Miracle-dz/UniFAR-FTUs huggingface dataset:
Association of serum uric acid with blood pressure in Japanese men. Cross-sectional study in work-site group.

BACKGROUND It has been reported that elevated levels of serum uric acid are related to hypertension and cardiovascular disease. Recent studies, however, have found little association between hyperuricemia and hypertension. METHODS AND RESULTS The association of serum uric acid with blood pressure was examined in 3,960 Japanese male workers (18-64 years of age; mean age, 42.3±0.2 years). Systolic blood pressure was significantly correlated with serum uric acid. Multiple regression analysis also showed that both systolic and diastolic blood pressures were independently associated with serum uric acid. When subjects were divided into 6 groups according to blood pressure on the basis of the Japanese Society of Hypertension Guidelines for the Management of Hypertension (JSH 2009), serum uric acid was elevated in a linear fashion as blood pressure increased. A similar relationship was found even in 3,608 subjects who were not taking anti-hypertensive or uric acid-lowering agents. In contrast, no relation was found between serum uric acid and blood pressure in 352 subjects taking anti-hypertensive medicine. CONCLUSIONS Blood pressure is closely associated with serum uric acid. Serum uric acid might be associated with the increase in blood pressure, because there is no relation between serum uric acid and blood pressure in the subjects treated with anti-hypertensive medications.
Aberrant resting-state functional connectivity in limbic and salience networks in treatment--naïve clinically depressed adolescents.

BACKGROUND Depression is prevalent and typically has its onset in adolescence. Resting-state fMRI could help create a better understanding of the underlying neurobiological mechanisms during this critical period. In this study, resting-state functional connectivity (RSFC) is examined using seed regions-of-interest (ROIs) associated with three networks: the limbic network, the default mode network (DMN) and the salience network. METHODS Twenty-six treatment-naïve, clinically depressed adolescents of whom 18 had comorbid anxiety, and 26 pair-wise matched healthy controls underwent resting-state fMRI. The three networks were investigated using a seed-based ROI approach with seeds in the bilateral amygdala (limbic network), bilateral dorsal anterior cingulate cortex (dACC; salience network) and bilateral posterior cingulate cortex (default mode network). RESULTS Compared to healthy controls, clinically depressed adolescents showed increased RSFC of the left amygdala with right parietal cortical areas, and decreased right amygdala RSFC with left frontal cortical areas including the ACC, as well as with right occipito-parietal areas. The bilateral dACC showed decreased RSFC with the right middle frontal gyrus, frontal pole, and inferior frontal gyrus in clinically depressed adolescents. No abnormalities in DMN RSFC were found, and differences in RSFC did not correlate with clinical measures. CONCLUSIONS The aberrant RSFC of the amygdala network and the dACC network may be related to altered emotion processing and regulation in depressed adolescents. Our results provide new insights into RSFC in clinically depressed adolescents and future models on adolescent depression may include abnormalities in the connectivity of salience network.
Association between cumulative anticholinergic burden and falls and fractures in patients with overactive bladder: US-based retrospective cohort study

Objective To estimate the association between cumulative anticholinergic burden and falls and fractures in patients with overactive bladder (OAB). Design A retrospective claims-based study (2007–2015) of patients with OAB; outcomes from a subset were contrasted to a non-OAB comparison. Setting United States, commercially and Medicare-insured population. Participants 154 432 adults with OAB and 86 966 adults without OAB, mean age of 56 years, and 67.9% women. Main outcome measures Cumulative anticholinergic burden, a unitless value representing exposure over time, was estimated over the 12 months pre-index (‘at baseline’) and every 6 months post index. Burden was categorised as no burden (0), low burden (1–89), medium burden (90–499) or high burden (500+). Unadjusted rates of falls or fractures were estimated, and the increased risk associated with anticholinergic burden (measured at the closest 6-month interval prior to a fall or fracture) was assessed using a Cox proportional hazards model and a marginal structural model. Results Median (IQR) baseline anticholinergic burden was 30 (0.0–314.0) and higher among older (≥65 years, 183 [3.0–713.0]) versus younger (<65 years, 13 [0.0–200.0]) adults. The unadjusted rate of falls or fractures over the period was 5.0 per 100 patient-years, ranging from 3.1 (95% CI 3.0–3.2) for those with no burden, to 7.4 (95% CI 7.1–7.6) for those with high burden at baseline. The adjusted risk of falls and fractures was greater with higher anticholinergic burden in the previous 6 months, with an HR of 1.2 (95% CI 1.2 to 1.3) for low burden versus no burden, to 1.4 (95% CI 1.3 to 1.4) for high versus no burden. Estimates from marginal structural models adjusting for time-varying covariates were lower but remained significantly higher with a higher anticholinergic burden. Rates of falls and fractures were approximately 40% higher among those with OAB (vs those without). Conclusion Higher levels of anticholinergic burden are associated with higher rates of falls and fractures, highlighting the importance of considering anticholinergic burden when treating patients with OAB.
The Treatment of Acute Psychosis Without Neuroleptics: Six-Week Psychopathology Outcome Data From the Soteria Project

Background: Today's treatment of acute psychosis usually includes short-term hospitalization and anti-psychotic drug treatment. The Soteria project compared this form of treatment (control) with that of a small, home-like social environment, usually without neuroleptics (experimental). Method: Newly diagnosed, young, unmarried persons with DSM-11 schizophrenia were randomly assigned to treatment in two experimental and two control settings. Subjects and families were assessed at admission on 29 independent variables. Treatment environments were studied by means of Moos', COPES or WAS scales. Three dependent six week psychopathology outcome measures were collected. Results: The groups were comparable on 25 of 29 admission variables. The environments of the two experimental and two control settings were different from each other. The milieus were similar to each other within each condition. At six weeks, psychopathology in both groups had improved significantly, and similarly, and overall change was the same. Conclusion: Specially designed, replicable milieus were able to reduce acute psychotic symptomatology within six weeks, usually without antipsychotic drugs, as effectively as usual hospital ward treatment that included routine neuroleptic drug use.
Chronic myeloid leukemia‐derived exosomes attenuate adipogenesis of adipose derived mesenchymal stem cells via transporting miR‐92a‐3p

Cancer‐associated cachexia (CAC) has tremendous effects on the patient's tolerance to chemotherapy and the quality of life, especially in the advanced stages, such as the acute and terminal stages of chronic myeloid leukemia (CML). However, the underlying mechanisms and mediators remain unclear. Here, we showed that mice injected with CML‐derived exosomes had significant weight loss and great drop of body fat rate. In the meanwhile, we found that CML‐derived exosomes could be taken up by adipose tissue, and, in turn, suppressed the adipogenic ability of adipose‐derived mesenchymal stem cells (ADSCs). By RNA sequencing, miR‐92a‐3p was found highly expressed in both CML cells and the derivative exosomes. Mechanistically, miR‐92a‐3p inhibited adipogenesis of ADSCs via posttranscriptionally decreasing C/EBPα expression when transferred into the ADSCs with the exosomes, and encapsulating miR‐92a‐3p inhibitor into CML exosomes blocked the antiadipogenic effects of CML exosomes. In addition, we also found that miR‐92a‐3p was highly expressed in exosomes from some other types of cancers that cause cachexia. These results demonstrate that adipogenesis inhibition by tumor‐derived exosomes, mainly exosomal microRNAs like miR‐92a‐3p, are the main mediators for CAC.
Phage therapy: Current status and perspectives

The spread of antimicrobial resistant bacterial pathogens combined with the lack of new drug classes in the antibiotic pipeline causes a resurgence of the use of bacterial viruses (phages) to treat bacterial infections (phage therapy [PT]). There has been a substantial increase in patients subjected to this experimental therapy and emergence of new PT centers in Europe and the United States paralleled by one clinical trial completed in accord with good medical practice (GMP) requirements and a few others underway. What is more, evidence has been accumulating to suggest that phages can also exert anti‐inflammatory and immunomodulatory action which opens new pathways for the development of novel targets for PT. Here we present the status quo of the PT, recent regulatory, and clinical developments as well as new perspectives for its wider application in clinical medicine.
Ultrasound Velocity Through the Cortex of Phalanges, Radius, and Tibia in Normal and Osteoporotic Postmenopausal Women Using a New Multisite Quantitative Ultrasound Device

Damilakis J, Papadokostakis G, Vrahoriti H, et al. Ultrasound velocity through the cortex of phalanges, radius, and tibia in normal and osteoporotic postmenopausal women using a new multisite quantitative ultrasound device. Invest Radiol 2003;38:207–211. Rationale and Objectives.To assess a new multisite quantitative ultrasound (QUS) device (Sunlight Omnisense 7000 S) suitable for the measurement of speed of sound (SOS) in the phalanges, radius, and tibia. Methods.The study group consisted of 270 healthy Caucasian postmenopausal patients (mean age: 60.0 ± 7.6 years) and 53 Caucasian postmenopausal patients (mean age: 67.2 ± 7.4 years) with osteoporotic fractures. Measurements of SOS and bone mineral density (BMD) were carried out in all subjects. Results.Intraobserver in vivo short-term precision was on average 0.76% for the radius, 0.47% for the tibia, and 1.54% for the phalanges. The interobserver precision ranged from 0.77% to 2.39%. Measurements of SOS at the 3 skeletal sites were significantly correlated (r = 0.28–0.44;P < 0.001). Significant correlations were found between SOS at all sites and BMD (r = 0.21–0.41;P < 0.001). The odds ratio for fracture prediction for SOS was 1.47 for tibia, 1.69 for radius, and 2.69 for phalanx. The corresponding odds ratios for BMD at the lumbar spine, femoral neck, and total hip ranged from 2.08 to 3.26. The area under the receiver operating characteristic curve ranged from 0.611 to 0.741 for SOS measurements and from 0.745 to 0.797 for BMD measurements. Conclusions.The Omnisense multisite QUS device exhibits reproducible performance. Among the QUS variables, the phalangeal SOS provides the best discrimination of fracture patients.
Outbreak of Listeria monocytogenes in South Africa, 2017–2018: Laboratory Activities and Experiences Associated with Whole-Genome Sequencing Analysis of Isolates

Abstract In South Africa, a progressive increase in listeriosis cases was noted from mid-June 2017, heralding what was to become the world's largest listeriosis outbreak. A total of 1060 cases were reported for the period January 1, 2017 to July 17, 2018. We describe laboratory activities, experiences, and results of whole-genome sequencing (WGS) analysis of Listeria monocytogenes isolates associated with this outbreak. Bacteria were identified using the VITEK-2 COMPACT 15 microbial identification system. WGS was performed using Illumina MiSeq technology. WGS data were analyzed using CLC Genomics Workbench Software and free-to-use on-line analysis tools/pipelines. Multilocus sequence typing (MLST) showed that 91% of clinical isolates were sequence type 6 (ST6), determining that the outbreak was largely associated with L. monocytogenes ST6. Epidemiological and laboratory findings led to investigation of a large ready-to-eat processed meat production facility in South Africa, named Enterprise Foods. L. monocytogenes ST6 was found in environmental sampling swabs of the production facility and in ready-to-eat processed meat products (including polony, a product similar to bologna sausage) manufactured at the facility. ST6 isolates, sourced at the Enterprise Foods production facility and from Enterprise food products, were shown by single nucleotide polymorphism (SNP) analysis to be highly related to clinical isolates; these nonclinical ST6 isolates showed <10 SNP differences when compared to clinical ST6 isolates. Core-genome MLST showed that clinical ST6 isolates and Enterprise-related ST6 isolates had no more than 4 allele differences between each other, suggestive of a high probability of epidemiological relatedness. WGS data interpreted together with epidemiological data concluded that the source of the listeriosis outbreak was ready-to-eat processed meat products manufactured by Enterprise Foods. Listeriosis has now been added to the South African list of mandatory notifiable medical conditions. Surveillance systems have been strengthened to facilitate prevention and early detection of listeriosis outbreaks.
Clinical Pharmacokinetics, Pharmacodynamics, Safety and Efficacy of Liposomal Amphotericin B

Abstract Since its introduction in the 1990s, liposomal amphotericin B (LAmB) continues to be an important agent for the treatment of invasive fungal diseases caused by a wide variety of yeasts and molds. This liposomal formulation was developed to improve the tolerability of intravenous amphotericin B, while optimizing its clinical efficacy. Since then, numerous clinical studies have been conducted, collecting a comprehensive body of evidence on its efficacy, safety, and tolerability in the preclinical and clinical setting. Nevertheless, insights into the pharmacokinetics and pharmacodynamics of LAmB continue to evolve and can be utilized to develop strategies that optimize efficacy while maintaining the compound’s safety. In this article, we review the clinical pharmacokinetics, pharmacodynamics, safety, and efficacy of LAmB in a wide variety of patient populations and in different indications, and provide an assessment of areas with a need for further clinical research.
Gray and white matter alterations in cocaine addiction: Clinical and methodological aspects

Departamento e Instituto de Psiquiatria, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil 2 Instituto de Psiquiatria, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil 3 Laboratory of Psychiatric Neuroimaging (LIM‐21), Instituto de Psiquiatria, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil
Whole limb kinematics are preferentially conserved over individual joint kinematics after peripheral nerve injury

SUMMARY Biomechanics and neurophysiology studies suggest whole limb function to be an important locomotor control parameter. Inverted pendulum and mass-spring models greatly reduce the complexity of the legs and predict the dynamics of locomotion, but do not address how numerous limb elements are coordinated to achieve such simple behavior. As a first step, we hypothesized whole limb kinematics were of primary importance and would be preferentially conserved over individual joint kinematics after neuromuscular injury. We used a well-established peripheral nerve injury model of cat ankle extensor muscles to generate two experimental injury groups with a predictable time course of temporary paralysis followed by complete muscle self-reinnervation. Mean trajectories of individual joint kinematics were altered as a result of deficits after injury. By contrast, mean trajectories of limb orientation and limb length remained largely invariant across all animals, even with paralyzed ankle extensor muscles, suggesting changes in mean joint angles were coordinated as part of a long-term compensation strategy to minimize change in whole limb kinematics. Furthermore, at each measurement stage (pre-injury, paralytic and self-reinnervated) step-by-step variance of individual joint kinematics was always significantly greater than that of limb orientation. Our results suggest joint angle combinations are coordinated and selected to stabilize whole limb kinematics against short-term natural step-by-step deviations as well as long-term, pathological deviations created by injury. This may represent a fundamental compensation principle allowing animals to adapt to changing conditions with minimal effect on overall locomotor function.
The Immune Microenvironment in Hormone Receptor–Positive Breast Cancer Before and After Preoperative Chemotherapy

Purpose: Hormone receptor–positive/HER2-negative (HR+/HER2−) breast cancer is associated with low levels of stromal tumor-infiltrating lymphocytes (sTIL) and PD-L1, and demonstrates poor responses to checkpoint inhibitor therapy. Evaluating the effect of standard chemotherapy on the immune microenvironment may suggest new opportunities for immunotherapy-based approaches to treating HR+/HER2− breast tumors. Experimental Design: HR+/HER2− breast tumors were analyzed before and after neoadjuvant chemotherapy. sTIL were assessed histologically; CD8+ cells, CD68+ cells, and PD-L1 staining were assessed immunohistochemically; whole transcriptome sequencing and panel RNA expression analysis (NanoString) were performed. Results: Ninety-six patients were analyzed from two cohorts (n = 55, Dana-Farber cohort; n = 41, MD Anderson cohort). sTIL, CD8, and PD-L1 on tumor cells were higher in tumors with basal PAM50 intrinsic subtype. Higher levels of tissue-based lymphocyte (sTIL, CD8, PD-L1) and macrophage (CD68) markers, as well as gene expression markers of lymphocyte or macrophage phenotypes (NanoString or CIBERSORT), correlated with favorable response to neoadjuvant chemotherapy, but not with improved distant metastasis-free survival in these cohorts or a large gene expression dataset (N = 302). In paired pre-/postchemotherapy samples, sTIL and CD8+ cells were significantly decreased after treatment, whereas expression analyses (NanoString) demonstrated significant increase of multiple myeloid signatures. Single gene expression implicated increased expression of immunosuppressive (M2-like) macrophage-specific genes after chemotherapy. Conclusions: The immune microenvironment of HR+/HER2− tumors differs according to tumor biology. This cohort of paired pre-/postchemotherapy samples suggests a critical role for immunosuppressive macrophage expansion in residual disease. The role of macrophages in chemoresistance should be explored, and further evaluation of macrophage-targeting therapy is warranted.
Theiler's virus infection of 129Sv mice that lack the interferon alpha/beta or interferon gamma receptors

The Daniels strain of Theiler's virus causes a persistent infection of the white matter of spinal cord of susceptible mice, with chronic inflammation and primary demyelination. Inbred 129Sv mice are resistant to this infection; they present with mild encephalomyelitis and clear the infection within a matter of days. A very different outcome was observed with inbred 129Sv mice whose receptors for interferon alpha/beta or interferon gamma had been inactivated by homologous recombination. The former presented severe encephalomyelitis with acute infection of neurons, particularly in brain and hippocampus, and extensive infection with necrosis of the choroid plexus. Most animals died of this acute disease. The latter, presented the same early encephalomyelitis as the control 129Sv mice. However, they remained persistently infected and developed a very severe late infection of the white matter with extensive primary demyelination. This late disease looked like an exacerbated form of the chronic demyelinating disease observed in susceptible inbred mice such as the SJL/J or FVB strains. Our results show that the two interferon systems play nonredundant roles in the resistance of the 129Sv mouse to the infection by Theiler's virus. They also lend support to the notion that the Ifg gene is involved in the resistance/susceptibility of inbred strains of mice to persistent infection by this picornavirus.
Statistical Phylogenetic Tree Analysis Using Differences of Means

We propose a statistical method to test whether two phylogenetic trees with given alignments are significantly incongruent. Our method compares the two distributions of phylogenetic trees given by two input alignments, instead of comparing point estimations of trees. This statistical approach can be applied to gene tree analysis for example, detecting unusual events in genome evolution such as horizontal gene transfer and reshuffling. Our method uses difference of means to compare two distributions of trees, after mapping trees into a vector space. Bootstrapping alignment columns can then be applied to obtain p-values. To compute distances between means, we employ a “kernel method” which speeds up distance calculations when trees are mapped in a high-dimensional feature space, e.g., splits or quartets feature space. In this pilot study, first we test our statistical method on data sets simulated under a coalescence model, to test whether two alignments are generated by congruent gene trees. We follow our simulation results with applications to data sets of gophers and lice, grasses and their endophytes, and different fungal genes from the same genome. A companion toolkit, Phylotree, is provided to facilitate computational experiments.
Comparative chemical analysis of indian bidi and American cigarette smoke

Human data suggest an association between bidi smoking and cancer of the oral cavity, pharynx, larynx, esophagus and lung. The mainstream smoke of a popular Indian bidi and a popular US non‐filter cigarette were analyzed. Compared to cigarette smoke, bidi smoke has a high content of several toxic agents such as carbon monoxide (7.7 vs 3.5 vol. %), ammonia (284 vs 180 μg), hydrogen cyanide (903 vs 445 μg), phenol (250 vs 150 μg), other volatile phenols (264 vs 173 μg) and carcinogenic hydrocarbons, benz[a]anthracene (117 vs 81 μg) and benzo[a]pyrene (78 vs 47 ng). These chemical data suggest that the smoke of bidis has a carcinogenic activity and underline the need for bioassaying this inhalant.
Anticipatory alpha oscillation predicts attentional selection and hemodynamic response

In covert visual attention, one fundamental question is how advance knowledge facilitates subsequent neural processing and behavioral performance. In this study, with a rapid event‐related simultaneous electroencephalography (EEG) and functional near infrared spectroscopy recording in humans, we explored the potential contribution of anticipatory electrophysiological activation and hemodynamic activation by examining how anticipatory low‐frequency oscillations and changes in oxygenated hemoglobin (HbO) concentration influence the subsequent event‐related potential (ERP) marker of attentional selection. We found that expecting a target led to both a posterior lateralization of alpha‐band (8–12 Hz) oscillation power and a lateralization of HbO response over the visual cortex. Importantly, the magnitude of cue‐induced alpha lateralization was positively correlated with the nearby HbO lateralization in the visual cortex, and such a cue‐induced alpha lateralization predicted the subsequent target‐evoked N2pc amplitudes assumed to reflect attentional selection. Our results suggest that each individual's attentional selection biomarker as reflected by N2pc is predictable in advance via the anticipation‐induced alpha lateralization, and such cue‐induced alpha lateralization seems to play an important role in the functional coupling effects between the low‐frequency EEG and the nearby hemodynamic activation.