Miracle-dz/UniFAR-FTUs huggingface dataset:
Models of Inflammation: Carrageenan‐ or Complete Freund's Adjuvant (CFA)–Induced Edema and Hypersensitivity in the Rat

Animal models of inflammation are used to assess the production of inflammatory mediators at sites of inflammation, the processing of pain sensation at CNS sites, the anti‐inflammatory properties of agents such as nonsteroidal anti‐inflammatory drugs (NSAIDs), and the efficacy of putative analgesic compounds in reversing cutaneous hypersensitivity. Detailed in this article are methods to elicit and measure carrageenan‐ and complete Freund's adjuvant (CFA)–induced cutaneous inflammation. Due to possible differences between the dorsal root sensory system and the trigeminal sensory system, injections into either the footpad or vibrissal pad are described. In this manner, cutaneous inflammation can be assessed in tissue innervated by the lumbar dorsal root ganglion neurons (footpad) or by the trigeminal ganglion neurons (vibrissal pad). © 2021 Wiley Periodicals LLC.
Random control selection for conducting high‐throughput adverse drug events screening using large‐scale longitudinal health data

Case‐control design based high‐throughput pharmacoinformatics study using large‐scale longitudinal health data is able to detect new adverse drug event (ADEs) signals. Existing control selection approaches for case‐control design included the dynamic/super control selection approach. The dynamic/super control selection approach requires all individuals to be evaluated at all ADE case index dates, as the individuals’ eligibilities as control depend on ADE/enrollment history. Thus, using large‐scale longitudinal health data, the dynamic/super control selection approach requires extraordinarily high computational time. We proposed a random control selection approach in which ADE case index dates were matched by randomly generated control index dates. The random control selection approach does not depend on ADE/enrollment history. It is able to significantly reduce computational time to prepare case‐control data sets, as it requires all individuals to be evaluated only once. We compared the performance metrics of all control selection approaches using two large‐scale longitudinal health data and a drug‐ADE gold standard including 399 drug‐ADE pairs. The F‐scores for the random control selection approach were between 0.586 and 0.600 compared to between 0.545 and 0.562 for dynamic/super control selection approaches. The random control selection approach was ~ 1000 times faster than dynamic/super control selection approach on preparing case‐control data sets. With large‐scale longitudinal health data, a case‐control design‐based pharmacoinformatics study using random control selection is able to generate comparable ADE signals than the existing control selection approaches. The random control selection approach also significantly reduces computational time to prepare the case‐control data sets.
Stress response asymmetries in African American emerging adults exposed to chronic social adversity

Abstract Chronic stress is linked to social adversity and underlies many health disparities among ethnic minorities. Cortisol and salivary alpha-amylase (sAA) reflect sensitivity to adversity and are related to health outcomes. Our aim was to understand how social adversity influences biological responses to experimental and daily stressors in a sample of low-income African American emerging adults. In the three-week study, participants completed questionnaires, the Trier Social Stress Task (TSST), and provided four salivary samples. In week 2, participants collected saliva at home immediately after waking and just before bed for three days. Results demonstrated an asymmetrical pattern between cortisol and sAA reactivity that was related to experiences with racism and interpersonal trauma. Further, daily stress was related to lower morning and higher nighttime cortisol, indicating atypical diurnal rhythm. These findings are consistent with other forms of social adversity that lead to long-term changes in the HPA axis response pattern. LAY SUMMARY African American emerging adults showed divergent cortisol and sAA responses. Social adversity predicted an asymmetrical response pattern for sAA and cortisol. Atypical diurnal rhythms were found for participants reporting high daily stress.
Engaging Diverse Older Adults With Cognitive Impairment and Caregivers in Advance Care Planning

Supplemental Digital Content is available in the text. Introduction: Engaging patients with cognitive impairment in advance care planning (ACP), including completing advance directives and naming health care proxies, before they lose decision-making capacity is important. Methods: We determined the feasibility of the PREPAREforYourCare.org ACP program among 20 diverse older adults with mild-to-moderate cognitive impairment and their caregivers in a 1-week, pre-post pilot. We examined ease-of-use, satisfaction, and feasibility using validated scales, and change in ACP Engagement scores, including knowledge, contemplation, self-efficacy, and readiness subscales (5-point scales), from baseline to 1-week. Results: Participants were on average 70 years old (SD=9.0), 45% Spanish-speaking, 60% had limited health literacy, and 15% felt comfortable using the internet. Patients and caregivers rated PREPARE a mean of 8.6 (SD=1.6) and 9.4 (SD=1.1) on the 10-point ease-of-use scale, 4.7 (SD=0.4) and 4.7 (SD=0.3) on the 5-point satisfaction scale, and 4.9 (SD=0.4) and 4.8 (SD=0.6) on the 5-point feasibility scale, respectively. ACP engagement scores increased for 16 of 20 (80%) patients (P=0.03) and 16 of 20 (80%) caregivers (P=0.18). Caregivers experienced increased knowledge (3.8 to 4.7, P=0.002) and self-efficacy (3.6 to 4.5, P=0.034) for ACP. Discussion: The PREPARE website was feasible and may facilitate ACP engagement among diverse older adults with cognitive impairment and their caregivers.
Oblique lateral interbody fusion to treat lumbar spinal stenosis in a patient with situs inversus totalis: a case report

Oblique lateral interbody fusion (OLIF) is a minimally invasive spinal surgery that is popular for lumbar degeneration and spinal deformity treatment because it causes minimal damage to the stability of the intervertebral structures. However, when encountering abnormal anatomical structures caused by situs inversus, surgical routes must be adjusted to avoid serious complications. A 42-year-old woman with lumbar spinal stenosis presented to our hospital. Preoperative X-ray and computed tomography indicated situs inversus totalis, with the abdominal aorta and inferior vena cava reversed. We established an appropriate surgical approach for OLIF via the right abdomen according to the characteristics of the anatomical structures. Postoperative X-rays showed adequate positioning of the interbody fusion cage and internal fixation screws. At the 3-month follow-up, the patient reported resolution of her symptoms. Vascular variations caused by situs inversus totalis can affect the course of OLIF. Understanding the unique anatomical structure in such patients is crucial for successful surgery and to avoid intraoperative complications.
Discovery-stage identification of drug-like antibodies using emerging experimental and computational methods

ABSTRACT There is intense and widespread interest in developing monoclonal antibodies as therapeutic agents to treat diverse human disorders. During early-stage antibody discovery, hundreds to thousands of lead candidates are identified, and those that lack optimal physical and chemical properties must be deselected as early as possible to avoid problems later in drug development. It is particularly challenging to characterize such properties for large numbers of candidates with the low antibody quantities, concentrations, and purities that are available at the discovery stage, and to predict concentrated antibody properties (e.g., solubility, viscosity) required for efficient formulation, delivery, and efficacy. Here we review key recent advances in developing and implementing high-throughput methods for identifying antibodies with desirable in vitro and in vivo properties, including favorable antibody stability, specificity, solubility, pharmacokinetics, and immunogenicity profiles, that together encompass overall drug developability. In particular, we highlight impressive recent progress in developing computational methods for improving rational antibody design and prediction of drug-like behaviors that hold great promise for reducing the amount of required experimentation. We also discuss outstanding challenges that will need to be addressed in the future to fully realize the great potential of using such analysis for minimizing development times and improving the success rate of antibody candidates in the clinic.
Glass, Gel, and Liquid Crystals: Arrested States of Graphene Oxide Aqueous Dispersions

Colloidal systems with competing interactions are known to exhibit a range of dynamically arrested states because of the systems’ inability to reach its underlying equilibrium state due to intrinsic frustration. Graphene oxide (GO) aqueous dispersions constitute a class of 2D-anisotropic colloids with competing interactions—long-range electrostatic repulsion, originating from ionized groups located on the rim of the sheets, and weak dispersive attractive interactions originating from the unoxidized graphitic domains. We show here that aqueous dispersions of GO exhibit a range of arrested states, encompassing fluid, glass, and gels that coexist with liquid-crystalline order with increasing volume fraction. These states can be accessed by varying the relative magnitudes of the repulsive and attractive forces. This can be realized by changing the ionic strength of the medium. We observe at low salt concentrations, where long-range electrostatic repulsion dominates, the formation of a repulsive Wigner glass, .
Room-Temperature Ordered Spin Structures in Cluster-Assembled Single V@Si12 Sheets

Since most of the existing pristine two-dimensional (2D) materials are either intrinsically nonmagnetic or magnetic with small magnetic moment per unit cell and weak strength of magnetic coupling, introducing transition metal atoms in various nanosheets has been widely used for achieving a desired 2D magnetic material. However, the problem of surface clustering for the doped transition metal atoms is still challenging. Here we demonstrate via first-principles calculations that the recently experimentally characterized endohedral silicon cage V@Si12 clusters can construct two types of single cluster sheets exhibiting hexagonal porous or honeycomb-like framework with regularly and separately distributed V atoms. For the ground state of these two sheets, the preferred magnetic coupling is found to be ferromagnetic due to a free-electron-mediated mechanism. By using external strain, the magnetic moments and strength of magnetic coupling for these two sheets can be deliberately tuned, which would be propitious.
Iodine Status of Canadian Children, Adolescents and Women of Childbearing Age.

BACKGROUND Adequate iodine intake is important for children and women of childbearing age because iodine is vital for fetal brain development and early life. OBJECTIVE Iodine status of children (n = 1875), adolescents (n = 557) and women of childbearing age (n = 567) was assessed using urinary iodine concentrations (UIC) from duplicate spot samples collected in the Canadian Health Measures Survey, cycle 5 (2016 - 2017). METHODS Daily iodine intakes were estimated from urinary iodine and creatinine concentrations using a formula based on iodine absorption and predicted 24-h creatinine excretion. Usual UIC and iodine intakes, adjusted for within-person variation, were estimated using the National Cancer Institute method. Iodine status was assessed by (1) comparing median UIC with WHO/UNICEF/ICCIDD reference ranges and (2) estimating the prevalence of inadequate and excessive intakes using the Estimated Average Requirement (EAR) and Tolerable Upper Intake Level (UL) cut-point method, respectively. RESULTS Median UIC for males or females 6 - 11 y or 12 - 19 y were ≥100 µg/L, the lower cut-off for adequate intakes. For women 20 - 39 y, median UIC (95% CI) of an unadjusted sample was 81 µg/L (67, 95) and for usual UIC 108 µg/L (84, 131). Percentage of children 3 y with iodine intakes ≥ EAR was 82% (75, 89). The corresponding estimates for males 4 - 8 y, 9 - 13 y and 14 - 18 y were 93% (88, 97), 91% (87, 96) and 84% (76, 91), respectively. Estimates for females were 4 - 8 y 86% (83, 89), 9 - 13 y 87% (80, 95), 14 - 18 y 68% (55, 80) and 19 - 39 y 68% (59, 76). For all sex-age groups, 91 - 100% had iodine intakes ≤ UL. CONCLUSIONS Iodine intakes may be insufficient for some women of childbearing age. Public health policies and programs should continue to recommend that all women who could become pregnant, or women who are pregnant or breastfeeding, take a daily multivitamin-mineral supplement containing iodine.
Demographically-corrected normative data for the RBANS learning ratio in a sample of older adults

Abstract Background A novel learning slope score – the Learning Ratio (LR) – has recently been developed that appears to be sensitive to memory performance and AD pathology more optimally than traditional learning slope calculations. While promising, this research to date has been both experimental and based on group differences, and therefore does not aid in the interpretation of individual LR performance for either clinical or research settings. The objective of the current study was to develop demographically-corrected normative data on these LR learning slopes on verbal learning measures from the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Method The current study examined the influence of age and education on LR metrics for the List Learning, Story Memory, and an Aggregated RBANS score in 200 cognitively intact adults aged 65 or older using linear regression. Results Age and education correlated with most LR metrics, but no sex differences were observed. Linear regression permitted the prediction of LR values from age and education, which are then compared to observed LR values. The result is demographically-corrected T scores for these LR metrics. Conclusions By comparing observed and predicted LR scores calculated from regression-based prediction equations, this represents the first step towards interpretation of individual performances on this metric for clinical decision making and treatment planning purposes. With future replication in diverse and heterogenous samples, we hope to offer a new clinical tool for the examination of learning slopes in older adults.
Co-circulation of multiple influenza A reassortants in swine harboring genes from seasonal human and swine influenza viruses

Since the influenza pandemic in 2009, there has been an increased focus on swine influenza A virus (swIAV) surveillance. This paper describes the results of the surveillance of swIAV in Danish swine from 2011 to 2018. In total, 3800 submissions were received with a steady increase in swIAV-positive submissions, reaching 56% in 2018. Full-genome sequences were obtained from 129 swIAV-positive samples. Altogether, 17 different circulating genotypes were identified including six novel reassortants harboring human seasonal IAV gene segments. The phylogenetic analysis revealed substantial genetic drift and also evidence of positive selection occurring mainly in antigenic sites of the hemagglutinin protein and confirmed the presence of a swine divergent cluster among the H1pdm09Nx (clade 1A.3.3.2) viruses. The results provide essential data for the control of swIAV in pigs and emphasize the importance of contemporary surveillance for discovering novel swIAV strains posing a potential threat to the human population.
Chaperonin‐containing tailless complex polypeptide 1 subunit 6A correlates with increased World Health Organization grade, less isocitrate dehydrogenase mutation, and deteriorative survival of astrocytoma patients

Chaperonin‐containing tailless complex polypeptide 1 subunit 6A (CCT6A) is reported to be an efficient prognostic biomarker in various cancers, but it is rarely reported in astrocytoma. Thus, this study aimed to evaluate the expression of CCT6A and its correlation with disease features and prognosis in astrocytoma patients.
Effects of anthropogenic landscapes on population maintenance of waterbirds

Anthropogenic impacts have reduced natural areas but increased the area of anthropogenic landscapes. There is debate about whether anthropogenic landscapes (e.g., farmlands, orchards, and fish ponds) provide alternatives to natural habitat and under what circumstances. We considered whether anthropogenic landscapes can mitigate population declines for waterbirds. We collected data on population trends and biological traits of 1203 populations of 579 species across the planet. Using Bayesian generalized linear mixed models, we tested whether the ability of a species to use an anthropogenic landscape can predict population trends of waterbird globally and of species of conservation concern. Anthropogenic landscapes benefited population maintenance of common but not less‐common species. Conversely, the use of anthropogenic landscapes was associated with population declines for threatened species. Our findings delineate some limitations to the ability of anthropogenic landscapes to mitigate population declines, suggesting that the maintenance of global waterbird populations depends on protecting remaining natural areas and improving the habitat quality in anthropogenic landscapes.
Liquid biopsy: a non‐invasive approach for Hodgkin lymphoma genotyping

The Hodgkin lymphoma (HL) genomic landscape is hardly known due to the scarcity of tumour cells in the tissue. Liquid biopsy employing circulating tumour DNA (ctDNA) can emerge as an alternative tool for non‐invasive genotyping. By using a custom next generation sequencing (NGS) panel in combination with unique molecule identifiers, we aimed to identify somatic variants in the ctDNA of 60 HL at diagnosis. A total of 277 variants were detected in 36 of the 49 samples (73·5%) with a good quality ctDNA sample. The median number of variants detected per patient was five (range 1–23) with a median variant allele frequency of 4·2% (0·84–28%). Genotyping revealed somatic variants in the following genes: SOCS1 (28%), IGLL5 (26%), TNFAIP3 (23%), GNA13 (23%), STAT6 (21%) and B2M (19%). Moreover, several poor prognosis features (high LDH, low serum albumin, B‐symptoms, IPI ≥ 3 or at an advanced stage) were related to significantly higher amounts of ctDNA. Variant detection in ctDNA by NGS is a feasible approach to depict the genetic features of HL patients at diagnosis. Our data favour the implementation of liquid biopsy genotyping for the routine evaluation of HL patients.
Evaluation of a Chronic Pain Screening Program Implemented in Primary Care

Key Points Question What is the utility of using a patient-reported outcome measure to assess chronic pain? Findings In this cross-sectional study of 31 600 patients, 32.5% screened positive for chronic pain with use of a tool comprising a single-question assessment of pain frequency, followed by a 3-question functional assessment (pain, enjoyment of life, and general activity). Of these patients, 43.9% had not received a diagnosis for a chronic painful condition and 59.1% reported severe pain interference with activities of daily living. Meaning The findings of this study suggest that implementing this measure for chronic pain screening and functional assessment might provide additional clinical information on patients’ pain experience.
Visible-Light-Driven Water Oxidation on a Photoanode by Supramolecular Assembly of Photosensitizer and Catalyst.

A ruthenium water oxidation catalyst (WOC) bearing hydrophobic ligands was incorporated on the surface of a dye-sensitized nanostructured TiO2 film by formation of a host-guest adduct with the dye. This provides a new strategy for constructing photocatalytically active electrodes for water oxidation. The resultant photoanode exhibits a photocurrent of 800 μA cm-2 under visible-light illumination (λ>400 nm, 300 mW cm-2 ) and 240 μA cm-2 under simulated sunlight illumination (AM 1.5G, 100 mW cm-2 ) with an applied bias of 0.2 V vs. NHE in neutral phosphate buffer.
An Experimental Study of Indoor and Outdoor Concentrations of Fine Particles Through Nonisothermal Cracks

It has been shown that a substantial proportion of indoor exposure is from particles originating outdoors. Idealized cracks have been used to study penetration under laboratory settings and all previous studies assumed isothermal conditions. There can be 10–20°C difference between indoor and outdoor temperatures even in mild climate zones. This is the first study to investigate the influence of thermophoresis on the penetration of particles through cracks. A sandwich design consisting of two chambers (each 0.325 [W] × 0.125 [L] × 0.11 [H] m3) and a crack module was used to measure indoor-to-outdoor particle concentrations under practical indoor and outdoor conditions. An idealized aluminum smooth crack of 90 mm crack length was tested under three different pressures ranging from 4 to 8 Pa. Submicron sodium chloride particles were generated and a scanning mobility particle sizer was used to scan the concentration in outdoor and indoor chambers. To mimic summer and winter conditions in temperate climatic zones, two sets of temperature differences (indoor–outdoor) were used: +18°C and −10°C. I/O ratio and relative difference of I/O ratio compared to the isothermal condition were calculated. Inferring from the results, it can be observed that the I/O ratios under the winter scenario are substantially higher than those under the summer and isothermal scenarios for particle sizes less than 100 nm and the influence of temperature on I/O ratios diminishes with increasing particle sizes. Copyright 2013 American Association for Aerosol Research
Characterisation of anal intraepithelial neoplasia and anal cancer in HIV‐positive men by immunohistochemical markers p16, Ki‐67, HPV‐E4 and DNA methylation markers

Human papillomavirus (HPV)‐induced anal intraepithelial neoplasia (AIN, graded 1‐3) is highly prevalent in HIV‐positive (HIV+) men who have sex with men (MSM), but only a minority of lesions progresses to cancer. Our study aimed to characterise comprehensively anal tissue samples from a cross‐sectional series (n = 104) of HIV+ MSM and longitudinal series (n = 40) of AIN2/3 progressing to cancer using different biomarkers. The cross‐sectional series consisted of 8 normal, 26 AIN1, 45 AIN2, 15 AIN3 and 10 anal squamous cell carcinoma. Tissue sections were immunohistochemically (IHC) stained for p16 (viral transformation marker), Ki‐67 (cellular proliferation marker) and HPV‐E4 (viral production marker). We evaluated the expression of IHC markers and compared it with DNA methylation, a marker for malignant transformation. E4 positivity decreased, whereas p16 and Ki‐67 scores and methylation marker positivity increased (P values < .001) with increasing severity of anal lesions. Within AIN2, a heterogeneous biomarker pattern was observed concerning E4, p16 and methylation status, reflecting the biological heterogeneity of these lesions. In the longitudinal series, all AIN2/3 and carcinomas showed high p16 and Ki‐67 expression, strong methylation positivity and occasional E4 positivity. We earlier showed that high methylation levels are associated with progression to cancer. The observed E4 expression in some AIN2/3 during the course of progression to cancer and absence of E4 in a considerable number of AIN1 lesions make the potential clinical significance of E4 expression difficult to interpret. Our data show that IHC biomarkers can help to characterise AIN; however, their prognostic value for cancer risk stratification, next to objective methylation analysis, appears to be limited.