Miracle-dz/UniFAR-FTUs huggingface dataset:
Cardiotoxicity of aromatase inhibitors and tamoxifen in postmenopausal women with breast cancer: a systematic review and meta-analysis of randomized controlled trials

Background Aromatase inhibitors (AIs) have been associated with cardiovascular disease in adjuvant randomized controlled trials (RCTs) comparing these drugs to tamoxifen. However, it is unclear whether this risk is real or due to cardioprotective effects of tamoxifen. To address this question, we conducted a systematic review and meta-analysis of all RCTs of AIs and tamoxifen in adjuvant and extended adjuvant setting. Patients and methods We searched PubMed, Embase (OVID), Cochrane CENTRAL, WHO International Clinical Trials Registry Platform, and ClinicalTrials.gov from inception to June 2016 for all RCTs comparing cardiovascular and cerebrovascular safety of AIs to tamoxifen, AIs to placebo or no-treatment, or tamoxifen to placebo or no-treatment in the adjuvant or extended adjuvant setting. Relative risks (RRs) were pooled using DerSimonian and Laird random-effects models with analyses stratified by RCT design. Results A total of 19 RCTs were included in the meta-analysis (n = 62 345). In the adjuvant setting, AIs were associated with a 19% (RR: 1.19, 95% confidence interval [CI]: 1.07-1.34) increased risk of cardiovascular events compared with tamoxifen. AIs were not associated with an increased risk compared with placebo in the extended-adjuvant setting (RR: 1.01, 95% CI: 0.85-1.20). In the adjuvant setting, tamoxifen was associated with a 33% (RR: 0.67, 95% CI: 0.45-0.98) decreased risk compared with placebo or no-treatment. The results from extended adjuvant RCTs comparing tamoxifen to placebo were inconclusive but suggestive of a small protective effect (RR: 0.91, 95% CI: 0.77-1.07). Conclusions The increased risk of cardiovascular events with AIs relative to tamoxifen is likely the result of cardioprotective effects of the latter. This new evidence should be considered when assessing the benefits and risks of AIs in the treatment of breast cancer.
Reduced Productivity of Culex pipiens and Cx. restuans (Diptera: Culicidae) Mosquitoes in Parking Area Catch Basins in the Northeast Chicago Metropolitan Area

ABSTRACT: From June to September, 2016, 100 catch basins in eight parking areas were monitored weekly for the presence of mosquito pupae in the operational area of the North Shore Mosquito Abatement District (NSMAD) located just north of Chicago, IL, U.S.A. Weekly results from these basins were compared to weekly samples taken from residential street catch basins, the most common type of catch basin treated seasonally by the NSMAD with larvicides. Over the 17 study weeks, residential street basins had a mean rate of productivity (pupae per basin-visit) 12 times that of parking area catch basins. The two parking area sites with the highest mean rate of productivity were associated with county forest preserves. Productivity in both street and parking area basins was positively associated with the presence of three or more deciduous trees within 20 m of basins and if they were located directly adjacent to curbs. Alternatively, productivity was negatively associated with the proportion of impervious surface within 10 m of basins and weekly rainfall. Findings suggest that reduced catch basin larvicide applications may be appropriate in many parking area sites.
A CMOS K-Band 6-bit Attenuator With Low Phase Imbalance for Phased Array Applications

A 6-bit digital-controlled attenuator with low phase imbalance for a K-band phased array system is presented in this paper. To decrease the insertion phase difference, the proposed design adopts a phase correction capacitor in the shunt branch of the conventional switched T/Pi structure. The capacitor and the parallel resistor compose a phase compensation network to correct the insertion phase error. The attenuator is designed and fabricated in <inline-formula> <tex-math notation="LaTeX">$0.18~\mu \text{m}$ </tex-math></inline-formula> CMOS process. From 19 to 21 GHz, the insertion loss is 7.2–8 dB. The rms phase imbalance is less than 3.8° over 19–21 GHz. The attenuator has a maximum attenuation range of 32 dB with 0.5-dB step (64 states). The core cell chip size is 1.32 mm <inline-formula> <tex-math notation="LaTeX">$\times0.34$ </tex-math></inline-formula> mm excluding pads.
Genomic sequences of HLA‐A*68:169, HLA‐B*07:298 and HLA‐B*39:129.

Three new HLA class I alleles were described in the Spanish population. HLA‐A*68:169 and ‐B*39:129 show one amino acid replacement at the α1‐domain, compared to A*68:02 (P47 > L47) and ‐B*39:06 (S11 > A11), respectively. HLA‐B*07:298 presents one nucleotide mutation within exon 1, resulting in a new amino acid position −14, L>Q, which has not been previously described in any HLA protein. Prediction of the B*07:298 signal peptide cleavage did not show significant differences in comparison with that obtained for the rest of HLA‐B genes.
Mutation supply and the repeatability of selection for antibiotic resistance

Whether evolution can be predicted is a key question in evolutionary biology. Here we set out to better understand the repeatability of evolution, which is a necessary condition for predictability. We explored experimentally the effect of mutation supply and the strength of selective pressure on the repeatability of selection from standing genetic variation. Different sizes of mutant libraries of antibiotic resistance gene TEM-1 β-lactamase in Escherichia coli, generated by error-prone PCR, were subjected to different antibiotic concentrations. We determined whether populations went extinct or survived, and sequenced the TEM gene of the surviving populations. The distribution of mutations per allele in our mutant libraries followed a Poisson distribution. Extinction patterns could be explained by a simple stochastic model that assumed the sampling of beneficial mutations was key for survival. In most surviving populations, alleles containing at least one known large-effect beneficial mutation were present. These genotype data also support a model which only invokes sampling effects to describe the occurrence of alleles containing large-effect driver mutations. Hence, evolution is largely predictable given cursory knowledge of mutational fitness effects, the mutation rate and population size. There were no clear trends in the repeatability of selected mutants when we considered all mutations present. However, when only known large-effect mutations were considered, the outcome of selection is less repeatable for large libraries, in contrast to expectations. We show experimentally that alleles carrying multiple mutations selected from large libraries confer higher resistance levels relative to alleles with only a known large-effect mutation, suggesting that the scarcity of high-resistance alleles carrying multiple mutations may contribute to the decrease in repeatability at large library sizes.
Is foetal hyperexposure to androgens a cause of PCOS?

BACKGROUND Polycystic ovary syndrome (PCOS) is the most common endocrinopathy affecting reproductive-aged women. The pathophysiology of this syndrome is still not completely understood but recent evidence suggests that the intra-uterine environment may be a key factor in the pathogenesis of PCOS, in particular, hyperexposure of the foetus to androgens. High concentrations of maternal serum testosterone during pregnancy have been shown to influence behaviour during childhood, the prevalence of autism disorders and anti-Mullerian hormone (AMH) concentrations in adolescence. They are also thought to re-programme the female reproductive axis to induce the features of PCOS in later life: oligo/anovulation, polycystic ovaries, hyperandrogenism and insulin resistance (IR). Support for this developmental theory for the aetiology of PCOS is gathering momentum, following results from first animal studies and now human data, which lend credence to many aspects of this hypothesis. OBJECTIVE AND RATIONALE In this review the recent available evidence is presented to support the hypothesis that hyperandrogenic changes in the intra-uterine environment could play a major part in the aetiological basis of PCOS. SEARCH METHODS An extensive PubMED and MEDline database search was conducted. Relevant studies were identified using a combination of search terms: 'polycystic ovary syndrome', 'PCOS', 'aetiology', 'anti-Mullerian hormone', 'AMH', 'pathogenesis', 'kisspeptin', 'hyperandrogenism', 'insulin resistance', 'metabolic factors', 'placenta', 'developmental hypothesis', 'genetic and epigenetic origins'. OUTCOMES A total of 82 studies were finally included in this review. There is robust evidence that a hyperandrogenic intra-uterine environment 'programmes' the genes concerned with ovarian steroidogenesis, insulin metabolism, gonadotrophin secretion and ovarian follicle development resulting in the development of PCOS in adult life. WIDER IMPLICATIONS Once the evidence supporting this hypothesis has been expanded by additional studies, the door would be open to find innovative treatments and preventative measures for this very prevalent condition. Such measures could considerably ease the human and economic burden that PCOS creates.
Exposure-Response Relationships during Free-Access Intravenous Alcohol Self-Administration in Nondependent Drinkers: Influence of Alcohol Expectancies and Impulsivity

Abstract Background: Self-administration is a hallmark of all addictive drugs, including alcohol. Human laboratory models of alcohol self-administration have characterized alcohol-seeking behavior and served as surrogate measures of the effectiveness of pharmacotherapies for alcohol use disorders. Intravenous alcohol self-administration is a novel method that assesses alcohol exposure driven primarily by the pharmacological response to alcohol and may have utility in characterizing unique behavioral and personality correlates of alcohol-seeking and consumption. Methods: This study examined exposure-response relationships for i.v. alcohol self-administration, and the influence of impulsivity and alcohol expectancy, in healthy, nondependent drinkers (n=112). Participants underwent a 2.5-hour free-access i.v. alcohol self-administration session using the Computerized Alcohol Infusion System. Serial subjective response measures included the Drug Effects Questionnaire and Alcohol Urge Questionnaire. To characterize the motivational aspects of alcohol consumption prior to potential acute adaptation, the number of self-infusions in the first 30 minutes of the free-access session was used to classify participants as low- and high-responders. Results: High-responders showed greater subjective responses during i.v. alcohol self-administration compared with low responders, reflecting robust exposure-driven hedonic responses to alcohol. High-responders also reported heavier drinking patterns and lower scores for negative alcohol expectancies on the Alcohol Effects Questionnaire. High-responders also showed higher measures of impulsivity on a delayed discounting task, supporting previous work associating impulsivity with greater alcohol use and problems. Conclusions: These findings indicate that early-phase measures of free-access i.v. alcohol self-administration are particularly sensitive to the rewarding and motivational properties of alcohol and may provide a unique phenotypic marker of alcohol-seeking behavior.
Review PROBIOTIC YOGHURT MANUFACTURED WITH TIGER-NUT EXTRACT (CYPERUS ESCULENTUS ) AS A FUNCTIONAL DAIRY FOOD

Tiger-nut ( cyperus esculentus ) has nutritional and health benefits. A probiotic yoghurt fortified with tiger-nut extract (TNE) was manufactured using the conventional yoghurt starter together with Bifidobacterium bifidum as a probiotic bacterial strain . Tiger-nut extract was prepared and added at a concentration of 10, 20, and 30% to Buffalo's skim milk. The chemical, rheological and sensory properties of the final product, as well as, the viability of the LAB were evaluated during 10 days of storage at refrigeration temperature. The (LAB) strains have showed relatively higher counts in yoghurt fortified with TNE than the corresponding control. No changes in post acidification of yoghurt treatments were observed. Yoghurt containing 10% TNE have showed the highest apparent viscosity and the lowest whey syneresis , however the product containing 30% have showed the lowest apparent viscosity and highest whey syneresis . No significant differences were observed in sensory properties among yoghurt containing 10 or 20% TNE and control. The results indicated that, addition of 10 or 20% TNE could serve as a good fortification for manufacturing of nutritional and therapeutic yoghurt since it will not influence the chemical and sensory properties, instead it will improve the rheological properties of the final product.
Reduced Specificity of Hippocampal and Posterior Ventrolateral Prefrontal Activity during Relational Retrieval in Normal Aging

Neuroimaging studies of episodic memory in young adults demonstrate greater functional neural activity in ventrolateral pFC and hippocampus during retrieval of relational information as compared with item information. We tested the hypothesis that healthy older adults—individuals who exhibit behavioral declines in relational memory—would show reduced specificity of ventrolateral prefrontal and hippocampal regions during relational retrieval. At study, participants viewed two nouns and were instructed to covertly generate a sentence that related the words. At retrieval, fMRIs were acquired during item and relational memory tasks. In the relational task, participants indicated whether the two words were previously seen together. In the item task, participants indicated whether both items of a pair were previously seen. In young adults, left posterior ventrolateral pFC and bilateral hippocampal activity was modulated by the extent to which the retrieval task elicited relational processing. In older adults, activity in these regions was equivalent for item and relational memory conditions, suggesting a reduction in ventrolateral pFC and hippocampal specificity with normal aging.
Clinical Named Entity Recognition Using Deep Learning Models

Clinical Named Entity Recognition (NER) is a critical natural language processing (NLP) task to extract important concepts (named entities) from clinical narratives. Researchers have extensively investigated machine learning models for clinical NER. Recently, there have been increasing efforts to apply deep learning models to improve the performance of current clinical NER systems. This study examined two popular deep learning architectures, the Convolutional Neural Network (CNN) and the Recurrent Neural Network (RNN), to extract concepts from clinical texts. We compared the two deep neural network architectures with three baseline Conditional Random Fields (CRFs) models and two state-of-the-art clinical NER systems using the i2b2 2010 clinical concept extraction corpus. The evaluation results showed that the RNN model trained with the word embeddings achieved a new state-of-the- art performance (a strict F1 score of 85.94%) for the defined clinical NER task, outperforming the best-reported system that used both manually defined and unsupervised learning features. This study demonstrates the advantage of using deep neural network architectures for clinical concept extraction, including distributed feature representation, automatic feature learning, and long-term dependencies capture. This is one of the first studies to compare the two widely used deep learning models and demonstrate the superior performance of the RNN model for clinical NER.
Resting-state brain function in schizophrenia and psychotic bipolar probands and their first-degree relatives

Background Schizophrenia (SCZ) and psychotic bipolar disorder (PBD) share considerable overlap in clinical features, genetic risk factors and co-occurrence among relatives. The common and unique functional cerebral deficits in these disorders, and in unaffected relatives, remain to be identified. Method A total of 59 healthy controls, 37 SCZ and 57 PBD probands and their unaffected first-degree relatives (38 and 28, respectively) were studied using resting-state functional magnetic resonance imaging (rfMRI). Regional cerebral function was evaluated by measuring the amplitude of low-frequency fluctuations (ALFF). Areas with ALFF alterations were used as seeds in whole-brain functional connectivity analysis. We then tested whether abnormalities identified in probands were present in unaffected relatives. Results SCZ and PBD probands both demonstrated regional hypoactivity in the orbital frontal cortex and cingulate gyrus, as well as abnormal connectivity within striatal-thalamo-cortical networks. SCZ probands showed greater and more widely distributed ALFF alterations including the thalamus and bilateral parahippocampal gyri. Increased parahippocampal ALFF was related to positive symptoms and cognitive deficit. PBD patients showed uniquely increased functional connectivity between the thalamus and bilateral insula. Only PBD relatives showed abnormal connectivity within striatal-thalamo-cortical networks seen in both proband groups. Conclusions The present findings reveal a common pattern of deficits in frontostriatal circuitry across SCZ and PBD, and unique regional and functional connectivity abnormalities that distinguish them. The abnormal network connectivity in PBD relatives that was present in both proband groups may reflect genetic susceptibility associated with risk for psychosis, but within-family associations of this measure were not high.
Frictional energy dissipation in Hertzian contact under biaxial tangential harmonically varying loads

If a Hertzian contact is loaded by a tangential force which varies direction in time, the classical solution due to Cattaneo and Mindlin does not hold, and a numerical solution is needed. Here, we deal with the important practical case when the force describes an ellipse in the loading space, that is, the components have harmonic variation, with the in-phase (uniaxial) case being the limiting Cattaneo–Mindlin problem. We observe convergence to a steady state within the second cycle of oscillatory loading, and we describe the dependence of frictional dissipation, important both as a source of structural damping and as an indicator of potential fretting damage, on the parameters of the problem. The results show that the dissipation depends significantly on the biaxiality ratio between the tangential load components, particularly so when their amplitude is close to the full sliding limit. We find steady-state dissipation to be higher than the corresponding Cattaneo–Mindlin case for low tangential forces (with a maximum of dissipation for a rotating load). The increase is of the order of 15% only, whereas the decrease for large tangential forces seems to be more significant. This is vaguely similar to the case recently studied when the tangential force was of constant direction, but normal and tangential loads were oscillating harmonically and out of phase: this suggests that in the general case, the dissipation may be significantly larger when all the loads are out of phase.
The International Dimension of the U.S. HIV Transmission Network and Onward Transmission of HIV Recently Imported into the United States.

The majority of HIV infections in the United States can be traced back to a single introduction in late 1960s or early 1970s. However, it remains unclear whether subsequent introductions of HIV into the United States have given rise to onward transmission. Genetic transmission networks can aid in understanding HIV transmission. We constructed a genetic distance-based transmission network using HIV-1 pol sequences reported to the U.S. National HIV Surveillance System (n = 41,539) and all publicly available non-U.S. HIV-1 pol sequences (n = 86,215). Of the 13,145 U.S. persons clustered in the network, 457 (3.5%) were genetically linked to a potential transmission partner outside the United States. For internationally connected persons residing in but born outside the United States, 61% had a connection to their country of birth or to another country that shared a language with their country of birth. Bayesian molecular clock phylogenetic analyses indicate that introduced nonsubtype B infections have resulted in onward transmission within the United States.
Stir bar-sorptive extraction, solid phase extraction and liquid-liquid extraction for levetiracetam determination in human plasma: comparing recovery rates

Levetiracetam (LEV), an antiepileptic drug (AED) with favorable pharmacokinetic profile, is increasingly being used in clinical practice, although information on its metabolism and disposition are still being generated. Therefore a simple, robust and fast liquid-liquid extraction (LLE) followed by high-performance liquid chromatography method is described that could be used for both pharmacokinetic and therapeutic drug monitoring (TDM) purposes. Moreover, recovery rates of LEV in plasma were compared among LLE, stir bar-sorptive extraction (SBSE), and solid-phase extraction (SPE). Solvent extraction with dichloromethane yielded a plasma residue free from usual interferences such as commonly co-prescribed AEDs, and recoveries around 90% (LLE), 60% (SPE) and 10% (SBSE). Separation was obtained using reverse phase Select B column with ultraviolet detection (235 nm). Mobile phase consisted of methanol:sodium acetate buffer 0.125 M pH 4.4 (20:80, v/v). The method was linear over a range of 2.8-220.0 µg mL-1. The intra- and inter-assay precision and accuracy were studied at three concentrations; relative standard deviation was less than 10%. The limit of quantification was 2.8 µg mL-1. This robust method was successfully applied to analyze plasma samples from patients with epilepsy and therefore might be used for pharmacokinetic and TDM purposes.
Clinical and Radiological Outcomes Comparing Percutaneous Chevron-Akin Osteotomies vs Open Scarf-Akin Osteotomies for Hallux Valgus

Background: Minimally invasive surgeries have gained popularity due to less soft tissue trauma and better wound healing. To date, limited studies have compared the outcomes of percutaneous and open osteotomies. This study aims to investigate the clinical and radiological outcomes of percutaneous chevron-Akin osteotomies vs open scarf–Akin osteotomies at 24-month follow-up. Method: We reviewed a prospectively collected database in a tertiary hospital hallux valgus registry. Twenty-nine feet that underwent a percutaneous technique were matched to 58 feet that underwent open scarf and Akin osteotomies. Clinical outcome measures assessed included visual analog scale (VAS) scores, American Orthopaedic Foot & Ankle Society Hallux Metatarsophalangeal-Interphalangeal score (AOFAS Hallux MTP-IP), and Short Form 36 (SF-36) Health Survey. Radiological outcomes included hallux valgus angle (HVA) and intermetatarsal angle (IMA). All patients were prospectively followed up at 6 and 24 months. Results: Both groups showed comparable clinical and radiological outcomes at the 24-month follow-up. However, the percutaneous group demonstrated less pain in the perioperative period (P < .001). There were significant differences in the change in HVA between the groups but comparable radiological outcomes in IMA at the 24-month follow-up. The percutaneous group demonstrated shorter length of operation (P < .001). There were no complications in the percutaneous group but 3 wound complications in the open group. Conclusions: We conclude that clinical and radiological outcomes of third-generation percutaneous chevron-Akin osteotomies were comparable with open scarf and Akin osteotomies at 24 months but with significantly less perioperative pain, shorter length of operation, and less risk of wound complications. Level of Evidence: Level III, retrospective comparative series.