Miracle-dz/UniFAR-FTUs huggingface dataset:
Development and Utility of an ELISA Method for Sensitive and Specific Detection of IgE Antidrug Antibodies

Biologics can potentially induce unwanted immune responses, leading to formation of antidrug antibodies (ADA) of various affinity, isotypes, and subclasses. Among them, antigen and drug-specific immunoglobulin E (IgE) antibodies have been reported to have potential correlation with hypersensitivity and anaphylaxis in particular. Recent regulatory guidance on immunogenicity testing has recommended the measurement of antigen-specific IgE antibodies for biologics with a reported high risk of anaphylaxis using assays with sensitivities in the high pg/mL to low ng/mL range. Nevertheless, IgE ADA remains challenging to detect due to their being the least abundant isotype in blood serum samples and the potential for interference in the bioanalytical methods due to high levels of endogenous immunoglobulin G (IgG) and immunoglobulin M (IgM) ADA, not to mention the nonspecific total serum IgE antibodies. Another challenge in developing IgE ADA assays is the need to create a surrogate drug-specific IgE antibody positive control to monitor the performance of the assay for the intended use. In this case study, utilizing a human IgE antidrug antibody positive control and a human IgE receptor as capture, an enzyme-linked immunosorbent assay (ELISA) method was developed for the measurement of IgE ADA, meeting the regulatory expectations, with excellent assay sensitivity, selectivity, specificity, and tolerance towards potential interference in serum samples. This assay format could be readily adapted and implemented to assess drug-specific IgE antibodies in the event of drug-related anaphylaxis in clinical and in nonclinical development programs.
Implementing cognitive behavioral therapy-enhanced in a routine inpatient and outpatient setting: Comparing effectiveness and treatment costs in two consecutive cohorts.

BACKGROUND Even though evidence-based interventions can enhance clinical outcomes and cost effectiveness, in the field of eating disorders, implementation of empirically supported treatments (ESTs) in routine inpatient and outpatient settings is slow. OBJECTIVE This study examined differential (cost-) effectiveness, after implementing evidence-based cognitive behavioral therapy-enhanced (CBT-E) throughout a Dutch treatment center. METHOD Two consecutive cohorts of adult patients, BMI between 17.5 and 40, were compared, with one cohort (N = 239) receiving treatment-as-usual (TAU) between 2012 and 2014 and the other (N = 320) receiving CBT-E between 2015 and 2017. RESULTS Eating disorder pathology, measured with self-reports, decreased significantly in both cohorts; overall, no differences in clinical outcomes between both cohorts were found. Treatment costs and treatment duration were considerably lower in 2015-2017. When limiting the cost analysis to direct costs, there is a 71% likelihood that CBT-E is more cost-effective and a 29% likelihood that CBT-E leads to fewer remissions at lower costs, based on the distribution of the cost-effectiveness plane. The likelihood that TAU leads to lower costs is 0%. DISCUSSION Findings show that implementing an EST throughout inpatient and outpatient settings leads to lower costs with similar treatment effect and has the advantage of shorter treatment duration and a shorter inpatient stay.
The Interchromatin Compartment Participates in the Structural and Functional Organization of the Cell Nucleus

This article focuses on the role of the interchromatin compartment (IC) in shaping nuclear landscapes. The IC is connected with nuclear pore complexes (NPCs) and harbors splicing speckles and nuclear bodies. It is postulated that the IC provides routes for imported transcription factors to target sites, for export routes of mRNA as ribonucleoproteins toward NPCs, as well as for the intranuclear passage of regulatory RNAs from sites of transcription to remote functional sites (IC hypothesis). IC channels are lined by less‐compacted euchromatin, called the perichromatin region (PR). The PR and IC together form the active nuclear compartment (ANC). The ANC is co‐aligned with the inactive nuclear compartment (INC), comprising more compacted heterochromatin. It is postulated that the INC is accessible for individual transcription factors, but inaccessible for larger macromolecular aggregates (limited accessibility hypothesis). This functional nuclear organization depends on still unexplored movements of genes and regulatory sequences between the two compartments.
A word or two about nonwords: Frequency, semantic neighborhood density, and orthography-to-semantics consistency effects for nonwords in the lexical decision task.

For the most part, the effects of lexical-distributional properties of words on visual word recognition are well-established. More uncertainty remains, however, about the influence of these properties on lexical processing for nonwords. The work presented here investigates the mechanisms that guide nonword processing through an analysis of lexical decision latencies for 18,547 words and 27,079 nonwords in the British Lexicon Project (Keuleers, Lacey, Rastle, & Brysbaert, 2012) using piecewise generalized mixed models (pamms; Bender, Groll, & Scheipl, 2018; Bender & Scheipl, 2018; Bender, Scheipl, Hartl, Day, & Küchenhoff, 2018). The pamm analysis of the data revealed 2 novel effects for nonwords in the lexical-decision task. First, whereas previous studies reported effects of base word frequency, the current study is the first to document a true nonword frequency effect. Second, we report effects of semantic neighborhood density and orthography-to-semantics consistency; not only for words, but also for nonwords. The effects of frequency, semantic neighborhood density and orthography-to-semantics consistency are facilitatory for words, but inhibitory for nonwords. The pamm analysis offers insights into the temporal development of the effects of lexical-distributional variables that are not available through more traditional analysis techniques and that shed new light on lexical processing in visual word recognition tasks. The implications of the reported results for models of visual word recognition are discussed. (PsycINFO Database Record (c) 2020 APA, all rights reserved).
A critical review of current evidence on multiple types of discrimination and mental health.

Little is known about people who experience multiple types of discrimination (e.g., racism and heterosexism). While some work suggests that multiply discriminated groups are at higher risk for poor mental health, other studies propose that they may develop resilience against additional kinds of discrimination. We conducted a review of published studies on the relationship between multiple types of discrimination and mental health to critically examine evidence in support of broad risk and resilience models. Using PRISMA guidelines, we identified 40 studies that met our inclusion criteria. Typically, studies examined either whether experiencing multiple discrimination was related to poorer mental health, or whether one kind of discrimination was more predictive of poor mental health. Studies generally showed support for the risk model, with multiple forms of discrimination associated with higher risk for depression symptoms. Furthermore, both racism and heterosexism uniquely predicted symptoms of depression, although initial evidence suggested that only heterosexism predicted suicidality among lesbian, gay, bisexual, transgender, and queer (LGBTQ) racial/ethnic minorities. Findings on multiple discrimination and other mental health problems (e.g., anxiety, posttraumatic stress disorder [PTSD], distress, and substance use) were mixed. The current evidence suggests that multiply discriminated groups exhibit higher risk for some mental health problems, particularly depression symptoms. However, methodological problems abound in this literature (e.g., correspondence between study sample and types of discrimination assessed), which limits our ability to draw clear conclusions about multiple discrimination. We propose that to further our understanding of how multiple kinds of discrimination may affect mental health, studies must remedy these and other issues. (PsycINFO Database Record (c) 2020 APA, all rights reserved).
Dopaminergic neurons can influence heat-box place learning in Drosophila

Abstract Dopamine provides crucial neuromodulatory functions in several insect and rodent learning and memory paradigms. However, an early study suggested that dopamine may be dispensable for aversive place memory in Drosophila. Here we tested the involvement of particular dopaminergic neurons in place learning and memory. We used the thermogenetic tool Gr28bD to activate protocerebral anterior medial (PAM) cluster and non-PAM dopaminergic neurons in an operant way in heat-box place learning. We show that activation of PAM neurons influences performance during place learning, but not during memory testing. These findings provide a gateway to explore how dopamine influences place learning.
Review of Pediatric Otolaryngology Clinical Trials: Past Trends and Future Opportunities

Pediatric otolaryngologic conditions are highly prevalent in the United States. Although data gathered from clinical trials drive therapeutic strategies, the trends of research in pediatric otolaryngology remain unclear. The objective of this study was to characterize recent trials in pediatric otolaryngology to better understand current directions of study and to identify opportunities for future research.
Unplanned Out-of-Hospital Birth—Short and Long-Term Consequences for the Offspring

The unpredictable nature of childbirth infrequently results in unplanned out-of-hospital birth, in a pre-hospital setting. We evaluated the perinatal and long-term outcome of children accidentally born out-of-hospital. This was a population-based analysis of singleton deliveries occurring at a single tertiary hospital. The maternal characteristics and pregnancy outcome of unplanned out-of-hospital births were compared with in-hospital attended deliveries. Long-term cumulative incidence of hospitalizations (up to 18 years) involving respiratory, neurological, endocrine or infectious morbidity were evaluated using Kaplan–Meier survival curves and Cox regression models were used to control for confounders. In total, 243,682 deliveries were included, and 1.5% (n = 3580) were unplanned out-of-hospital births. Most occurred in multiparous women, and about a quarter of these women had inadequate prenatal care. Perinatal mortality rate was significantly higher for out-of-hospital births as compared with in-hospital births (OR = 2.9; 95% CI 2.2–3.8, p < 0.001). Kaplan–Meier survival curves demonstrated a significantly lower cumulative incidence of hospitalizations of children born out-of-hospital and the Cox models showed that hospitalization rates involving any of the above morbidities were significantly lower in children born out-of-hospital. While perinatal mortality was higher in unplanned out-of-hospital births, offspring born out-of-hospital showed a lower incidence of hospitalizations involving a variety of morbidities, possibly owing to under-utilization of healthcare services in this population.
Microscopic Observation Drug Susceptibility (MODS) Assay: A Convenient Method for Determining Antibiogram of Clinical Isolates of Mycobacterium tuberculosis in Ghana

(1) Background: Present methods for drug susceptibility tests (DST) rely on culture methods that are sophisticated and relatively faster, or a slow and cheaper option. These methods frustrate disease control; therefore, there is a need for methods that incorporate key functions of microscopy and culture, with reduced cost burden and sophistry. Thus, the purpose of this study was to identify which, among the most commonly used (in Ghana) methods, can conveniently be used at health centers located in rural areas for effective DST determination of Mycobacterium tuberculosis (MTB). (2) Methods: Mycobacterium tuberculosis isolates were tested for their susceptibility to streptomycin, isoniazid, rifampicin, ethambutol (SIRE), and pyrazinamide by microscopic observation drug susceptibility (MODS) and BACTEC MGIT 960 methods. Evaluations were based on shorter turnaround periods, rapidity, ease of use, cost, etc. A comparative analysis was statistically expressed as kappa values. (3) Results: Endpoints for drug susceptibilities by MODS averaged 13 days (7–32), whilst that for BACTEC MGIT 960 was 10 days with a further 12 days to detect resistance. Therefore, a turnaround period of 22 days was needed for DST by BACTEC MGIT 960, compared to 13 days for MODS. There were differences in correlation levels between the two methods, as determined by their kappa values. (4) Conclusion: The MODS assay was found to be less costly, more user-friendly, and still able to be conveniently used at health centers located in rural areas known to be endemic for TB, particularly in Ghana.
Response to the letter to the editor regarding: Titrate to equilibrate and not exsanguinate! Characterization and validation of a novel partial resuscitative endovascular balloon occlusion of the aorta catheter in normal and hemorrhagic shock conditions.

REFERENCES 1. Forte D, Do WS, Weiss JB, Sheldon RR, Kuckelman JP, Eckert MJ, Martin MJ. Titrate to equilibrate and not exsanguinate! : characterization and validation of a novel partial resuscitative endovascular balloon occlusion of the aorta catheter in normal and hemorrhagic shock conditions. J Trauma Acute Care Surg. 2019;87(5): 1015–1025. 2. Johnson MA, Davidson AJ, Russo RM, Ferencz SA, Gotlib O, Rasmussen TE, Neff LP, Williams TK. Small changes, Big Effects: The hemodynamics of partial and complete aortic occlusion to inform next generation resuscitation techniques and technologies. J Trauma Acute Care Surgery. 2017;82(6):1106–1111. 3. Beyer CA, Hoareau GL, Tibbits EM, Davidson AJ, DeSoucy ED, Simon MA, Grayson JK, Neff LP, Williams TK, Johnson MA. Resuscitative endovascular balloon occlusion of the aorta induced myocardial injury is mitigated by endovascular variable aortic control. J Trauma Acute Care Surg. 2019; 87(3):590–598. 4. Williams TK, Tibbits EM, Hoareau GL, Simon MA, Davidson AJ, DeSoucy ES, Faulconer ER, Grayson JK, Neff LP, Johnson MA. Endovascular variable aortic control (EVAC) versus resuscitative endovascular balloon occlusion of the aorta (REBOA) in a swine model of hemorrhage and ischemia reperfusion injury. J Trauma Acute Care Surg. 2018; 85(3):519–526. 5. Williams TK, Neff LP, Tibbits EM, Hoareau GL, Simon MA, Davidson AJ, DeSoucy ES, Robert Faulconer R, Grayson JK, Johnson MA. A novel automated endovascular variable aortic control
Prolapse Recurrence After Sacrocolpopexy Mesh Removal: A Retrospective Cohort Study.

OBJECTIVES There is limited literature regarding outcomes after sacrocolpopexy mesh removal. We sought to compare the proportion of prolapse recurrence in women after sacrocolpopexy mesh removal with women who underwent sacrocolpopexy without subsequent mesh removal. We hypothesize that more women will experience prolapse recurrence after mesh removal. METHODS This is a retrospective cohort study of women who underwent sacrocolpopexy mesh removal between 2010 and 2019. These patients were time matched with women who had a sacrocolpopexy but did not undergo mesh removal. Prolapse recurrence was defined as the leading edge past the hymen or retreatment. Analysis was done using χ, Wilcoxon rank-sum, or t test with a Cox proportional hazard model to assess the association between mesh removal and time to recurrence. RESULTS We identified 26 mesh removals, which were matched with 78 patients without mesh removal. The most common indications for mesh removal were exposure (69.2%) and pain (57.7%). Women who underwent mesh removal were more likely to have Mersilene mesh (19.2% vs 1.3%, P = 0.006). Recurrence occurred in 46% of women who had mesh removal compared with 7.7% in those without (P < 0.001). When adjusted for age, parity, menopause, smoking, and diabetes status, those who had mesh removal had a 15 times higher hazard of prolapse recurrence (adjusted hazard ratio = 15.4, 95% confidence interval = 4.3-54.8, P = <.0001). CONCLUSIONS When compared with time-matched controls, women who underwent sacrocolpopexy mesh removal had a significantly higher proportion of prolapse recurrence. Prospective studies are needed to further explore the utility of concomitant prolapse repair at the time of mesh removal.
Ultra-Short-Term and Short-Term Heart Rate Variability Recording during Training Camps and an International Tournament in U-20 National Futsal Players

The aim of this study was to examine ultra-short-term and short-term heart rate variability (HRV) in under-20 (U-20) national futsal players during pre-tournament training camps and an official tournament. Fourteen male U-20 national futsal players (age = 18.07 ± 0.73 yrs; height = 169.57 ± 8.40 cm; body weight = 64.51 ± 12.19 kg; body fat = 12.42% ± 3.18%) were recruited to participate in this study. Early morning 10 min resting HRV, Borg CR-10 scale session rating of perceived exertion (sRPE), and general wellness questionnaire were used to evaluate autonomic function, training load, and recovery status, respectively. Log-transformed root mean square of successive normal-to-normal interval differences (LnRMSSD) was used to compare the first 30 s, first 1 min, first 2 min, first 3 min, and first 4 min with standard 5 min LnRMSSD. Mean (LnRMSSDmean) and coefficient of variation (LnRMSSDcv) of LnRMSSD were used to compare the different time segments of HRV analysis. The result of LnRMSSDmean showed nearly perfect reliability and relatively small bias in all comparisons. In contrast, LnRMSSDcv showed nearly perfect reliability and relatively small bias from 2-4 min time segments in all study periods. In conclusion, for accuracy of HRV measures, 30 s or 1 min ultra-short-term record of LnRMSSDmean and short-term record of LnRMSSDcv of at least 2 min during the training camps are recommended in U-20 national futsal players.
Improved Child Mental Health Following Brief Relationship Enhancement and Co-Parenting Interventions During the Transition to Parenthood

The transition to parenthood has been identified as a significant relationship stressor. Many couples report declines in relationship satisfaction and difficulty with individual stress and co-parenting—problems that have been associated with both child temperament as well as emotional and behavioral problems. Several parenting and relationship interventions have been developed to buffer against these difficulties. In the current study, we report secondary analyses of a randomized controlled trial of brief (6-h) interventions that focused on improving either relationship satisfaction or co-parenting, delivered during pregnancy and the early postpartum period. In this trial, 90 opposite-sex couples (180 participants), who were pregnant with their first child, and were assessed as being at high risk for declines in relationship satisfaction, were randomized to receive either (1) a relationship intervention, (2) a co-parenting intervention, or (3) an information control. At 12 months postpartum, couples who received either the relationship or co-parenting intervention rated their infants as having lower negative emotionality and as having fewer externalizing symptoms compared to the information-only control. Lower externalizing symptoms at 12 months were, in turn, associated with reduced externalizing symptoms at 24 months postpartum. Whereas, lower ratings of child negative emotionality at 12 months were associated with reduced internalizing symptoms at 24 months postpartum. These results indicate that brief relationship or co-parenting interventions delivered during the transition to parenthood have secondary benefits for child mental health.
Effect of Glycine on BV-2 Microglial Cells Treated with Interferon-γ and Lipopolysaccharide

Microglia are first-line defense antigen-presenting phagocytes in the central nervous system. Activated microglial cells release pro-inflammatory cytokines and can trigger an oxidative burst. The amino acid glycine exerts anti-inflammatory, immunomodulatory and cytoprotective effects and influences cell volume regulation. This study aimed to investigate the role of glycine in the modulation of inflammatory processes in mouse BV-2 microglial cells. Inflammatory stress was induced by lipopolysaccharide/interferon-γ (LPS/IFN-γ) treatment for 24 h in the absence or presence of 1 or 5 mM glycine. Cells were analyzed by flow cytometry for cell volume, side scatter, apoptosis/necrosis and expression of activation-specific surface markers. Apoptosis progression was monitored by life cell imaging. Reduced glutathione/oxidized glutathione (GSH/GSSG) ratios and release of the pro-inflammatory cytokines IL-6 and TNF-α were measured using luminescence-based assays and ELISA, respectively. We found that LPS/IFN-γ-induced apoptosis was decreased and the fraction of living cells was increased by glycine. Expression of the surface markers CD11b, CD54 and CD80 was dose-dependently increased, while IL-6 and TNF-α release was not altered compared to LPS/IFN-γ-treated cells. We showed that in BV-2 microglial cells glycine improves viability and counteracts deleterious responses to LPS/IFN-γ, which might be relevant in neurodegenerative processes associated with inflammation, like Alzheimer’s or Parkinson’s disease.
Nursing stress factors affecting turnover intention among hospital nurses.

AIMS This study aimed to identify the nursing stress factors, which affect turnover intention in hospital nurses. BACKGROUND Nursing stress is known to be an important predictor of turnover intention in nurses. Although nurses experience various sources of stress across work environments, cultures, and generations, little is known about the stress factors affecting turnover intention in nurses. DESIGN A descriptive cross-sectional design was employed. METHODS A total of 329 nurses were recruited through convenience sampling from 27 hospitals in South Korea. Data were collected from May to November 2018 using a questionnaire. RESULTS Among the stress factors, stress from patients and their families, workload stress, stress from conflicts with supervisors, and stress from conflicts with peers were associated with turnover intention in hospital nurses. These variables explained 40.0% of the variance in turnover intention among hospital nurses. CONCLUSIONS Stress from interpersonal relationships with patients and their families, supervisors, and peers may have a considerable impact on turnover intention. To reduce nursing turnover intention, coping strategies to reduce stress from patients and their families should be established. It is necessary to provide programmes that foster interpersonal relationship skills in the workplace. Nurse managers may encourage communication among nurses to establish positive relationships.