bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effectiveness and Safety of Anti-CD19 Chimeric Antigen Receptor-T Cell Immunotherapy in Patients With Relapsed/Refractory Large B-Cell Lymphoma: A Systematic Review and Meta-Analysis
Authors: Ying Zhitao , Song Yuqin , Zhu Jun 
Published: April 2022

Aim:To investigate the effectiveness and safety of using chimeric antigen receptor (CAR) T cell therapies targeting CD19 in patients with diffuse large B-cell lymphoma (DLBCL).Methods:PubMed, Embase, and the Cochrane Library were searched for reports published from database inception up to July 2021. The present meta-analysis included clinical response outcomes, survival outcomes, and safety analyses. For qualitative analysis that could not be combined, the data were presented in a tabular form. Subgroup analyses were also performed according to the costimulatory domains, generic names, and study designs.Results:Twenty-seven studies (1,687 patients) were included. The pooled 12-months overall survival (OS) rate was 63% (95%CI: 56–70%). The pooled best overall response (BOR) was 74.0% (95%CI: 67–79%), with a best complete response (BCR) of 48% (95%CI: 42–54%) and a 3-months CR rate (CRR) of 41% (95%CI: 35–47%). The subgroup analyses by costimulatory domain suggested statistically significant differences in BOR and BCR, whereas not in the 12-months OS rate and 3-months CRR. Among the patients evaluable for safety, 78% (95%CI: 68–87%), 6% (95%CI: 3–10%), 41% (95%CI: 31–52%), and 16% (95%CI: 10–24%) experienced cytokine release syndrome (CRS), severe CRS, neurotoxicity, and severe neurotoxicity, respectively. Compared with the CD28 costimulatory domain, the 4-1BB-based products showed a better safety profile on any-grade CRS (p&lt; 0.01), severe CRS (p= 0.04), any-grade neurotoxicity (p&lt; 0.01), and severe neurotoxicity (p&lt; 0.01).Conclusion:Anti-CD19 CAR-T cell immunotherapy has promising effectiveness and tolerable severe AE profile in DLBCL patients. 4-1BB-based CAR-T cells have a similar 12-months OS rate and 3-months CRR with CD28-based products but a better safety profile. The costimulatory domain might not affect the survival outcomes.
Pregnancy and Neonatal Outcomes After Exposure to Alprazolam in Pregnancy
Authors: Lee Hyunji , Koh Jae-Whoan , Kim Young-Ah , Chun Kyoung-Chul , Han Jung Yeol , Hwang Jong Hee , Choi June-Seek , Joo Sung Hong , Kwon Hye-Young 
Published: April 2022

Alprazolam is a commonly prescribed benzodiazepine for anxiety or panic disorder, even in pregnant women. Information on the safety of alprazolam during pregnancy is insufficient. We aimed to evaluate pregnancy and neonatal outcomes after exposure to alprazolam during pregnancy. A prospective study was conducted on 725 pregnancies from January 2000 to December 2019. Participants were recruited through the Korean Mother-Safe Program, a service providing information on drug-induced teratogenic risk during pregnancy and breastfeeding. Exposed (N = 96) and non-exposed (N = 629) women to alprazolam during pregnancy were selected and followed-up until delivery. Pregnancy outcomes, including spontaneous abortion, still birth, low birth weight (LBW), preterm birth, Apgar score (at 1 and 5 min), and malformations were measured and compared. Multivariable logistic regression was performed to examine the association between alprazolam exposure and outcomes. The mean age was 32.9 (SD 4.0) years in the alprazolam-exposed group and 31.8 (SD 3.8) years in the unexposed group (p = 0.008). The alprazolam exposure group demonstrated a significantly higher likelihood of pregnancy and neonatal outcomes: spontaneous abortion (OR = 2.38; 95% CI 1.20–4.69), LBW (OR = 3.65; 95% CI 1.22–11.00), and Apgar score at 1 min ≤ 7 (OR = 2.19; 95% CI 1.02–4.67). There was no significant difference in congenital abnormalities between the exposure and non-exposure groups. Our findings confirmed that alprazolam exposure during pregnancy was significantly associated with adverse pregnancy and neonatal outcomes, including spontaneous abortion, low birth weight, and Apgar score at 1 min ≤ 7. Alprazolam during pregnancy should be appropriately regulated and monitored.
Minimal Physiologically-Based Pharmacokinetic (mPBPK) Metamodeling of Target Engagement in Skin Informs Anti-IL17A Drug Development in Psoriasis
Authors: Ayyar Vivaswath S. , Lee Jong Bong , Wang Weirong , Pryor Meghan , Zhuang Yanli , Wilde Thomas , Vermeulen An 
Published: April 2022

The pharmacologic effect(s) of biotherapeutics directed against soluble targets are driven by the magnitude and duration of free target suppression at the tissue site(s) of action. Interleukin (IL)-17A is an inflammatory cytokine that plays a key role in the pathogenesis of psoriasis. In this work, clinical trial data from two monoclonal antibodies (mAbs) targeting IL-17A for treatment of psoriasis (secukinumab and ixekizumab) were analyzed simultaneously to quantitatively predict their target engagement (TE) profiles in psoriatic skin. First, a model-based meta-analysis (MBMA) for clinical responses was conducted separately for each drug based on dose. Next, a minimal physiologically-based pharmacokinetic (mPBPK) model was built to assess skin site IL-17A target engagement for ixekizumab and secukinumab simultaneously. The mPBPK model captured the observed drug PK, serum total IL-17A, and skin drug concentration-time profiles reasonably well across the different dosage regimens investigated. The developed mPBPK model was then used to predict the average TE (i.e., free IL-17A suppression) in skin achieved over a 12-weeks treatment period for each drug following their respective regimens and subsequently assess the TE-efficacy response relationship. It was predicted that secukinumab achieved 98.6% average TE in the skin at 300 mg q4w SC while ixekizumab achieved 99.9% average TE under 160 mg (loading) followed by 80 mg q2w SC. While direct quantification of free IL-17A levels at the site of action is technically challenging, integrated mPBPK-MBMA approaches offer quantitative predictions of free IL-17A levels at the site of action to facilitate future drug development via IL-17A suppression in psoriasis.
Development of the Korean Medicine Core Outcome Set for Stroke Sequelae: Herbal Medicine Treatment of Elderly Patients With Stroke Sequelae in Primary Clinics
Authors: Cha Jiyun , Kim Sungha , Kim Pyung-Wha , Lee Hesol , Ko Mi Mi , Jang Soobin , Lee Myeong Soo 
Published: April 2022

Objectives: We developed a Korean medicine core outcome set for stroke sequelae (COS-SS-KM) to evaluate the effectiveness and safety of herbal medicine (HM) for stroke sequelae, especially for elderly stroke patients in primary clinics.Methods: We identified previously reported outcomes from a literature review and defined the list of outcomes and effect modifiers for the core outcome set (COS) questionnaire. Three rounds of modified Delphi consensus exercises with experts were conducted online for suitability assessment, and one round of a modified Delphi consensus exercise with primary clinicians was conducted for feasibility assessment.Results: The review identified 17 outcomes and 16 effect modifiers; moreover, six outcomes and one effect modifier were suggested by the experts. The final COS comprised 8 outcomes and 12 effect modifiers for history taking, and experts listed 13 major symptoms of stroke sequelae for symptom assessment. The clinicians agreed on the feasibility of the COS.Conclusion: This COS will help primary care researchers assess the effectiveness of pharmacotherapy, including HM, for elderly patients with stroke sequelae. Future studies should focus on reflecting the opinions of all stakeholders.
Electron Streaming Effect Associated With the Elekta Unity Anterior Imaging Coil
Authors: Powers Marcus , Baines John 
Published: April 2022

The presence of the static field in magnetic resonance guided radiation therapy (MRgRT) systems, such as the Elekta Unity MR-Linac (MRL), influences charged particle motion due to the Lorentz force in and around patients. Consequently, for the Unity, changes to out-of-field dose (OFD) relative to conventional linacs occur due to the electron streaming effect (ESE) and spiraling contaminant electrons (SCE). This work investigates OFD associated with irradiation of the anterior MR imaging coil, which is in situ for all treatments on the Unity. Film measurements and Monaco simulations were performed to quantify the magnitude of OFD at the superior and inferior ends of the coil as a function of coil tilt relative to the beam direction. The dependence of OFD on field size and the relative electron density (RED) assigned to the coil and surrounding air are reported. The doses at both coil ends were clinically significant, with nearly 23.0% of the Dmax dose to water being recorded for the largest field (8.0 × 22.0 cm2) and 6.8% for the smallest field (3.0 × 3.0 cm2). Monaco simulations of OFD agreed with film within 5.0%, when appropriate calculation conditions were set. OFD decreases as coil tilt is reduced, and there is no evidence of ESE when the coil is horizontal. Clinically, the potential magnitude of cranio–caudal streaming dose from a tilted coil necessitates the use of appropriate shielding. A clinical case involving coil-induced ESE during treatment of a lesion in the right angle is presented. The planning-based investigation revealed that ESE doses associated with the coil and an immobilization vacuum bag can be clinically significant.
Robust Reconstruction of Electrocardiogram Using Photoplethysmography: A Subject-Based Model
Authors: Tang Qunfeng , Chen Zhencheng , Guo Yanke , Liang Yongbo , Ward Rabab , Menon Carlo , Elgendi Mohamed 
Published: April 2022

Electrocardiography and photoplethysmography are non-invasive techniques that measure signals from the cardiovascular system. While the cycles of the two measurements are highly correlated, the correlation between the waveforms has rarely been studied. Measuring the photoplethysmogram (PPG) is much easier and more convenient than the electrocardiogram (ECG). Recent research has shown that PPG can be used to reconstruct the ECG, indicating that practitioners can gain a deep understanding of the patients’ cardiovascular health using two physiological signals (PPG and ECG) while measuring only PPG. This study proposes a subject-based deep learning model that reconstructs an ECG using a PPG and is based on the bidirectional long short-term memory model. Because the ECG waveform may vary from subject to subject, this model is subject-specific. The model was tested using 100 records from the MIMIC III database. Of these records, 50 had a circulatory disease. The results show that a long ECG signal could be effectively reconstructed from PPG, which is, to our knowledge, the first attempt in this field. A length of 228 s of ECG was constructed by the model, which was trained and validated using 60 s of PPG and ECG signals. To segment the data, a different approach that segments the data into short time segments of equal length (and that do not rely on beats and beat detection) was investigated. Segmenting the PPG and ECG time series data into equal segments of 1-min width gave the optimal results. This resulted in a high Pearson’s correlation coefficient between the reconstructed 228 s of ECG and referenced ECG of 0.818, while the root mean square error was only 0.083 mV, and the dynamic time warping distance was 2.12 mV per second on average.
Prevalence of Bullying Behaviors Among Students From a National University in the United Arab Emirates: A Cross-Sectional Study
Authors: Al-Darmaki Fatima , Al Sabbah Haleama , Haroun Dalia 
Published: April 2022

BackgroundThis study aims to investigate bullying behaviors among college students at one of the national universities in UAE, and also to examine the psychological characteristics of those who were exposed to, or have experienced bullying.MethodsA cross-sectional study was conducted on 839 undergraduate students at one of the national universities in the UAE. Students from all colleges participated in this study and were selected by using stratified random sampling. Participants completed a bullying survey designed for the study, in addition to three psychological measures [i.e., Aggression Questionnaire, Buss and Perry, 1992; The Primary Care Anxiety and Depression, El-Rufaie et al., 1997; and the Post Traumatic Stress Disorder (PTSD) for Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition (PCL-5), Weathers et al., 2013].ResultsThe prevalence rate of students being exposed to or engaged in bullying was 26.3% (221 out of 839). Of those, 72 students (8.7%) reported being bullied, 29 (3.6%) reported bullying others, and 185 (22.8%) reported witnessing friends being bullied. The most common types of bullying reported were traditional bullying (e.g., face-to-face bullying, verbal, and physical). Cyberbullying was not very common. More females reported being bullied in comparison to males and most of the aggressors were peer students. Overall, moderate level of aggressive personality traits and low levels of symptoms of depression, anxiety, and PTSD were reported for the total sample. T-tests revealed significant differences in the three psychological measures between those who did not experience bullying and those who did. The mean scores on the Aggression Questionnaire for those who bullied others were significantly higher than those who did not experience bullying.ConclusionExperiences of bullying seem to impact college students’ mental health in the UAE. Therefore, efforts need to focus on developing preventive programs to increase students’ awareness of bullying and its negative impact on campus environment. Offering psychological help for those who were exposed to bullying would help them to deal effectively with this trauma.
Health Literacy and Personality Traits in Two Types of Family Structure—A Cross-Sectional Study in China
Authors: Mai Jianrong , Yibo Wu , Ling Zhou , Lina Lin , Xinying Sun 
Published: April 2022

ObjectiveThe level of health literacy is one of the important factors affecting health outcomes. Family is an important place to shape personality traits, and people with different personalities will adopt different lifestyles, which will lead to variations in health outcomes. Therefore, this article aims to explore the relationship between health literacy and personality and its influencing factors in different family structures.MethodsThis was a cross-sectional study with 1,406 individuals. A questionnaire was utilized to measure health literacy, personality and demographic variables, including family structure. Canonical correlation analysis (CCA) and hierarchical multiple regression analysis were used to examine the relation between health literacy and personality traits between two types of family structure.ResultsCCA showed that the canonical correlation coefficients were 0.309 (p&lt; 0.001) and 0.347 (p&lt; 0.001), in two-parent family and single-parent family, respectively. The openness of personality traits exhibited the highest correlation with health literacy. Compared with the remaining personality traits, openness yielded the strongest effect (β = 0.485 and β = 0.830) in two types of family structure, respectively. Education and monthly income were significantly associated with health literacy.ConclusionOur results support the relation between health literacy and personality traits in two types of family structure.
The Effectiveness of Eye Movement Desensitization for Post-traumatic Stress Disorder in Indonesia: A Randomized Controlled Trial
Authors: Susanty Eka , Sijbrandij Marit , Srisayekti Wilis , Suparman Yusep , Huizink Anja C. 
Published: April 2022

ObjectivePost-traumatic stress disorder (PTSD) may affect individuals exposed to adversity. Eye Movement Desensitization and Reprocessing (EMDR) is an evidence-based trauma-focused psychotherapy for PTSD. There is still some debate whether the eye movements (EMs) are an effective component of EMDR. The primary aim of this study was to investigate the effectiveness of Eye Movement Desensitization (EMD) treatment in reducing PTSD symptoms compared to a retrieval-only active control condition. We also investigated whether PTSD symptom reduction was associated with reductions in depression and anxiety, and improvements in quality of life.MethodologyAdult PTSD patients (n= 91) were recruited at public psychological services in Jakarta, Bandung and Cimahi, Indonesia. PTSD was diagnosed with the Structured Clinical Interview for DSM-5 disorders (SCID-5). Participants were randomized into: EMD (n= 47) or retrieval-only (n= 44). EMD consisted of clinical history and treatment planning, preparation, assessment, EMs, closure, whereas retrieval-only consisted of the same elements except EMs. Data were collected at baseline (T0), 1-week post-treatment (T1), 1-month follow-up (T2), and 3-months follow-up (T3). Outcome measures included the PTSD Checklist for DSM-5 (PCL-5), Hopkins Symptoms Checklist-25 (HSCL-25), and the World Health Organization Quality of Life–BREF (WHOQoL–BREF). Data were analyzed with linear mixed model analysis in R Statistics.ResultsAlthough there were main effects of time indicating reductions for both EMD and retrieval-only in PCL-5 and HSCL-25 scores, and improvements in WHOQoL-BREF scores at T1, T2, and T3, no significant differences in PCL-5, HSCL-25, and WHOQoL-BREF total scores between the EMD and retrieval-only groups at T1, T2, and T3 were found (all group x time interactionp’s &gt; 0.005).ConclusionWithin a clinical sample of PTSD patients in Indonesia, both EMD and retrieval-only was associated with reductions in symptoms of PTSD, anxiety and depression, and improvements in quality of life, although EMs did not add to the efficacy of the treatments. Further research to examine the underlying mechanisms of EMDR’s effective treatment elements in clinical samples is needed.Clinical Trial Registration[www.ClinicalTrials.gov], identifier [ISRCTN55239132].
Prediction of Disorientation by Accelerometric and Gait Features in Young and Older Adults Navigating in a Virtually Enriched Environment
Authors: Teipel Stefan J. , Amaefule Chimezie O. , Lüdtke Stefan , Görß Doreen , Faraza Sofia , Bruhn Sven , Kirste Thomas 
Published: April 2022

ObjectiveTo determine whether gait and accelerometric features can predict disorientation events in young and older adults.MethodsCognitively healthy younger (18–40 years, n = 25) and older (60–85 years, n = 28) participants navigated on a treadmill through a virtual representation of the city of Rostock featured within the Gait Real-Time Analysis Interactive Lab (GRAIL) system. We conducted Bayesian Poisson regression to determine the association of navigation performance with domain-specific cognitive functions. We determined associations of gait and accelerometric features with disorientation events in real-time data using Bayesian generalized mixed effect models. The accuracy of gait and accelerometric features to predict disorientation events was determined using cross-validated support vector machines (SVM) and Hidden Markov models (HMM).ResultsBayesian analysis revealed strong evidence for the effect of gait and accelerometric features on disorientation. The evidence supported a relationship between executive functions but not visuospatial abilities and perspective taking with navigation performance. Despite these effects, the cross-validated percentage of correctly assigned instances of disorientation was only 72% in the SVM and 63% in the HMM analysis using gait and accelerometric features as predictors.ConclusionDisorientation is reflected in spatiotemporal gait features and the accelerometric signal as a potentially more easily accessible surrogate for gait features. At the same time, such measurements probably need to be enriched with other parameters to be sufficiently accurate for individual prediction of disorientation events.
Attitude of Nutrition Experts Toward Psychotherapy and Virtual Reality as Part of Obesity Treatment—An Online Survey
Authors: Gemesi Kathrin , Holzmann Sophie Laura , Hochrein Regine , Döllinger Nina , Wienrich Carolin , Weinberger Natascha-Alexandra , Luck-Sikorski Claudia , Holzapfel Christina 
Published: April 2022

BackgroundThe management of obesity requires lifestyle-based interventions covering nutrition, physical activity, and behavior. As part of cognitive behavioral therapy (CBT), body image therapy approaches can be used not only by psychotherapists. One tool to conduct behavioral therapy is virtual reality (VR). It is unknown, whether nutrition experts conduct behavioral therapy, and whether they would like to use VR technology as a tool to conduct body image therapy as part of obesity management.ObjectiveThis survey aimed to collect data from nutrition experts treating people with obesity about the status quo regarding behavioral and body image therapy as part of obesity management, and regarding their attitude toward VR in obesity therapy.MethodsThe survey was conducted online in autumn 2020. Participants were recruited digitally through expert and professional associations. The standardized questionnaire included items concerning sociodemographic, professional status, behavioral therapy, body image, and VR. The descriptive analysis was performed with Excel, the subgroup analyses with R.ResultsData from 158 nutrition experts was analyzed. Participants were mostly female (98/102, 96.1%) and had a mean age of 45.6 ± 11.3 years (n = 101). Most of the survey participants (93/124, 75.0%) stated to use behavioral treatment methods in case of weight reduction as the primary target. More than half of the participants stated to address body image (99/150, 66.0%). Almost all (111/112, 99.1%) nutrition experts have never used VR-glasses. The suitability and importance of VR technology as part of obesity therapy was estimated as neutral by around 50%. Overall, no statistically significant difference could be shown between age groups regarding attitudes toward VR in obesity treatment.ConclusionThe results of this non-representative survey indicate that nutrition experts do not use VR technology in nutrition counseling sessions to treat obesity. In addition, survey participants have a positive attitude to VR technology, whereas they are not familiar with this technology. In future, VR technology might support nutrition experts of every age using elements of body image therapy.Survey RegistrationThe German Register of Clinical Studies (Registration Number: DRKS00022853).