted with the practice of Heartfulness meditation. This remote intervention might be a useful tool to be explored in larger studies.
The challenge of being slow: Effects of tempo, laterality, and experience on dance movement consistency

Abstract In dance, music, or sports, reproducibility and consistency as well as bilateral dexterity/coordination of movement are crucial for motor control. Research into the biomechanics of movement consistency and variability is important for motor learning to achieve proficiency and maximize outcome reproduction and stability as well as to reduce the risk of injury. Thirty-six participants were instructed to perform a repetitive circular, ipsilateral motion of arms and legs at three different tempi, while being recorded with optical motion capture. Two velocity-based consistency measures were developed an overall measure of consistency and a laterality difference measure. Maintaining velocity consistency was more challenging at slower than at faster tempi, suggesting that slow movement could require more attentional focus and thus become more variable. Music experience resulted in higher consistency, especially on the subdominant body side, possibly due to extensive bilateral training. Outcomes could have potential implications for music instrument, dance, and sports practice and training.
Enzymatic Biosensor Based on Carbon Paste Electrodes Modified with Gold Nanoparticles and Polyphenol Oxidase

The results presented here demonstrate the important catalytic effect of a carbon paste electrode modified by dispersion of gold nanoparticles towards different electroactive compounds. The oxidation of hydrogen peroxide starts at potentials 400 mV less positive than at bare carbon paste, while the reduction, almost negligible at bare carbon paste, starts at 0.100 V. The influence of the size and amount of gold nanoparticles in the composite matrix on the response of the electrode is discussed. The incorporation of albumin within the carbon paste facilitates the dispersion of gold nanoparticles, improving substantially the catalytic effects. At carbon paste modified with gold nanoparticles and albumin, the peak potential separation for hydroquinone decreases from 0.385 V to 0.209 V while the reduction current increases from 16.6 to 75.2 μA. The immobilization of polyphenol oxidase within the carbon paste electrode modified with nanoparticles has allowed us to obtain a very sensitive biosensor for dopamine even in the presence of large excess of ascorbic acid.
Systemic effects of rising atmospheric vapor pressure deficit on plant physiology and productivity

Earth is currently undergoing a global increase in atmospheric vapor pressure deficit (VPD), a trend which is expected to continue as climate warms. This phenomenon has been associated with productivity decreases in ecosystems and yield penalties in crops, with these losses attributed to photosynthetic limitations arising from decreased stomatal conductance. Such VPD increases, however, have occurred over decades, which raises the possibility that stomatal acclimation to VPD plays an important role in determining plant productivity under high VPD. Furthermore, evidence points to more far‐ranging and complex effects of elevated VPD on plant physiology, extending to the anatomical, biochemical, and developmental levels, which could vary substantially across species. Because these complex effects are typically not considered in modeling frameworks, we conducted a quantitative literature review documenting temperature‐independent VPD effects on 112 species and 59 traits and physiological variables, in order to develop an integrated and mechanistic physiological framework. We found that VPD increase reduced yield and primary productivity, an effect that was partially mediated by stomatal acclimation, and also linked with changes in leaf anatomy, nutrient, and hormonal status. The productivity decrease was also associated with negative effects on reproductive development, and changes in architecture and growth rates that could decrease the evaporative surface or minimize embolism risk. Cross‐species quantitative relationships were found between levels of VPD increase and trait responses, and we found differences across plant groups, indicating that future VPD impacts will depend on community assembly and crop functional diversity. Our analysis confirms predictions arising from the hydraulic corollary to Darcy's law, outlines a systemic physiological framework of plant responses to rising VPD, and provides recommendations for future research to better understand and mitigate VPD‐mediated climate change effects on ecosystems and agro‐systems.
Inhibition of astrocyte hemichannel improves recovery from spinal cord injury

Spinal cord injury (SCI) causes severe disability, and the current inability to restore function to the damaged spinal cord leads to lasting detrimental consequences to patients. One strategy to reduce SCI morbidity involves limiting the spread of secondary damage after injury. Previous studies have shown that connexin 43 (Cx43), a gap junction protein richly expressed in spinal cord astrocytes, is a potential mediator of secondary damage. Here, we developed a specific inhibitory antibody, mouse-human chimeric MHC1 antibody (MHC1), that inhibited Cx43 hemichannels, but not gap junctions, and reduced secondary damage in 2 incomplete SCI mouse models. MHC1 inhibited the activation of Cx43 hemichannels in both primary spinal astrocytes and astrocytes in situ. In both SCI mouse models, administration of MHC1 after SCI significantly improved hind limb locomotion function. Remarkably, a single administration of MHC1 30 minutes after injury improved the recovery up to 8 weeks post-SCI. Moreover, MHC1 treatment decreased gliosis and lesion sizes, increased white and gray matter sparing, and improved neuronal survival. Together, these results suggest that inhibition of Cx43 hemichannel function after traumatic SCI reduces secondary damage, limits perilesional gliosis, and improves functional recovery. By targeting hemichannels specifically with an antibody, this study provides a potentially new, innovative therapeutic approach in treating SCI.
Quantification of artifacts during cardiac magnetic resonance in patients with leadless Micra pacemakers

When cardiac magnetic resonance (MR) is performed after previous leadless transcatheter pacemaker implantation, an image distortion has to be expected in the heart region and evaluation of myocardial tissue can be affected. In this clinical prospective study, we aim to assess the extent and impact of this artifact on individual ventricular segments and compare it to conventional pacing devices.
Nanostructured p‐n Junctions for Kinetic‐to‐Electrical Energy Conversion

Piezoelectric ZnO nanorods grown on a flexible substrate are combined with the p‐type semiconducting polymer PEDOT:PSS to produce a p‐n junction device that successfully demonstrates kinetic‐to‐electrical energy conversion. Both the voltage and current output of the devices are measured to be in the range of 10 mV and 10 μA cm−2. Combining these figures for the best device gives a maximum possible power density of 0.4 mW cm−3. Systematic testing of the devices is performed showing that the voltage output increases linearly with applied stress, and is reduced significantly by illumination with super‐band gap light. This provides strong evidence that the voltage output results from piezoelectric effects in the ZnO. The behavior of the devices is explained by considering the time‐dependent changes in band structure resulting from the straining of a piezoelectric material within a p‐n junction. It is shown that the rate of screening of the depolarisation field determines the power output of a piezoelectric energy harvesting device. This model is consistent with the behavior of a number of previous devices utilising the piezoelectric effect in ZnO.
Mine-site derived particulate matter exposure exacerbates neurological and pulmonary inflammatory outcomes in an autoimmune mouse model

ABSTRACT The Southwestern United States has a legacy of industrial mining due to the presence of rich mineral ore deposits. The relationship between environmental inhaled particulate matter (PM) exposures and neurological outcomes within an autoimmune context is understudied. The aim of this study was to compare two regionally-relevant dusts from high-priority abandoned mine-sites, Claim 28 PM, from Blue Gap Tachee, AZ and St. Anthony mine PM, from the Pueblo of Laguna, NM and to expose autoimmune-prone mice (NZBWF1/J). Mice were randomly assigned to one of three groups (n = 8/group): DM (dispersion media, control), Claim 28 PM, or St. Anthony PM, subjected to oropharyngeal aspiration of (100 µg/50 µl), once per week for a total of 4 consecutive doses. A battery of immunological and neurological endpoints was assessed at 24 weeks of age including: bronchoalveolar lavage cell counts, lung gene expression, brain immunohistochemistry, behavioral tasks and serum autoimmune biomarkers. Bronchoalveolar lavage results demonstrated a significant increase in number of polymorphonuclear neutrophils following Claim 28 and St. Anthony mine PM aspiration. Lung mRNA expression showed significant upregulation in CCL-2 and IL-1ß following St. Anthony mine PM aspiration. In addition, neuroinflammation was present in both Claim 28 and St. Anthony mine-site derived PM exposure groups. Behavioral tasks resulted in significant deficits as determined by Y-maze new arm frequency following Claim 28 aspiration. Neutrophil elastase was significantly upregulated in the St. Anthony mine exposure group. Interestingly, there were no significant changes in serum autoantigens suggesting systemic inflammatory effects may be mediated through other molecular mechanisms following low-dose PM exposures.
Body Mass Index and Its Change from Adolescence to Adulthood Are Closely Related to the Risk of Adult Metabolic Syndrome in China

Aims To investigate the influence of body mass index (BMI) and its change from adolescence to adulthood (ΔBMI) on the risk of metabolic syndrome (MetS) in early adulthood. Methods We selected 931 students from 12 to 16 years of age in Liaoyang City, China. Ninety-three participants from 18 to 22 years of age with complete baseline data were available for follow-up after 5 years. Statistical analysis determined the relationship of MetS at follow-up with baseline BMI (BMIb), ΔBMI, and follow-up BMI (BMIf). Results ΔBMI was positively correlated with the change of waist circumference (ΔWC), systolic blood pressure (ΔSBP), triglycerides (ΔTG), uric acid, and glycosylated hemoglobin (ΔHbA1c) in follow-up (p < 0.05). For every 1 kg/m2 increase in BMIb, ΔBMI, and BMIf, the risk of MetS at follow-up increased 1.201-fold, 1.406-fold, and 1.579-fold, respectively. Both BMIb and ΔBMI were predictive of MetS at follow-up, with prediction thresholds of 23.47 kg/m2 and 1.95 kg/m2. The participants were divided by the predicted BMIb and ΔBMI threshold values into four study groups. Interestingly, the group with lower BMI but a higher increase in BMI presented the same metabolic derangements and Mets% of the group with higher BMI but lower Δ BMI. Conclusion Both BMI of adolescence and ΔBMI were predictive of MetS and cardiovascular risk factors in adulthood. Control of both variables in adolescents would be more effective in decreasing the risk of MetS in young adults than control of BMI alone.
Finding potent inhibitors against SARS-CoV-2 main protease through virtual screening, ADMET, and molecular dynamics simulation studies

Abstract Currently, no antiviral drug or vaccine is available to treat COVID-19 caused by SARS-CoV-2. This underscores an urgent need for developing a drug against SARS-CoV-2. The main protease (3CLpro) of SARS-CoV-2 is considered an essential protein for maintaining the viral life cycle and, therefore, a potential target for drug development. In a recent study, 1000 potential ligands were identified for 3CLpro by screening 1.3 billion compounds from the ZINC15 library. In the current study, we have further screened these 1000 compounds using structure-based virtual screening utilizing the Schrödinger suite and identified nine compounds having a docking score of ∼ −11.0 kcal/mol or less. The top 5 hits display good pharmacological profiles revealing better absorption, proper permeability across the membrane, uniform distribution, and non-toxic. The molecular docking study is further complemented by molecular dynamics simulations of the top 5 docked complexes. The binding free energy analyses via the molecular mechanics generalized Born surface area (MM/GBSA) scheme reveals that ZINC000452260308 is the most potent (ΔGbind = −14.31 kcal/mol) inhibitor. The intermolecular van der Waals interactions mainly drive the 3CLpro-ligand association. This new compound may have great potential as a lead molecule to develop a new antiviral drug to fight against COVID-19. Communicated by Ramaswamy H. Sarma
Bilirubin adsorption for the treatment of severe hyperbilirubinemia after cardiac surgery: A retrospective cohort study

Objective: Severe hyperbilirubinemia after cardiac surgery increases in-hospital and 1-year mortality. Our present study aimed to analyze the safety and efficacy of bilirubin adsorption (BA) in patients with post-cardiac-surgery severe hyperbilirubinemia. Methods: We retrospectively included patients who underwent BA due to severe hyperbilirubinemia after cardiac surgery in our center between January 2015 and December 2018. The change of serum bilirubin, alanine aminotransferase, aspartate aminotransferase, and 30-day and 1-year mortality were assessed as endpoints. Univariate and multivariate analyses were employed to identify the risk factors of patient 30-day mortality. Result: A total of 25 patients with 44 BA treatments were included. One BA treatment reduced total bilirubin (TB) concentration from 431.65 ± 136.34 to 324.83 ± 129.44 µmol/L (p < 0.001), with a reduction rate of 24.8%. No clinically relevant thrombosis of the extracorporeal circuit occurred during the BA treatment. The 30-day and 1-year mortality rates were 68% (n = 18) and 84% (n = 21), respectively. Multivariate analysis identified that TB level before BA treatment (odds ratio [OR] 1.010, 95% confidence interval [CI] 1.000–1.019; p = 0.043) was an independent risk factor of 30-day mortality. Conclusions: BA treatment should be considered as an effective and safe method for the reduction of serum bilirubin in patients with post-cardiac-surgery severe hyperbilirubinemia. Patients with higher TB level before BA treatment had a relatively increased risk of 30-day mortality. Further studies are needed to evaluate the timing of BA for severe hyperbilirubinemia after cardiac surgery.
Adsorption on interstellar analog surfaces : from atoms to organic molecules

Les interactions gaz-grains jouent un role important dans la chimie des milieux interstellaires et protoplanetaires. Le parametre-cle qui gouverne les echanges entre la surface des grains et la phase gazeuse est l’energie d’adsorption Ea. Ce travail a pour but de developper une approche jointe experimentale et theorique afin de determiner les energies d’adsorption pour des atomes et molecules d’interet astrophysique sur des substrats-modeles des surfaces des grains de poussiere interstellaires. Experimentalement, la methode employee est la desorption programmee en temperature (TPD). Le travail a contribue en l’etablissement d’une methode de traitement des courbes de desorption, basee sur une distribution d’energie d’adsorption et utilisant un set limite de donnees a plusieurs rampes de chauffage, pour determiner le couple de parametres de l’equation de Polanyi-Wigner que sont l’energie d’adsorption et le prefacteur. D’un point de vue de la chimie theorique, les energies d’adsorption sont determinees en utilisant la theorie de la fonctionnelle de la densite (DFT) implementee dans le module Vienna Ab initio Simulation Package (VASP). Cette methode permet egalement d’acceder aux geometries d’adsorption, ainsi qu’aux differents sites sur la surface. La methode experimentale a ete validee par une comparaison avec un systeme connu : l’adsorption du methanol CH3OH sur le graphite. L’adsorption des gaz rares Ar/Kr/Xe sur les glaces d’eau a ete etudiee comme un cas d’interet pour la planetologie. L’adsorption de l’acetonitrile (CH3CN) et de son isomere l’isoacetonitrile (CH3NC) sur les surfaces de graphite, de quartz et de glaces d’eau a egalement ete etudiee, puisque ces deux molecules sont detectees dans le milieu interstellaire. Les energies d'adsorption trouvees dans le cadre de ce travail seront integrees dans la base des donnees KIDA.