Miracle-dz/UniFAR-FTUs huggingface dataset:
Epitope and Fc-Mediated Cross-linking, but Not High Affinity, Are Critical for Antitumor Activity of CD137 Agonist Antibody with Reduced Liver Toxicity

CD137 (TNFRSF9, 4-1BB) agonist antibodies (mAb) have demonstrated potent antitumor activity with memory response while causing hepatotoxicity in mouse models. In clinical trials, the degrees of liver toxicity of anti-CD137 vary from grade 4 transaminitis (urelumab) to nonexistent (utomilumab). To exploit the antitumor potential of CD137 signaling, we identified a new class of CD137 agonist mAbs with strong antitumor potency without significant transaminitis in vivo compared with CD137 agonists previously reported. These mAbs are cross-reactive to mouse and cynomolgus monkey and showed cross-linking–dependent T-cell costimulation activity in vitro. Antitumor efficacy was maintained in Fc gamma receptor (FcγR) III–deficient mice but diminished in FcγRIIB-deficient mice, suggesting the critical role for FcγRIIB to provide cross-linking in vivo. Interestingly, a single dose of an affinity-reduced variant was sufficient to control tumor growth, but a higher affinity variant did not improve efficacy. These observations suggest that binding epitope and FcγR interaction, but not necessarily high affinity, are important for antitumor efficacy and reduced liver toxicity of CD137 mAb. Our study suggests the possibility of CD137 agonist therapy with improved safety profile in humans.
The Prediction of Geocentric Corrections during Communication Link Outages in PPP

The International GNSS Service (IGS) real-time service (RTS) provides access to real-time precise products. State-Space Representation (SSR) products are disseminated through the Internet using the Networked Transport of the RTCM (Radio Technical Commission for Maritime Services) via the Internet Protocol (NTRIP). However, communication outages caused by a loss of the communication link during ephemeris changes can occur. Unfortunately, any break in providing orbit and clock corrections affects the possibility to perform precise point positioning. To eliminate this problem, various methods have been developed and presented in the literature. The solution proposed by the authors is to directly predict geocentric corrections. This manuscript presents the results and analysis of geocentric correction predictions under two scenarios: the first between the IODE (issue of data ephemeris) value change and the second where prediction must be done for epochs containing a change in IODE ephemeris. In this case, the prediction uses data from a previous message. The Root Mean Square (RMS) values calculated based on the differences between the true correction values and the predicted geocentric corrections using a linear function, a second-degree polynomial and a constant value do not differ significantly. The numerical results show that, in most cases, maintaining the constant value of the last registered SSR correction is the best option.
The metastable XBP1u transmembrane domain defines determinants for intramembrane proteolysis by signal peptide peptidase

Unspliced XBP1 mRNA encodes XBP1u, the transcriptionally inert variant of the unfolded protein response (UPR) transcription factor XBP1s. XBP1u targets its mRNA-ribosome-nascent-chain-complex to the endoplasmic reticulum (ER) to facilitate UPR activation and prevents overactivation. Yet, its membrane association is controversial. Here, we use cell-free translocation and cellular assays to define a moderately hydrophobic stretch in XBP1u that is sufficient to mediate insertion into the ER membrane. Mutagenesis of this transmembrane (TM) region reveals residues that target XBP1u for an ER-associated degradation route that is initiated by the signal peptide peptidase (SPP). Furthermore, the impact of these mutations on TM helix dynamics was assessed by residue-specific amide exchange kinetics, evaluated by a semi-automated algorithm. Based on our results, we suggest that SPP-catalyzed intramembrane proteolysis of TM helices is not only determined by their conformational flexibility, but also by side chain interactions near the scissile peptide bond with the enzyme’s active site.
Research progress on the etiology and pathogenesis of adolescent idiopathic scoliosis

Abstract Etiology of adolescent idiopathic scoliosis (AIS), a complicated three-dimensional spinal deformity with early-onset, receives continuous attention but remains unclear. To gain an insight into AIS pathogenesis, this review searched PubMed database up to June 2019, using key words or medical subject headings terms including “adolescent idiopathic scoliosis,” “scoliosis,” “pathogenesis,” “etiology,” “genetics,” “mesenchymal stem cells,” and their combinations, summarized existing literatures and categorized the theories or hypothesis into nine aspects. These aspects include bone marrow mesenchymal stem cell studies, genetic studies, tissue analysis, spine biomechanics measurements, neurologic analysis, hormone studies, biochemical analysis, environmental factor analysis, and lifestyle explorations. These categories could be a guidance for further etiology or treatment researches to gain inspiration.
Gene Therapy Approaches to Functional Cure and Protection of Hematopoietic Potential in HIV Infection

Although current antiretroviral drug therapy can suppress the replication of human immunodeficiency virus (HIV), a lifelong prescription is necessary to avoid viral rebound. The problem of persistent and ineradicable viral reservoirs in HIV-infected people continues to be a global threat. In addition, some HIV-infected patients do not experience sufficient T-cell immune restoration despite being aviremic during treatment. This is likely due to altered hematopoietic potential. To achieve the global eradication of HIV disease, a cure is needed. To this end, tremendous efforts have been made in the field of anti-HIV gene therapy. This review will discuss the concepts of HIV cure and relative viral attenuation and provide an overview of various gene therapy approaches aimed at a complete or functional HIV cure and protection of hematopoietic functions.
Risk-sensitive foraging does not explain condition-dependent choices in settling reef fish larvae

The transition from the planktonic larval to the benthic adult stage in reef fishes is perilous, and involves decisions about habitat selection and group membership. These decisions are consequential because they are essentially permanent (many fish rarely leave their initial settlement habitat, at least for the first several days or weeks). In one common Caribbean reef fish, the bluehead wrasse (Thalassoma bifasciatum), settling larvae either join groups or remain solitary. Grouped fish have lower mortality rates but slightly slower growth rates, and fish that are smaller at the time of settlement are less likely to join groups. We hypothesized that the decision of smaller (i.e., lower condition) fish to remain solitary could be explained by risk-sensitive foraging: with less competition, solitary fish may have higher variance in foraging success, so that there is a chance of a high payoff (outweighing the increased mortality risk) despite the lack of a large difference in the average outcome. We tested this by comparing the mean, standard deviation, and maximum number of (a) prey items in stomach contents and (b) post-settlement growth rates (from otolith measurements) of solitary and grouped fish during two settlement pulses on St. Croix, US Virgin Islands. However, we did not find evidence to support our hypothesis, nor any evidence to support the earlier finding that fish in groups have lower average growth rates. Thus we must consider alternative explanations for the tendency of smaller fish to remain solitary, such as the likely costs of searching for and joining groups at the time of settlement. This study reinforces the value of larval and juvenile fish as a testbed for behavioral decisionmaking, because their recent growth history is recorded in their otoliths.
Self-perceived occupational performance of community-dwelling adults living with stroke

Background. Stroke has long-term consequences for functional performance of daily activities. Evaluating client-perceived occupational performance provides insight for designing stroke-specific programs supporting home and community participation. Purpose. This study describes the personal characteristics and self-perceived occupational performance in community-dwelling adults with stroke. Method. A retrospective chart review was undertaken of 25 stroke survivors who sought services at a community-based centre. The outcome measures were the Canadian Occupational Performance Measure (COPM) to evaluate self-perceived occupational performance and the Montreal Cognitive Assessment (MoCA) to screen for cognitive impairment. The analysis used descriptive statistics. Findings. Mean participant age was 64 years, and most participants were Caucasian males (72%). The mean cognitive function score was 22.1 on MoCA, and the mean COPM performance and satisfaction subscores were 4.1 and 3.9, respectively. The top three challenging daily activities were driving, seeking employment, and functional mobility. Implications. Stroke-specific community programs should emphasize the diverse performance concerns important to stroke survivors.
Error Detection and Cost Savings With an Image-Based Workflow Management System Connected to a Computerized Prescription Order Entry Program for Antineoplastic Compounding

Objective The aim of the study was to analyze both the prevalence of errors with the implementation of an image-based workflow management system during the antineoplastic compounding process, and the estimated costs associated with the negative clinical outcome if the errors had not been intercepted. Methods Three months after the implementation of Phocus Rx system at a hospital pharmacy department, the identification, classification (type, preparation stage, and cause), and potential severity degree (from negligible to catastrophic) of the errors intercepted were determined. The probability of an error causing an adverse event if it had reached the patient (from nil [0] to high [0.6]) and its consequences was estimated by a team of clinical pharmacists and physicians. Cost-effectiveness analysis from the hospital’s perspective was performed. Results Overall, 9872 antineoplastic medications were prepared using Phocus Rx. The total compounding error rate was 0.8% (n = 78, 56 [69.2%] were related to incorrect dose, 20 [28.2%] to incorrect drug preparation or conditioning technique, and 2 [2.6%] were wrong drugs). Approximately 70% of the detected errors were classified as undetectable via the previous verification practice, with 11.55% judged to be potentially severe (n = 9) and 51.3% moderate (n = 29). Likelihood of occurrence of an adverse event was medium (0.4) to high (0.6) for 37.2% of the errors. Estimated cost ratio and return on investment were €4.21 and 321%, respectively. Conclusions The implementation of Phocus Rx prevented antineoplastic preparation errors that would have reached the patient otherwise. In addition, acquisition of this technology was estimated to be cost-effective.
The utility of wearable fitness trackers and implications for increased engagement: An exploratory, mixed methods observational study

Objective To explore which features of wearable fitness trackers are used and deemed helpful. Methods Forty-seven participants took part in an online survey. All participants were over 18 years of age and owned a wearable device that objectively measured physical activity and provided feedback. The survey included questions related to the acceptance of different features of wearables, and exercise information, self-efficacy, exercise identity, motivation, and general demographics of the wearer. Seven participants took part in focus groups in an effort to gain further insight into the acceptability and utilization of wearables. Data were examined using means and frequencies. Results Participants were mostly young adults (18–24 years, 48.9%), White (63.8%), female (80.9%), overweight (body mass index 26.0±6.2), students (42.6%) and generally healthy. Fitbit was the most commonly owned wearable device (42.6%). Most participants had owned their device for 6–12 months (27.7%) and they wore their device daily (80.9%). The most commonly used features were rewards/badges (59.6%), notifications (52.2%), and challenges (42.6%). The features that were reportedly the most helpful, however, were motivational cues (83.3%), general health information (82.4%), and challenges (75.0%). Conclusions The reported use and helpfulness ratings of various features of wearables appeared to vary based on the wearer’s gender, race/ethnicity, exercise goal, exercise proficiency, preferred type of exercise, and psychosocial metrics but the results are inconclusive. Future research should evaluate whether engagement with certain features is strongly associated with improved outcomes and whether the use of these features is significantly associated with wearer characteristics.
The Association between Spousal Education and Cognitive Ability among Older Mexican Adults.

OBJECTIVES Education and cognition are closely associated, yet the role of spousal education is not well understood. We estimate the independent effects of own and spousal education on cognitive ability in late-life in Mexico, a developing country experiencing rapid aging. METHODS We analyzed 4,017 married dyads (age 50+) from the 2012 Mexican Health and Aging Study. Cognitive ability for married adults was a factor score from a single factor model. Using seemingly unrelated regression, we test whether spousal education influences older adults' cognitive ability, whether associations are explained by couple-level socioeconomic position, health and health behaviors, and social support, and whether associations differed by gender. RESULTS Education and cognitive ability were correlated within couples. Higher spousal education was associated with better cognitive ability. Associations between spousal education and cognitive ability were independent of own education, did not differ by gender, and remained significant even after adjustment for couple-level socioeconomic position, health and health behaviors, and perceived social support.
Preparation, characterization and preliminary pharmacokinetic study of pH‐sensitive Hydroxyapatite/Zein nano‐drug delivery system for doxorubicin hydrochloride

Zein nanoparticles (Zein NPs) were used as a hydroxyapatite (HA) biomineralization template to generate HA/Zein NPs. Doxorubicin hydrochloride (DOX) was loaded on HA/Zein NPs (HA/Zein‐DOX NPs) to improve its pH‐sensitive release, bioavailability and decrease cardiotoxicity.
Fat and Fat-Free Mass of Preterm and Term Infants from Birth to Six Months: A Review of Current Evidence

To optimize infant nutrition, the nature of weight gain must be analyzed. This study aims to review publications and develop growth charts for fat and fat-free mass for preterm and term infants. Body composition data measured by air displacement plethysmography (ADP) and dual energy X-ray absorptiometry (DXA) in preterm and term infants until six months corrected age were abstracted from publications (31 December 1990 to 30 April 2019). Age-specific percentiles were calculated. ADP measurements were used in 110 studies (2855 preterm and 22,410 term infants), and DXA was used in 28 studies (1147 preterm and 3542 term infants). At term age, preterm infants had higher percent-fat than term-born infants (16% vs. 11%, p < 0.001). At 52 weeks postmenstrual age (PMA), both reached similar percent-fat (24% vs. 25%). In contrast, at term age, preterm infants had less fat-free mass (2500 g vs. 2900 g) by 400 g. This difference decreased to 250 g by 52 weeks, and to 100 g at 60 weeks PMA (5000 g vs. 5100 g). DXA fat-free mass data were comparable with ADP. However, median percent-fat was up to 5% higher with DXA measurements compared with ADP with PMA > 50 weeks. There are methodological differences between ADP and DXA measures for infants with higher fat mass. The cause of higher fat mass in preterm infants at term age needs further investigation.
Position statement by Experts of the Polish Menopause and Andropause Society, and the Polish Society of Aesthetic and Reconstructive Gynaecology on the medicinal product Intrarosa®

A set of menopause-related symptoms affecting the external genitalia and lower urinary tract is discussed in contemporary scientific literature under the name of urogenital atrophy (UGA) or vulvovaginal atrophy (VVA) [1]. In 2014, a team of experts from two scientific associations – The North American Menopause Society (NAMS) and The International Society for the Study of Women’s Sexual Health (ISSWSH) – proposed a new terminology for postmenopausal atrophic symptoms, replacing the terms VVA and UGA with the term genitourinary syndrome of menopause (GSM) [2]. The change was motivated by the belief that this set of symptoms requires a more holistic therapeutic approach falling outside the scope of interest of gynaecologists and urologists only. The signs and symptoms of GSM are summarised in the Table 1. Table 1 Genitourinary syndrome of menopause (GSM) –symptoms and signs
Vitis species, vintage, and alcoholic fermentation do not drive population structure in Starmerella bacillaris (synonym Candida zemplinina) species

The yeast species Starmerella bacillaris (synonym Candida zemplinina) is widely associated with oenological ecosystems and is frequently isolated from grape and grape must. Previous work showed that the genetic diversity of this species is high in wine environments and it is shaped by geographic location. Most analysed C. zemplinina strains, however, have been isolated from Vitis vinifera, disregarding the existence of other worldwide‐distributed Vitis species used in winemaking. In this work, we address the impact of the Vitis species and geographic location on the genetic diversity of C. zemplinina. Microsatellite genotyping analysis was applied to two remarkable populations of C. zemplinina from Argentina and Portugal (Azores Archipelago), isolated from neighbouring V. vinifera and Vitis labrusca vineyards. The study also included a large population of previously characterized worldwide‐isolated C. zemplinina strains. Genetic analyses confirmed that geographic localization significantly shaped the genetic diversity of C. zemplinina. No genetic differentiation on the basis of the Vitis species was recorded, indicating that C. zemplinina populations from neighbouring V. vinifera and V. labrusca vineyards are genetically homogeneous. In addition, no impact of the vintage was found on the C. zemplinina populations being both highly diversified and homogeneous during initial stages of alcoholic fermentation. Altogether, these results confirmed that winemaking‐related factors (i.e., vintage, Vitis species, and alcoholic fermentation) do not impact the genetic diversity of C. zemplinina and that only geographic localization significantly shapes this yeast species.
A Comprehensive Analysis of 2D&3D Video Watching of EEG Signals by Increasing PLSR and SVM Classification Results

Despite the development of two- and three-dimensional (2D&3D) technology, it has attracted the attention of researchers in recent years. This research is done to reveal the detailed effects of 2D in comparison with 3D technology on the human brain waves. The impact of 2D&3D video watching using electroencephalography (EEG) brain signals is studied. A group of eight healthy volunteers with the average age of 31 ± 3.06 years old participated in this three-stage test. EEG signal recording consisted of three stages: After a bit of relaxation (a), a 2D video was displayed (b), the recording of the signal continued for a short period of time as rest (c), and finally the trial ended. Exactly the same steps were repeated for the 3D video. Power spectrum density (PSD) based on short time Fourier transform (STFT) was used to analyze the brain signals of 2D&3D video viewers. After testing all the EEG frequency bands, delta and theta were extracted as the features. Partial least squares regression (PLSR) and Support vector machine (SVM) classification algorithms were considered in order to classify EEG signals obtained as the result of 2D&3D video watching. Successful classification results were obtained by selecting the correct combinations of effective channels representing the brain regions.
Neoadjuvant Chemoradiotherapy and Liver Transplantation for Unresectable Hilar Cholangiocarcinoma: The Irish Experience of the Mayo Protocol

Background. Pioneered by the Mayo Clinic, multimodal therapy with neoadjuvant chemoradiotherapy and orthotopic liver transplant has emerged as a promising option for unresectable hilar cholangiocarcinoma (hCCA). This study reports the experience of the Irish National Liver Transplant Programme with the Mayo Protocol. Methods. All patients diagnosed with unresectable hCCA between 2004 and 2016, who were eligible for the treatment protocol, were prospectively studied. Results. Thirty-seven patients commenced chemoradiotherapy. Of those, 11 were excluded due to disease progression and 26 proceeded to liver transplantation. There were 24 males, the median age was 49, and 88% had underlying primary sclerosing cholangitis. R0 and pathologic complete response rates were 96% and 62%, respectively. Overall median survival was 53 months and 1-, 3-, and 5-year survival was 81%, 69%, and 55%, respectively. The median survival of patients achieving a pathologic complete response was 83.8 months compared with 20.9 months in the group with residual disease (P = 0.036). Six patients (23%) developed disease recurrence. Among the patients who developed metastatic disease during neoadjuvant treatment, median survival was 10.5 months compared with 53 months in patients who proceeded to transplant (P < 0.001). Conclusions. Neoadjuvant chemoradiotherapy followed by liver transplantation substantially increases the survival of patients with unresectable hCCA. Achieving a pathologic complete response confers a significant survival benefit.
Educating Students About Opioid Use Disorder and Treatments in the Community Using an Educational Video

Supplemental digital content is available in the text. Background A treatment gap exists for people in the community with opioid use disorders (OUDs). Stigma and lack of knowledge of how to access community resources contribute to this gap. One valuable resource that may help fill this gap is nursing students. Purpose This study examined the impact of an educational video on prelicensure and postlicensure nursing students' knowledge and attitudes toward people with OUD. Methods A pre-post study design was used to examine whether 406 nursing students' knowledge and attitudes changed after viewing an educational video. Knowledge and attitudes were measured by an online survey, consisting of demographics, an 8-item Knowledge and Attitudes survey, and the Drug and Drug Problems Perceptions Questionnaire. Results The educational video produced a statistically significant positive improvement on nursing students' knowledge and attitudes. Conclusion Educating nursing students about OUD and treatment options can help reduce stigma and improve care toward people with OUD.