Miracle-dz/UniFAR-FTUs huggingface dataset:
In Vitro Hepatic Oxidative Biotransformation of Trimethoprim

Trimethoprim (TMP) has been widely used since the 1960s, both alone and in combination with sulfamethoxazole. Unfortunately, information regarding the role that cytochrome P450 enzymes (P450s) play in the formation of TMP primary metabolites is scarce. Hence, we undertook in vitro studies to identify and more fully characterize the P450s that catalyze formation of six TMP primary metabolites: TMP 1-N-oxide (1-NO-TMP) and 3-N-oxide (3-NO-TMP), 3′- and 4′-desmethyl-TMP, a benzylic alcohol (Cα-OH-TMP), and an N-acetyl cysteine (NAC) adduct of TMP (Cα-NAC-TMP). Formation kinetics for each TMP metabolite in human liver microsomes (HLMs) were consistent with single-enzyme Michaelis-Menten kinetics, and Km values were markedly above (≥10-fold) the therapeutic concentrations of TMP (50 µM). The combined results from correlation studies between rates of metabolite formation and marker P450 activities in a panel of HLMs along with inhibition studies utilizing selective P450 inhibitors incubated with pooled HLMs suggested that 1-NO-TMP, Cα-NAC-TMP, and Cα-OH-TMP were predominantly formed by CYP3A4. In contrast, 3-NO-TMP was formed predominantly by CYP1A2 in HLMs and inhibited by α-naphthoflavone. 4′-Desmethyl-TMP, which is believed to be a reactive TMP metabolite precursor, was formed by several P450s, including CYP3A4, correlated with multiple P450 activities, but was inhibited primarily by ketoconazole (up to 50%), suggesting that CYP3A4 makes a major contribution to TMP 4′-demethylation. TMP 3′-demethylation was catalyzed by multiple P450s, including CYP2C9, correlated with CYP2C9 activity, and was inhibited by sulfaphenazole (up to 40%). Overall, CYP2C9 and CYP3A4 appear to be the most significant contributors to TMP primary metabolism.
Compartmentalization of antagonistic Ca2+ signals in developing cochlear hair cells

Significance Cochlear inner hair cells (IHCs) are responsible for transducing sound waves and relaying acoustic information to the brain through its afferent synapse. During development, IHCs exhibit sensory-independent activity, supported by voltage-gated Ca2+ influx, which is critical for the normal maturation of the auditory system. This spontaneous activity is modulated by an inhibitory cholinergic input, mediated by nicotinic receptors with unusually high Ca2+ permeability, leading to the activation of hyperpolarizing SK channels. Thus, Ca2+ should play distinct excitatory and inhibitory roles in small, compact IHCs. This work presents evidence for specialized cellular mechanisms that maintain local compartmentalization of Ca2+ signals and prevent synaptic cross-talk. Thus, the cholinergic input preserves its inhibitory signature to ensure normal development of the auditory system. During a critical developmental period, cochlear inner hair cells (IHCs) exhibit sensory-independent activity, featuring action potentials in which Ca2+ ions play a fundamental role in driving both spiking and glutamate release onto synapses with afferent auditory neurons. This spontaneous activity is controlled by a cholinergic input to the IHC, activating a specialized nicotinic receptor with high Ca2+ permeability, and coupled to the activation of hyperpolarizing SK channels. The mechanisms underlying distinct excitatory and inhibitory Ca2+ roles within a small, compact IHC are unknown. Making use of Ca2+ imaging, afferent auditory bouton recordings, and electron microscopy, the present work shows that unusually high intracellular Ca2+ buffering and “subsynaptic” cisterns provide efficient compartmentalization and tight control of cholinergic Ca2+ signals. Thus, synaptic efferent Ca2+ spillover and cross-talk are prevented, and the cholinergic input preserves its inhibitory signature to ensure normal development of the auditory system.
Relationship between changes in blood pressure and left ventricular mass over 1 year in end-stage renal disease

Objective: The optimal timing of blood pressure (BP) measurement is not firmly established for patients undergoing hemodialysis. We sought to assess which BP measurement change best correlates with changes in left ventricular mass index (LVMI) over 1 year in patients with end-stage renal disease. Methods: Fifty-seven patients were included in a prospective cohort study comparing the cardiovascular impact of conversion to in-center nocturnal hemodialysis versus continuing conventional hemodialysis. BP measurements were recorded at different time points (predialysis, after initiation of dialysis, at the intradialytic nadir, and postdialysis) during dialysis sessions over 12 weeks at baseline and after 1-year follow-up. LVMI was independently measured by a single blinded reader using cardiac magnetic resonance imaging at baseline and 1 year. Results: Overall, the mean LVMI was 69.9 g/m2 (standard deviation 15.9) at baseline and 69.6 g/m2 (standard deviation 16.0) at 1 year. The change in initiation mean arterial pressure (MAP) most strongly correlated with the change in LVMI (Pearson correlation coefficient r = 0.71, P < 0.001). The relationship was similar in both dialysis groups and in multivariable analysis. In pairwise comparisons, initiation MAP was more strongly correlated with the change in LVMI than nadir and postdialysis measurements (all P < 0.05). However, the correlation was not stronger than predialysis SBP (P = 0.33). Conclusion: The change in initiation MAP correlated best with the change in LVMI over 1 year in patients undergoing hemodialysis. Further studies are needed to determine whether it represents a potentially useful treatment target to prevent adverse ventricular remodeling, thereby improving cardiovascular outcome. ClinicalTrials.gov Identifier: NCT00718848
Annual estimates of the burden of seasonal influenza in the United States: A tool for strengthening influenza surveillance and preparedness

Estimates of influenza disease burden are broadly useful for public health, helping national and local authorities monitor epidemiologic trends, plan and allocate resources, and promote influenza vaccination. Historically, estimates of the burden of seasonal influenza in the United States, focused mainly on influenza‐related mortality and hospitalization, were generated every few years. Since the 2010‐2011 influenza season, annual US influenza burden estimates have been generated and expanded to include estimates of influenza‐related outpatient medical visits and symptomatic illness in the community.
Influence of oxygen plasma treatment parameters on the properties of carbon fiber

Abstract This study is focused on the impact of oxygen plasma treatment on properties of carbon fibers and interfacial adhesion behavior between the carbon fibers and epoxy resin. The influences of the main parameters of plasma treatment process, including duration, power, and flow rate of oxygen gas were studied in detail using interlaminar shear strength (ILSS) of carbon fiber composites. The ILSS of composites made of carbon fibers treated by oxygen plasma for 1 min, at power of 125 W, and oxygen flow rate of 100 sccm presented a maximum increase of 28% compared to composites made of untreated carbon fibers. Furthermore, carbon fibers were characterized by scanning electron microscopy (SEM), tensile strength test, attenuated total reflectance Fourier transform infrared (ATR-FTIR), and Raman spectroscopy analyses. It was found that the concentration of reactive functional groups on the fiber surface was increased after the plasma modification, as well the surface roughness, which finally improved the interfacial adhesion between carbon fibers and epoxy resin. However, high power and long exposure times could partly damage the surface of carbon fibers and decrease the tensile strength of filaments and ILSS of treated fiber composites.
Preparation and characterization of polylactic acid based polyurethane for environmental friendly packaging materials

Conventional packaging materials are mostly produced using petroleum-based substances and its’ non-biodegradability are causing landfill problems. Therefore, researches have been done to replace the non-degradable polymer substances to degradable polymers. Polylactic acid (PLA) is a type of biodegradable polymer which is brittle but has good mechanical strength, which makes it a suitable polymer to be used as packaging materials. To improve the flexibility of PLA, PLA based polyurethanes (PUs) are produced by using PLA-diol with vegetable oil polyol as the chain extender. Palm oil polyol (PO) is a type of vegetable oil polyol which are used in various productions of PUs. In this study, PO polyol is used as soft segment to improve the flexibility of PLA whereas hexamethylene diisocyanate (HDI) and toluene diisocyanate (TDI) are used as a source of isocyanate. PLA/Palm oil polyol based polyurethanes (PLAPOPUs) are synthesized using one-shot and two steps polymerization method. Fourier Transform Infra-Red (FT-IR) spectra confirmed on the formation of urethane bond and glass transition temperature was analyzed using Differential Scanning Calorimetry (DSC). The PLAPOPU prepared using HDI through one-step method has high potential to be used in environmental friendly packaging industries.
APOEε4 and slow wave sleep in older adults

Slow wave (or stage N3) sleep has been linked to a variety of cognitive processes. However, the role of stage N3 in the elderly is debated. The link between stage N3 and episodic memory may be weakened or changed in the older adult population, possibly due to several altered mechanisms impacting the cellular structure of the brain. The bases for the age-related dissociation between stage N3 and cognition are not understood. Since APOEε4 status is the strongest genetic risk factor for cognitive decline, we assessed whether the ε4 allele is associated with stage N3 sleep. Participants were from the population-based Osteoporotic Fractures in Men (MrOS) cohort with polysomnography and APOEε4 genotype data (n = 2,302, 100% male, mean age 76.6 years). Sleep stages were objectively measured using overnight in-home polysomnography and central electroencephalogram data were used to score stage N3 sleep. Cognitive function was assessed using the Modified Mini Mental State Exam (3MS). The APOE rs429358 single nucleotide polymorphism, which defines the APOEε4 allele, was genotyped using a custom genotyping array. Total time in stage N3 sleep was significantly higher (p<0.0001) among the 40 MrOS participants carrying two copies of the ε4 allele (62±5.2 minutes) compared with 43±1.5 minutes for carriers of one ε4 allele (n = 515) and 40±0.8 minutes for ε4 non-carriers (n = 1747). All results were independent of sleep efficiency, number of sleep cycles, and apnea hypopnea index. These findings support an association between APOEε4 genotype and sleep stage N3 in the elderly. Increased total stage N3 duration among ε4/ε4 carriers does not appear to reflect compensation for prior cognitive decline and may reflect overactive downscaling of synapses during sleep. If confirmed, these results might in part explain the high risk of age-related cognitive decline and AD among APOE ε4/ε4 carriers.
Primary Care–Based Skin Cancer Screening in a Veterans Affairs Health Care System

Importance Skin cancer screening may improve melanoma outcomes and keratinocyte carcinoma morbidity, but little is known about the feasibility of skin cancer training and clinical skin examination (CSE) by primary care practitioners (PCPs) in large health care systems. Objective To assess the association of skin cancer training and screening by PCPs with dermatology referral patterns and rates of skin biopsies. Design, Setting, and Participants In this pilot interventional study performed at the Veterans Affairs Palo Alto Health Care System, patients 35 years or older scheduled for an annual health habits screen in the PCP general medicine clinics were studied. Interventions Six PCPs underwent Internet Curriculum for Melanoma Early Detection (INFORMED) training in May 2015, and 5 screened patients during the following 14 months. Main Outcomes and Measures Proportion of dermatology referrals, subsequent skin biopsies, and PCP diagnostic accuracy for skin cancer or precancer compared with dermatologist diagnosis were assessed in screened patients 14 months before the intervention (February 18, 2014, through April 30, 2015) and after the intervention (June 18, 2015, through August 30, 2016). Results Among 258 patients offered screening (median age, 70 years; age range, 35-94 years; 255 [98.8%] male), 189 (73.3%) received CSE and 69 (26.7%) declined. A total of 62 of 189 patients (32.8%) were referred to a dermatologist after intervention: 33 (53.2%) for presumptive skin cancers and 15 (24.2%) for precancers. Nine of 50 patients (18.0%) evaluated in dermatology clinic underwent biopsy to exclude skin cancer. Correct diagnoses were made by PCPs in 13 of 38 patients (34.2%; 4 of 27 patients [14.8%] diagnosed with skin cancers and 5 of 11 patients [45.5%] diagnosed with actinic keratoses). Comparison of all outpatient visits for the 5 main participating PCPs before vs after intervention revealed no significant differences in dermatology referrals overall and those for presumptive skin cancer or actinic keratoses, skin biopsies, or PCP diagnostic accuracy with the exception of significantly fewer postintervention dermatology referrals that lacked specific diagnoses (25 [1.0%] vs 10 [0.4%], P = .01). Conclusions and Relevance This pilot study suggests that PCP-based skin cancer training and screening are feasible and have the potential to improve PCP diagnostic accuracy without increasing specialty referrals or skin biopsies. Additional studies comparing screening rates, specialty referrals, and patient outcomes in trained vs untrained PCPs are needed before screening is widely implemented in large health care systems in the United States.
Behavioral Adjustment Moderates the Link Between Neuroticism and Biological Health Risk: A U.S.–Japan Comparison Study

Neuroticism, a broad personality trait linked to negative emotions, is consistently linked to ill health when self-report is used to assess health. However, when health risk is assessed with biomarkers, the evidence is inconsistent. Here, we tested the hypothesis that the association between neuroticism and biological health risk is moderated by behavioral adjustment, a propensity to flexibly adjust behaviors to environmental contingencies. Using a U.S.–Japan cross-cultural survey, we found that neuroticism was linked to lower biological health risk for those who are high, but not low, in behavioral adjustment. Importantly, Japanese were higher in behavioral adjustment than European Americans, and as predicted by this cultural difference, neuroticism was linked to lower biological health risk for Japanese but not for European Americans. Finally, consistent with prior evidence, neuroticism was associated with worse self-reported health regardless of behavioral adjustment or culture. Discussion focused on the significance of identifying sociocultural correlates of biological health.
The Neural Dynamics of Facial Identity Processing: Insights from EEG-Based Pattern Analysis and Image Reconstruction

Abstract Uncovering the neural dynamics of facial identity processing along with its representational basis outlines a major endeavor in the study of visual processing. To this end, here, we record human electroencephalography (EEG) data associated with viewing face stimuli; then, we exploit spatiotemporal EEG information to determine the neural correlates of facial identity representations and to reconstruct the appearance of the corresponding stimuli. Our findings indicate that multiple temporal intervals support: facial identity classification, face space estimation, visual feature extraction and image reconstruction. In particular, we note that both classification and reconstruction accuracy peak in the proximity of the N170 component. Further, aggregate data from a larger interval (50–650 ms after stimulus onset) support robust reconstruction results, consistent with the availability of distinct visual information over time. Thus, theoretically, our findings shed light on the time course of face processing while, methodologically, they demonstrate the feasibility of EEG-based image reconstruction.
A hypothesis for temporal coding of young and mature granule cells

While it has been hypothesized that adult neurogenesis (NG) plays a role in the encoding of temporal information at long time-scales, the temporal relationship of immature cells to the highly rhythmic network activity of the hippocampus has been largely unexplored. Here, we present a theory for how the activity of immature adult-born granule cells relates to hippocampal oscillations. Our hypothesis is that theta rhythmic (5–10 Hz) excitatory and inhibitory inputs into the hippocampus could differentially affect young and mature granule cells due to differences in intrinsic physiology and synaptic inhibition between the two cell populations. Consequently, immature cell activity may occur at broader ranges of theta phase than the activity of their mature counterparts. We describe how this differential influence on young and mature granule cells could separate the activity of differently aged neurons in a temporal coding regime. Notably, this process could have considerable implications on how the downstream CA3 region interprets the information conveyed by young and mature granule cells. To begin to investigate the phasic behavior of granule cells, we analyzed in vivo recordings of the rat dentate gyrus (DG), observing that the temporal behavior of granule cells with respect to the theta rhythm is different between rats with normal and impaired levels of NG. Specifically, in control animals, granule cells exhibit both strong and weak coupling to the phase of the theta rhythm. In contrast, the distribution of phase relationships in NG-impaired rats is shifted such that they are significantly stronger. These preliminary data support our hypothesis that immature neurons could distinctly affect the temporal dynamics of hippocampal encoding.
A General Cognitive Architecture for Agent-Based Modeling in Artificial Societies

Artificial Society is an analytical foundation of various complex eco- and social systems. Such system is usually implemented via multiagent approach. However, there is no consensus on how to model the agent’s decision-making process, since different application scenarios concentrate on different facets. This, to some extent, hinders model reuse and system integration. This paper proposes a general cognitive architecture that attempts to adapt all the aspects of agent’s decision-making in artificial societies, so that different programs and software can be reorganized and integrated conveniently. To illustrate its implementation, two simulations—emergent evacuation and population evolution—are conducted. These tests clearly show that the proposed architecture is able to support different agent-based models. Problems that might be encountered, as well as possible strategies, are also proposed in the end.
Intra‐operative evaluation of prophylactic hysterectomy and salpingo‐oophorectomy specimens in hereditary gynaecological cancer syndromes

Prophylactic total hysterectomy (TH) and bilateral salpingo‐oophorectomy (BSO) have become routine procedures in women at genetic risk for gynaecological malignancies. Intra‐operative pathology diagnosis of an occult malignancy provides the opportunity for immediate surgical staging and helps to avoid a second surgery. However, no standard guidelines exist for optimal intra‐operative evaluation (IOE) of these specimens. We performed a retrospective analysis of prophylactic TH and BSO cases to assess the presence of gross findings, frozen and permanent section sampling practices, frozen section diagnoses and diagnostic discrepancies.
Characterization of Peroxidase Changes in Tolerant and Susceptible Soybeans Challenged by Soybean Aphid (Hemiptera: Aphididae)

ABSTRACT Changes in protein content, peroxidase activity, and isozyme profiles in response to soybean aphid feeding were documented at V1 (fully developed leaves at unifoliate node, first trifoliate leaf unrolled) and V3 (fully developed leaf at second trifoliate node, third trifoliate leaf unrolled) stages of soybean aphid-tolerant (KS4202) and -susceptible (SD76R) soybeans. Protein content was similar between infested and control V1 and V3 stage plants for both KS4202 and SD76R at 6, 16, and 22 d after aphid introduction. Enzyme kinetics studies documented that control and aphid-infested KS4202 V1 stage and SD76R V1 and V3 stages had similar levels of peroxidase activity at the three time points evaluated. In contrast, KS4202 aphid-infested plants at the V3 stage had significantly higher peroxidase activity levels than control plants at 6 and 22 d after aphid introduction. The differences in peroxidase activity observed between infested and control V3 stage KS4202 plants at these two time points suggest that peroxidases may be playing multiple roles in the tolerant plant. Native gels stained for peroxidase were able to detect differences in the isozyme profiles of aphidinfested and control plants for both KS4202 and SD76R.
Improved Stable Isotope Dilution Assay for Dietary Folates Using LC-MS/MS and Its Application to Strawberries

Folates play an important role in the human body and a deficiency of this vitamin can cause several diseases. Therefore, a reliable analytical method is crucial for the determination of folate vitamers in strawberries and other dietary folate sources. A stable isotope dilution LC-MS/MS method for analyzing folates in food was developed and validated. The folate vitamers Pteroylmonoglutamic acid, tetrahydrofolate, 5-methyltetrahydrofolate, and 5-formyltetrahydrofolate were quantified using 13C-labeled internal standards. Validation of the assay was accomplished by determining linearity, precision, recovery, limit of detection, and limit of quantification and revealed to be a precise, sensitive, and accurate method to determine folate vitamers. Strawberries are worldwide consumed and known to be a good dietary source of nutritive compounds. Using this method, folate concentrations in selected commercial strawberry cultivars and experimental breeding lines grown in Germany and Australia were investigated. Total folates varied from 59 to 153 μg/100 g on fresh weight basis. Furthermore, folate content after lyophilizing or freezing did not show any significant differences compared to fresh strawberries. However, significant losses of total folates in pureed strawberries could be observed after 5 days of storage with only 16% of the original concentration retained. In summary, some of the investigated strawberry cultivars/breeding lines can be considered as rich dietary sources of natural folates.
In Pursuit of “queer-friendly” Healthcare: An Interview Study of How Queer Individuals Select Care Providers

ABSTRACT LGBQ+ individuals experience worse health outcomes than do other individuals. Some communication research finds that LGBQ+ individuals report receiving poor care during the mid- to post-health care, but this research assumes that LGBQ+ individuals have already received care. Little research has examined the pre- to early encounter experience of LGBQ+ individuals. This study presents exploratory research into how LGBQ+ individuals seek “queer-friendly” health care during pre- and early encounter experiences. Using an interview methodology, we report the facilitators and barriers to seeking queer-friendly care reported by LGBQ+ individuals. We offer implications for how health care providers and systems can better promote queer-friendly healthcare.