bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genome sequences of human cytomegalovirus strain TB40/E variants propagated in fibroblasts and epithelial cells
Authors: Al Qaffas Ahmed , Camiolo Salvatore , Vo Mai , Aguiar Alexis , Ourahmane Amine , Sorono Myrna , Davison Andrew J. , McVoy Michael A. , Hertel Laura 
Published: June 2021

AbstractThe advent of whole genome sequencing has revealed that common laboratory strains of human cytomegalovirus (HCMV) have major genetic deficiencies resulting from serial passage in fibroblasts. In particular, tropism for epithelial and endothelial cells is lost due to mutations disrupting genes UL128, UL130, or UL131A, which encode subunits of a virion-associated pentameric complex (PC) important for viral entry into these cells but not for entry into fibroblasts. The endothelial cell-adapted strain TB40/E has a relatively intact genome and has emerged as a laboratory strain that closely resembles wild-type virus. However, several heterogeneous TB40/E stocks and cloned variants exist that display a range of sequence and tropism properties. Here, we report the use of PacBio sequencing to elucidate the genetic changes that occurred, both at the consensus level and within subpopulations, upon passaging a TB40/E stock on ARPE-19 epithelial cells. The long-read data also facilitated examination of the linkage between mutations. Consistent with inefficient ARPE-19 cell entry, at least 83% of viral genomes present before adaptation contained changes impacting PC subunits. In contrast, and consistent with the importance of the PC for entry into endothelial and epithelial cells, genomes after adaptation lacked these or additional mutations impacting PC subunits. The sequence data also revealed six single noncoding substitutions in the inverted repeat regions, single nonsynonymous substitutions in genes UL26, UL69, US28, and UL122, and a frameshift truncating gene UL141. Among the changes affecting protein-coding regions, only the one in UL122 was strongly selected. This change, resulting in a D390H substitution in the encoded protein IE2, has been previously implicated in rendering another viral protein, UL84, essential for viral replication in fibroblasts. This finding suggests that IE2, and perhaps its interactions with UL84, have important functions unique to HCMV replication in epithelial cells.
Treatment adherence in tyrosinemia type 1 patients
Authors: González-Lamuño Domingo , Sánchez-Pintos Paula , Andrade Fernando , Couce María L. , Aldámiz-Echevarría Luís 
Published: June 2021

Abstract
Background
While therapeutic advances have significantly improved the prognosis of patients with hereditary tyrosinemia type 1 (HT1), adherence to dietary and pharmacological treatments is essential for an optimal clinical outcome. Poor treatment adherence is well documented among patients with chronic diseases, but data from HT1 patients are scarce. This study evaluated pharmacological and dietary adherence in HT1 patients both directly, by quantifying blood levels nitisinone (NTBC) levels and metabolic biomarkers of HT1 [tyrosine (Tyr), phenylalanine (Phe), and succinylacetone]; and indirectly, by analyzing NTBC prescriptions from hospital pharmacies and via clinical interviews including the Haynes–Sackett (or self-compliance) test and the adapted Battle test of patient knowledge of the disease.

Results

This observational study analyzed data collected over 4 years from 69 HT1 patients (7 adults and 62 children; age range, 7 months–35 years) who were treated with NTBC and a low-Tyr, low-Phe diet. Adherence to both pharmacological and, in particular, dietary treatment was poor. Annual data showed that NTBC levels were lower than recommended in more than one third of patients, and that initial Tyr levels were high (> 400 µM) in 54.2–64.4% of patients and exceeded 750 µM in 25.8% of them. Remarkably, annual normalization of NTBC levels was observed in 29.4–57.9% of patients for whom serial NTBC determinations were performed. Poor adherence to dietary treatment was more refractory to positive reinforcement: 36.2% of patients in the group who underwent multiple analyses per year maintained high Tyr levels during the entire study period, and, when considering each of the years individually this percentage ranged from 75 to 100% of them. Indirect methods revealed percentages of non-adherent patients of 7.3 and 15.9% (adapted Battle and Haynes tests, respectively).

Conclusions
Despite initially poor adherence to pharmacological and especially dietary treatment among HT1 patients, positive reinforcement at medical consultations resulted in a marked improvement in NTBC levels, indicating the importance of systematic positive reinforcement at medical visits.
Prophylactic ankle supports effects on time to stabilization, perceived stability and ground reaction force during lateral landing in female collegiate athletes with chronic ankle instability
Authors: Yalfani Ali , Raeisi Zahra 
Published: June 2021

Abstract
Background
This study was designed to investigate effects of Kinesiotape (KT) with closed basket weave method and lace-up braces (LB) on the vertical time to stabilization, peak vertical ground reaction force (PvGRF), and time to PvGRF as well as perceived stability during lateral landing of participants with chronic ankle instability before and after fatigue.

Methods
Thirty female college athletes with chronic ankle instability of three conditions (control, KT, and LB) performed lateral landing from a 30 cm high step on the plantar pressure platform pre and post fatigue.

Results
The pre-test findings on the rearfoot, of LB indicated negatively increased the PvGRF force (F2,58=3.63, P = 0.04) and decreased the time to PvGRF (F2,58=4.67, P = 0.01). The Bonferroni post-hoc testing revealed LB condition increased the PvGRF than the control (P = 0.002) and KT (P = 0.038). Also, the post-hoc testing showed LB condition decreased the time to PvGRF force than the control (P = 0.05) and KT (P = 0.01). The LB negatively prolonged vertical time to stabilization in the forefoot (F2,58=6.74, P = 0.002) and rearfoot (F2,58=6.13, P = 0.004) after fatigue. The post-hoc testing revealed LB condition generated a slower vertical time to stabilization than the control and KT conditions (P ≤ 0.05). The use of KT had no positive effects as elevated the PvGRF in the forefoot post fatigue (F2,58=7.11, P = 0.002). The post-hoc test uncovered that KT augmented the PvGRF than control (P = 0.01) and LB (P < 0.001). On the other hand, using KT had psychological effects at pre-fatigue which resulting significantly greater in perceived stability compared to other conditions (F2,58=9.65, P < 0.001). The post-hoc test showed that using KT increased perceived stability than LB (P = 0.004) and control (P < 0.001). Moreover, perceived stability improved significantly in KT and LB compared to the control condition at the post-fatigue (P ≤ 0.001).

Conclusions
Despite the positive psychological impact of the prophylactic ankle supports, there were no positive effect on the vertical time to stabilization, PvGRF, and time to PvGRF. Further studies are needed to distinguish the psychological and actual effects of prophylactic ankle supports on athletes with chronic ankle instability.
How are emotional distress and reassurance expressed in medical consultations for people with long-term conditions who were unable to receive curative treatment? A pilot observational study with huntington’s disease and prostate cancer
Authors: Anderson Niall C. , Zhou Yuefang , Humphris Gerry 
Published: June 2021

Abstract
Objective
It is unclear whether how people with long-term conditions express distress, and how clinicians respond, influences perceptions of consultation outcomes. The pilot study examined emotional distress and reassurance in consultations with people whose long-term conditions (at the time of consultations) were treated using active surveillance or symptom management (as no curative treatment was suitable).

Methods
An observational pilot study was conducted involving consultations between people with long-term conditions and their respective clinician. Consultations between three clinicians (two Huntington’s Disease; one Prostate Cancer) and 22 people with long-term conditions (11 Huntington’s Disease; 11 Prostate Cancer) were audio-recorded. Participants also completed an expanded Consultation and Relational Empathy (CARE) Measure. Two researchers coded sessions using Verona Coding Definitions of Emotional Sequences (VR-CoDES/VR-CoDES-P). Code frequencies were calculated, t tests performed between conditions, and Pearson’s correlations performed for associations between CARE responses and clinician utterances.

Results
People with long-term conditions expressed emotional distress on average 4.45 times per session, averaging 1.09 Concern and 3.36 Cue utterances. Clinicians responded with more explicit (2.59) and space-providing (3.36), than non-explicit (1.86) and space-reducing (1.09), responses per session. Clinicians expressed spontaneous reassurance on average 5.18 times per session, averaging 3.77 Cognitive and 1.5 Affective reassurance utterances. Huntington’s Disease consultations featured significantly more 'Cues', 'Concerns' and 'Overall' 'Emotional Distress', and 'Cognitive' and 'Overall' ‘Reassurance'.

Conclusion
Emotional distress was expressed more using hints than explicit concern utterances. Clinicians predominantly explicitly explored distress rather than providing information/advice and provided advice using spontaneous cognitive reassurance. People with Huntington’s Disease expressed more concerns and received more reassurance, indicating different needs between conditions. Future research is required to explore emotional distress and reassurance in a larger sample of participants and long-term condition types, and how the practical implications of these findings may be used to enhance outcomes of consultations.

Trial registration
N/A.
Mindfulness-based stress reduction adapted to pregnant women with psychosocial vulnerabilities—a protocol for a randomized feasibility study in a Danish hospital-based outpatient setting
Authors: Skovbjerg S. , Birk D. , Bruggisser S. , Wolf A. L. A. , Fjorback L. 
Published: June 2021

Abstract
Background
This protocol is for a feasibility study of a mindfulness-based stress reduction (MBSR) program adapted for pregnant women with psychosocial vulnerabilities. The rationale for the study is the need for a wider array of evidence-based options to address prenatal mental health care needs in pregnant women. MBSR is a promising mental health intervention but has not yet been adapted for pregnant women with the aim of addressing prenatal mental health. The purpose is thus to evaluate the feasibility, acceptability, and clinical outcomes of an adapted MBSR program, prenatal MBSR, compared to usual care to inform a randomized controlled trial.

Methods/design
Pregnant women (n = 60) referred to an outpatient clinic at Copenhagen University Hospital, Amager and Hvidovre, Denmark, will be recruited for the study. The design is a single-center feasibility trial, with prenatal MBSR, as an add-on to usual care. The primary outcome is to assess the feasibility of a full-scale randomized controlled trial. The secondary feasibility outcome includes possible effects of the adapted MBSR program estimated by self-report questionnaires measuring stress, anxiety, depression, well-being, decentering, reflective functioning, mindfulness, and compassion. Participants will be randomized in a 1:1 ratio to prenatal MBSR or usual care.

Discussion
The study is part of the Good Start to Family Life study anchored at Copenhagen University Hospital, Amager and Hvidovre, Denmark. Teaching the skills of mindfulness meditation to a psychosocially vulnerable group of pregnant women could prove a viable and non-pharmacological approach to reduce stress, improve mental health, and provide support in the transition to parenthood. The outcomes of the feasibility study will inform the design of a fully powered randomized controlled trial.

Trial registration
ClinicalTrials.gov, NCT04571190. Registered on September 30, 2020
How to objectively assess and observe maladaptive pain behaviors in clinical rehabilitation: a systematic search and review
Authors: Naye Florian , Cachinho Chloé , Tremblay Annie-Pier , Saint-Germain Lavoie Maude , Lepage Gabriel , Larochelle Emma , Labrecque Lorijane , Tousignant-Laflamme Yannick 
Published: June 2021

Abstract
Background
Cognitive-affective factors influence the perception of pain and disability. These factors can lead to pain behaviors (PB) that can persist and become maladaptive. These maladaptive PB will further increase the risk of chronicity or persistence of symptoms and disability. Thus, clinicians must be prepared to recognize maladaptive PB in a clinical context. To date, in the context of assessment in a rehabilitation setting, PB in clinical settings are poorly documented. The main objective of this study was to identify direct observation methods and critically appraise them in order to propose recommendations for practice. As a secondary objective, we explored and extracted the different observable PB that patients could exhibit and that clinicians could observe.

Methods
We conducted a comprehensive review on four databases with a generic search strategy in order to obtain the largest range of PB. For the first objective, a two-step critical appraisal used clinical criteria (from qualitative studies on barriers to implement routine measures) and psychometric criteria (from Brink and Louw critical appraisal tool) to determine which observation methods could be recommended for clinical practice. For the second objective, we extracted PB found in the literature to list potential PB that patients could exhibit, and clinicians could observe.

Results
From the 3362 retrieved studies, 47 met the inclusion criteria for the first objective. The clinical criteria allowed us to select three observation methods. After the psychometric step, two observation methods were retained and recommended for clinical practice: the Behavioral Avoidance Test-Back Pain (BAT-Back) and the Pain Behaviour Scale (PaBS). For the second objective, 107 studies met the inclusion criteria. The extraction of the PB allowed us to list a large range of PB and classify the data in 7 categories of PB.

Conclusion
Our results allowed us to recommend two observation methods for clinical practice. However, these methods have limitations and are validated only in chronic low back pain populations. With the extraction of PB presented in the literature, we contribute to better prepare clinicians to recognize PB in all patients who are experiencing pain.
Cannabis use frequency, route of administration, and co-use with alcohol among older adults in Washington state
Authors: Subbaraman Meenakshi S. , Kerr William C. 
Published: June 2021

AbstractBackgroundThe US national surveys and data from legal adult use cannabis states show increases in the prevalence of cannabis use among older adults, though little is known about their manner of cannabis consumption. Here, we examine cannabis use frequency, routes of cannabis administration, and co-use with alcohol, focusing on adults aged 50–64 and ≥65.MethodsData come from a general population survey conducted January 2014–October 2016 (N=5492) in Washington state. We first estimate prevalence and trends in cannabis frequency, routes of administration, and co-use with alcohol in gender by age groups (18–29, 30–49, 50–64, ≥ 65). To test associations between cannabis frequency, route of administration, and co-use with alcohol, we then use sample-weighted multinomial regression adjusted for gender, race/ethnicity, marital status, education, employment, and survey year. Sampling weights are used so results better represent the Washington state population. Regressions focus on the 50–64 and ≥65 age groups.ResultsAmong men and women 50–64, the prevalence of no cannabis use in the past 12 months decreased significantly (84.2% in 2014 to 75.1% in 2016 for women, 76.8% in 2014 to 62.4% in 2016 for men). Among those who report past-year cannabis use, oral administration and vaping and other routes of administration increased by 70% and 94%, respectively each year. Almost one-third of women aged 50–64 and one-fifth of women aged ≥65 who use cannabis reported daily/near daily use, and more than one-third of men who use cannabis in all age groups reported daily/near daily use, including 41.9% of those ≥65. Among men, the prevalence of edibles, drinks, and other oral forms of cannabis administration went up significantly with age (6.6% among 18–29, 21.5% among ≥65). Vaping and other administration are more strongly related to regular and daily/near daily use than infrequent use among those ≥65. The pattern of associations between cannabis frequency and co-use with alcohol differed for women vs. men.ConclusionsIn a general population representative sample of adults living in a state with legal adult use cannabis, the prevalence of cannabis use increased among those aged 50–64 between 2014 and 2016, the prevalence of daily use is substantial, and oral administration and vaping are increasing.
Patient-related outcomes of patellofemoral arthroplasty: experience of a single center
Authors: Abeysekera W. Y. M. , Schenk W. 
Published: June 2021

AbstractPurposeThe purpose of this prospective study was to present the experience of a single center on patellofemoral arthroplasty, in terms of patient-related outcomes.MethodFrom January 2005 to January 2016, 42 patients with isolated patellofemoral osteoarthritis were treated. The patients were assessed using the Oxford Knee Score preoperatively, and one, five, and eight year(s) after surgery. The data of the patients were analyzed using linear mixed effects models. APvalue of 0.05 was considered statistically significant.ResultsAmong 42 patients who underwent patellofemoral arthroplasty, only 25 patients (31 limbs involved) had records up to 5 years. There was a significant clinical improvement of Oxford Knee Score postoperatively (P < 0.05), lowering the score on average by 10.4 ± 1.5 one year after surgery and 8.9 ± 1.9 five years after surgery. This improvement was independent of the types of implants (P > 0.05), gender (P > 0.05), age (P < 0.05), and body mass index (BMI) (P < 0.05).ConclusionPatellofemoral arthroplasty can significantly improve the knee function, and this improvement is independent of the type of implant, gender, age, and BMI. However, further studies will need to assess the long-term outcomes of PFA.
Transdisciplinary training: what does it take to address today’s “wicked problems”?
Authors: Yeung Euson , Carlin Leslie , Sandassie Samantha , Jaglal Susan 
Published: June 2021

AbstractThere is a growing need to address today’s “wicked problems” seen in issues such as social justice, global climate crisis and endemic health concerns. Wicked problems are those for which there is no single, clear or optimal solution and thus are amenable to transdisciplinary solutions. Working in a transdisciplinary paradigm is thus seen as an increasingly necessary learned skill, and yet there is a dearth of knowledge on how curriculum centred around transdisciplinarity is perceived by those impacted by such curricula. This study examines the attitudes and responses of Aging Gracefully across Environments using Technology to Support Wellness, Engagement and Long Life NCE Inc.’s (AGE-WELL) stakeholders to the concept and role of transdisciplinarity in a training program intended to equip trainees and research staff from a variety of fields to address the “wicked problem” of aging well in Canada. We conducted 15 in-depth interviews with current AGE-WELL members, trainees as well as researchers and mentors, on the subject of designing the best possible training program. Our data illustrate the complexity of curriculum design and implementation to train for transdisciplinarity. We consider ways in which a shift in culture or ethos in academia may be required to pursue a thoroughly transdisciplinary approach to problem-solving. Short of instituting such a radical culture change as transdisciplinarity, however, strategic and conscientious efforts to integrate multiple and diverse perspectives, to attend carefully to communication and to foreground relationship building may well achieve some of the same goals.
Explainable prediction of survival using clinical, molecular, and radiomic profiles in recurrent high-grade glioma patients treated with CAR T-cell therapy.
Authors: Wong Chi Wah , Filippov Aleksandr , Bonjoc Kimberley-Jane C. , Brown Christine , Badie Behnam , Chaudhry Ammar 
Published: June 2021

104 Background: High-grade glioma (HGG) is an aggressive heterogeneous primary CNS neoplasm with high recurrence rate and poor survival. Multiple ongoing clinical trials are leveraging targeted molecular and immunologic therapeutics (e.g., pembrolizumab, Chimeric Antigen Receptor [CAR] T-cell therapy) in effort to improve survival. Explainable predictive models have shown value in identifying biomarkers predictive of treatment response as well as informing prognosis. In this study, we developed an explainable machine learning model leveraging clinical, molecular and radiomic (imaging) features to predict overall survival in patients suffering from HGG treated with CAR T-cell therapy. Methods: In this IRB-approved phase 1 clinical trial, 60 patients (39 males, median age = 49) suffering from HGG underwent surgical resection and CAR T-cell therapy1. All patients underwent baseline MRI scans prior to both surgical resection and CAR T-cell administration in the resection cavity. Using contrast-enhanced T1-weighted MRIs, we segmented the enhancing tumor (ET) and generated radiomic features. For predictive modeling, we incorporated the following features: Age, gender, race, ethnicity, histology, tumor grade (WHO), IL-13 receptor alpha 2 (IL-13Rα2) expression (H score), unifocal or multifocal lesions, tumor location (lobe), shape-based radiomics (tumor volume, surface area, and sphericity). We utilized gradient-boosted tree models to classify whether survival is above or below 180 days with two-loop nested cross-validation. For the inner validation loop, we optimized the model with hyper-parameter tuning. For the outer validation loop, we tested the optimal model on the hold-out data and the predictions were used as survival scores (0 – 1). Larger scores imply better predicted survival. For prediction explanations, we adopted the Shapley additive explanation (SHAP) framework. Results: The outer validation loop Area Under the Receiver Operating Characteristic Curve and Area under the Precision-Recall Curve were 0.76 and 0.81, respectively. Among the top five most important features calculated from SHAP; patients with larger tumor surface area, tumor volume and age have reduced survival scores while patients with larger IL-13Rα2 and tumor sphericity have increased survival scores. We stratified the patients into two distinct prognostic sub-groups (30 patients each group) using the survival scores obtained from the outer loop, with a log-rank test p < 0.01. Conclusions: In patients with HGG treated with CAR T-cell therapy, we found that tumor surface area/volume and age are inversely related to survival while increased IL-13Rα2 expression and tumor sphericity were positive predictor of survival. Our model can potentially be used to optimize clinical trial enrollment through more precise patient screening and treatment planning.