bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical Pharmacology and Determinants of Response to UCART19, an Allogeneic Anti-CD19 CAR-T Cell Product, in Adult B-cell Acute Lymphoblastic Leukemia
Authors: Dupouy Sandra , Marchiq Ibtissam , Derippe Thibaud , Almena-Carrasco Maria , Jozwik Agnieszka , Fouliard Sylvain , Adimy Yasmina , Geronimi Julia , Graham Charlotte , Jain Nitin , Maus Marcela V. , Mohty Mohamad , Boissel Nicolas , Teshima Takanori , Kato Koji , Benjamin Reuben , Balandraud Svetlana 
Published: November 2022

Background:UCART191 is an “off-the-shelf” genome-edited anti-CD19 chimeric antigen receptor (CAR)-T cell product, manufactured from unrelated healthy donor cells.Methods:UCART19 was administered to 25 adult patients with relapsed or refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL) in the CALM trial. All patients underwent lymphodepletion with fludarabine and cyclophosphamide ± alemtuzumab and received one of three ascending doses of UCART19. Given the allogeneic nature of UCART19, we analyzed the impact of lymphodepletion, HLA disparities, and host immune system reconstitution on its kinetics, along with other factors known to affect autologous CAR-T cell clinical pharmacology.Results:Responder patients (12/25) had higher UCART19 expansion (Cmax) and exposure (AUCTlast) than nonresponders (13/25), as measured by transgene levels in peripheral blood. The persistence of CAR+ T cells did not exceed 28 days in 10/25 patients and lasted beyond 42 days in 4/25. No significant correlation was found between UCART19 kinetics and administered cell dose, patient and product characteristics or HLA disparities. However, the number of prior lines of therapy and absence of alemtuzumab negatively impacted UCART19 expansion and persistence. Alemtuzumab exposure positively affected IL7 and UCART19 kinetics, while negatively correlating with host T lymphocyte AUC0-28.Conclusions:UCART19 expansion is a driver of response in adult patients with R/R B-ALL. These results shed light on the factors associated with UCART19 kinetics, which remain highly affected by the impact of alemtuzumab on IL7 and host-versus-graft rejection.Significance:First description of the clinical pharmacology of a genome-edited allogeneic anti-CD19 CAR-T cell product showing the crucial role of an alemtuzumab-based regimen in sustaining UCART19 expansion and persistence through increased IL7 availability and decreased host T lymphocyte population.
Mechanistic Modeling of the Interplay Between Host Immune System, IL-7 and UCART19 Allogeneic CAR-T Cells in Adult B-cell Acute Lymphoblastic Leukemia
Authors: Derippe Thibaud , Fouliard Sylvain , Marchiq Ibtissam , Dupouy Sandra , Almena-Carrasco Maria , Geronimi Julia , Declèves Xavier , Chenel Marylore , Mager Donald E. 
Published: November 2022

Chimeric antigen receptor (CAR)-T cell therapies have shown tremendous results against various hematologic cancers. Prior to cell infusion, a host preconditioning regimen is required to achieve lymphodepletion and improve CAR-T cell pharmacokinetic exposure, leading to greater chances of therapeutic success. To better understand and quantify the impact of the preconditioning regimen, we built a population-based mechanistic pharmacokinetic-pharmacodynamic model describing the complex interplay between lymphodepletion, host immune system, homeostatic cytokines, and pharmacokinetics of UCART19, an allogeneic product developed against CD19+ B cells. Data were collected from a phase I clinical trial in adult relapsed/refractory B-cell acute lymphoblastic leukemia and revealed three different UCART19 temporal patterns: (i) expansion and persistence, (ii) transient expansion with subsequent rapid decline, and (iii) absence of observed expansion. On the basis of translational assumptions, the final model was able to capture this variability through the incorporation of IL-7 kinetics, which are thought to be increased owing to lymphodepletion, and through an elimination of UCART19 by host T cells, which is specific to the allogeneic context. Simulations from the final model recapitulated UCART19 expansion rates in the clinical trial, confirmed the need for alemtuzumab to observe UCART19 expansion (along with fludarabine cyclophosphamide), quantified the importance of allogeneic elimination, and suggested a high impact of multipotent memory T-cell subpopulations on UCART19 expansion and persistence. In addition to supporting the role of host cytokines and lymphocytes in CAR-T cell therapy, such a model could help optimizing the preconditioning regimens in future clinical trials.Significance:A mathematical mechanistic pharmacokinetic/pharmacodynamic model supports and captures quantitatively the beneficial impact of lymphodepleting patients before the infusion of an allogeneic CAR-T cell product. Mediation through IL-7 increase and host T lymphocytes decrease is underlined, and the model can be further used to optimize CAR-T cell therapies lymphodepletion regimen.
Incidence of Cerebral Venous Thrombosis: A Population-Based Study, Systematic Review, and Meta-Analysis
Authors: Zhou Lily W. , Yu Amy Y.X. , Ngo Long , Hill Michael D. , Field Thalia S. 
Published: November 2022

Background:
Studying the baseline incidence of cerebral venous thrombosis (CVT) prior to COVID-19 and the limitations of how this has been previously reported in the literature will help improve understanding of this disease and how risks may have changed in the post-COVID era.

Methods:
We examined CVT incidence using linked administrative data in British Columbia, Canada (population 5.2 million). To contextualize our findings, we also examined CVT incidence in the published literature and searched MEDLINE and EMBASE for article titles and abstracts up to Nov 2, 2021 on CVT incidence in adults. We performed abstract screening and full-text review prior to data extraction and explored associations between CVT incidence and year of study, geographic location, and study quality with meta-analyses and meta-regression. A random-effects restricted maximum likelihood model was used. Publication bias was assessed using the Egger tests and using visual inspection of the funnel plot for symmetry.

Results:

There were 554 unique CVT cases (mean age 50.9 years, 55.4% women) in British Columbia from 2000 to 2017; overall annual incidence was 8.7 (95%CI‚ 8.0–9.4) per million. Incidence increased over time in men across the entire study period, and from 2011 to 2017 in women. We identified 22 other studies on CVT incidence before 2020 (21/23 total studies included in meta-analysis). Annual incidence overall was 12.1 (95% CI‚ 9.9–14.3) per million with significant between-study heterogeneity (I
2
98.8%, Qp-value<0.001). There were no significant associations on meta-regression between incidence and study year, study quality score, or gross national income per capita of the study country. Visual inspection of the funnel plot and a significant Egger test (z=2.8,
P
<0.01) suggested possible publication bias.

Conclusions:
Incidence of CVT in Canadian data increased over time but remained lower than in other population-based studies. Significant heterogeneity exists in the literature, which may be subject to publication bias.
How to Revisit the Question of Modernity? Some Propositions
Authors: Blitstein Pablo , Lemieux Cyril , Vartija Devin J. , Sullivan Arianna 
Published: November 2022

Abstract
Often dismissed as evolutionism and sometimes accused of maintaining neocolonial domination, the field of studies dedicated to modernity and processes of modernisation has been progressively discredited in the social sciences over the last forty years. However, for some time now, a number of historians and sociologists have sought to rehabilitate this field on new grounds. Rejecting both the miserabilist and populist approaches that have held the monopoly on studies of modernity for too long, their work outlines a research program whose coherence and main arguments are presented in this article. We show that this research program proposes a properly methodological definition of modernity – as the present of humanity – and imposes four major conditions on the study of modernity and processes of modernisation: the refusal of state-centrism; an attention to the practical foundations of different conceptions of “modernity”; an adherence to the principle of contemporaneity; and finally, a commitment to anchoring the generalising ambition of the social sciences within a rigorous search for processual analogies.
Performance Evaluation of Force Transducer for the Observation of Sediment Entrainment in Rapidly Varied Flows
Authors: Riaz Muhammad Zain Bin , Yang Shu-Qing , Sivakumar Muttucumaru , Enever Keith , Khalil Usman , Miguntanna Nadeeka Sajeewani 
Published: November 2022

Abstract
Direct measurement of forces within the rough bed layer have been limited by previous spatial-averaging shear force studies. A highly sensitive force transducer assembled with a target sphere was used to measure and record the instantaneous three-dimensional forces of sediment at incipient motion. In the current study, a laser Doppler anemometer, ultrasonic displacement meter, and a force transducer accompanied by video recordings were used to experimentally investigate the incipient motion of sediment. The developed experimental setup have the potential to resolve and improve fundamental classical hypotheses regarding the incipient sediment motion. Experiments conducted in a large recirculating flume verified that the force transducer detects instantaneous forces at incipient motion under varies hydrodynamic conditions. Depth time series, instantaneous horizontal, vertical, and lateral forces are presented for dam-break and tidal breaking bores. Evidence suggests that the uplift vertical force plays an important role in destabilizing and in the incipient motion of particles. A sudden decrease in horizontal force was observed in tidal breaking bore due to flow reversal; however, a rapid rise was observed due to initial impact of dam-break bore. Bore velocity seems to have a larger effect on dam-break force than bore height. Furthermore, lateral force has the least influence during tidal breaking bore, while sediment particles are subjected to additional lateral force during dam-break bore.
Managing the Destructive Foreign Body: Water Beads in the Ear (A Case Series) and Literature Review
Authors: Zalzal Habib G. , Ryan Matthew , Reilly Brian , Mudd Pamela 
Published: November 2022

Objective: To characterize our experience with super-absorbent polymer beads placed in the external auditory canal to better understand the damage caused and subsequent management required. Methods: Retrospective chart review of pediatric patients at 2 separate tertiary referral centers. Results: Seven patients were identified as having placed super-absorbent polymer beads in the external auditory canal, 6 of whom required removal under general anesthesia. Three patients did not suffer otologic trauma or hearing loss (average foreign body duration <72 hours). Four patients experienced severe otologic complications (average foreign body duration >1 week), all of whom were treated with otologic drops prior to bead identification. Of this severe complication group, 3 patients had restored hearing after surgical intervention, while 1 patient suffered profound hearing loss secondary to labyrinthitis ossificans. Conclusion: Early recognition of otologic foreign bodies is important, particularly if expansile water-bead is suspected. Depending on timeframe, water beads are highly destructive to the middle ear structures, and most patients will require surgical intervention.
Atmospheric PM2.5 exposure and risk of ischemic heart disease: A systematic review and meta-analysis of observational studies
Authors: Wang Qingli , Cao Jingyan 
Published: November 2022

Fine particulate matter <2.5 μm in diameter (PM2.5) has been validated to associate with cardiovascular diseases (CVD) incidence and mortality. So far, no study has quantitatively evaluated the relationship between the atmospheric PM2.5 exposure and ischemic heart disease (IHD). We conducted a meta-analysis to illustrate the relationship between PM2.5 and IHD. Published articles were systematically searched (until June 2022) from PubMed, EMBASE, Cochrane Library. A random-effect model was performed to summarize the total relative risks (RRs) and 95% confidence intervals (CIs). Meta-analysis was performed using Stata 12.0 software. A total of 28 studies among 23 cohorts (23.38 million individuals and 256256 IHD cases) were included. With PM2.5 increasing 10 μg/m3, the total RRs of IHD incidence and mortality were 1.07 (95% CI: 0.99–1.17), 1.21 (95% CI: 1.15–1.28), respectively. In sub-analyses, our study revealed that the combined RRs of exposure to PM2.5 on IHD mortality in Asian and European population [1.11 (95% CI: 0.93–1.33); 1.06 (95% CI: 1.02–1.11)] were much lower compared with American and Canadian people [1.27 (95% CI: 1.17–1.37); 1.30 (95% CI: 1.24–1.35)]. Furthermore, study duration, size and some adjustments were related with the total RR. Our findings indicated that exposure of an increase in the concentration of atmospheric PM2.5 may increase the risk of IHD incidence and mortality. Further evidence is needed to confirmed the association.
‘Sadly I think we are sort of still quite white, middle-class really’ – Inequities in access to bereavement support: Findings from a mixed methods study
Authors: Selman Lucy E , Sutton Eileen , Medeiros Mirra Renata , Stone Tracey , Gilbert Emma , Rolston Yansie , Murray Karl , Longo Mirella , Seddon Kathy , Penny Alison , Mayland Catriona R , Wakefield Donna , Byrne Anthony , Harrop Emily 
Published: November 2022

Background: Voluntary and community sector bereavement services are central to bereavement support in the UK. Aim: To determine service providers’ perspectives on access to their support before and during the COVID-19 pandemic. Design: Mixed methods study using an explanatory sequential design: (1) Cross-sectional online survey of UK bereavement services; (2) Qualitative interviews with staff and volunteers at selected services. Settings/participants: 147 services participated in the survey; 24 interviews were conducted across 14 services. Results: 67.3% of services reported there were groups with unmet needs not accessing their services before the pandemic; most frequently people from minoritised ethnic communities (49%), sexual minority groups (26.5%), deprived areas (24.5%) and men (23.8%). Compared with before the pandemic, 3.4% of services were seeing more people from minoritised ethnic groups, while 6.1% were seeing fewer. 25.2% of services did not collect ethnicity data. Qualitative findings demonstrated the disproportionate impact of the pandemic on minoritised ethnic communities, including disruption to care/mourning practices, and the need for culturally appropriate support. During the pandemic outreach activities were sometimes deprioritised; however, increased collaboration was also reported. Online provision improved access but excluded some. Positive interventions to increase equity included collecting client demographic data; improving outreach, language accessibility and staff representation; supporting other professionals to provide bereavement support; local collaboration and co-production. Conclusions: Service providers report inequities in access to bereavement support. Attention needs to be paid to identifying, assessing and meeting unmet needs for appropriate bereavement support. Identified positive interventions can inform service provision and research.
Advantages of CT Versus MRI for Preoperative Assessment of Osteochondritis Dissecans of the Capitellum
Authors: Müller Sebastian A. , Müller-Lebschi Julia A. , Shotts Ezekiel E. , Bond Jeffrey R. , Tiegs-Heiden Christin A. , Collins Mark S. , O’Driscoll Shawn W. 
Published: November 2022

Background: Magnetic resonance imaging (MRI) is considered to be the gold standard for imaging of osteochondritis dissecans (OCD). Purpose/Hypothesis: The purpose was to determine the additional value of a preoperative computed tomography (CT) scan in adolescent patients with capitellar OCD of the elbow. Consistent with the fact that OCD is a lesion involving the subchondral bone, the hypothesis was that CT would be superior to MRI for imaging OCD of the capitellum. Study Design: Cohort study (diagnosis); Level of evidence, 3. Methods: All patients being treated surgically for an OCD of the capitellum between 2006 and 2016 at one institution were reviewed for preoperative imaging. A total of 28 patients met the inclusion criteria. Corresponding MRI and CT scans were compared retrospectively. Multiple parameters were recorded, with special emphasis on OCD lesion size, fragmentation, and tilt as well as joint surface integrity, loose bodies, and osteophytes. Results: The OCD lesions were best seen on CT scans, whereas MRI T1-weighted images overestimated and T2-weighted images underestimated the size of defects. A subchondral fracture nonunion was found on CT scans in 18 patients, whereas this was seen on MRI T1-weighted images in only 2 patients ( P < .001) and MRI T2-weighted images in 4 patients ( P < .001). Fragmentation of the OCD fragment was found on CT scans in 17 patients but on MRI scans in only 9 patients ( P = .05). Osteophytes as a sign of secondary degenerative changes were seen on CT scans in 24 patients and were seen on MRI scans in 15 patients ( P = .02). Altogether, only 51 of 89 secondary changes including loose bodies, effects on the radial head and ulnohumeral joint, and osteophytes that were seen on CT scans were also seen on MRI scans ( P = .002). Conclusion: OCD fragmentation and secondary changes were more often diagnosed on CT. These factors indicate OCD instability or advanced OCD stages, which are indications for surgery. In an adolescent who is considered at risk for OCD (baseball, gymnastics, weightlifting, tennis) and who has lateral elbow joint pain with axial or valgus load bearing, CT is our imaging modality of choice for diagnosing and staging OCD of the capitellum.
Arthroscopic Treatment of Symptomatic Discoid Lateral Meniscus and Nondiscoid Meniscus in Adolescent Patients
Authors: Su Lisa , Bennett Abbie , Combs Kristen , Torrez Timothy W. , Pham Derek C. , Jackson Nicholas J. , Bowen Richard E. , Beck Jennifer J. 
Published: November 2022

Background: Discoid lateral meniscus (DLM) is a rare condition. Patient-reported outcomes using validated instruments are underreported in the literature. DLM outcomes have not been directly compared with nondiscoid meniscus (non-DLM) in adolescent patients. Purpose/Hypothesis: This study sought to analyze the difference in patient characteristics, surgical treatment, and patient-reported outcomes for adolescent patients arthroscopically treated for symptomatic DLM and non-DLM pathology. We hypothesized that DLM and non-DLM patient-reported outcomes would be similar. Study Design: Cohort study; Level of evidence, 3. Methods: A retrospective review of patients aged <18 years with symptomatic DLM and non-DLM pathology was completed between 2015 and 2021 at a single academic institution. Chart reviews for patient characteristics and surgical operative indications and technique were completed. Patient-reported outcome scores were prospectively collected preoperatively and at 6 months, 1 year, and 2 years after surgery. Results: Patients in the DLM group (n = 48), when compared with the non-DLM group (n = 45), were younger (12.71 vs 15.78 years, respectively; P < .001) and had lower body mass index (24.53 vs 28.91, respectively; P < .02). Both groups were majority Hispanic and more commonly male (DLM 65% vs non-DLM 60%). All of the DLM patients had surgery on the lateral discoid meniscus (n = 48), whereas the non-DLM group had surgery on the lateral meniscus (n = 37), medial meniscus (n = 7), or both (n = 1). A majority of patients in both groups underwent meniscal repair (DLM 73% and non-DLM 62%), and there was no difference in surgical treatment between groups ( P > .05). A statistically significant improvement was seen in International Knee Documentation Committee (IKDC) and Physical Activity Questionnaire (PAQ) scores from the preoperative assessment to 6 months, 1 year, and 2 years after surgery for both DLM and non-DLM groups ( P < .05). No difference was found in scores between DLM and non-DLM groups, between sexes, or between age groups (<13 years or ≥13 years) ( P > .05). Conclusion: Although patients with DLM were younger and had lower body mass index, the IKDC and PAQ scores were not significantly different between the DLM and non-DLM groups. Both groups showed a significant improvement in scores relative to their preoperative scores. Sex and age did not affect IKDC or PAQ scores.
Effect of Quality of Repair on Clinical and Structural Outcomes of Rotator Cuff Repair
Authors: Go Tae Won , Park Ji Eun , Oh Sohee , Cho Minjoon , Jo Chris Hyunchul 
Published: November 2022

Background: Anatomic repair of a torn rotator cuff tendon on the greater tuberosity (GT) is an important surgical goal in rotator cuff repair. However, few studies have investigated whether the efforts made to maximize coverage of the GT are associated with the clinical and structural outcomes after rotator cuff repair surgery. Purpose: To investigate whether the quality of repair at the time of surgery is associated with clinical and structural outcomes after surgery and to identify factors influencing the quality of repair. Study design: Cohort study; Level of evidence, 3. Methods: Data were retrospectively collected from 141 patients who underwent arthroscopic rotator cuff repair between 2008 and 2016. All repairs were classified according to the amount of postoperative GT coverage: A, complete coverage of the GT (n = 96); B, incomplete coverage, comprising more than half of GT (n = 27); C, incomplete coverage, comprising less than half of the GT (n = 16); and D, exposure of the glenohumeral joint (n = 2). All patients underwent magnetic resonance imaging 1 year after surgery. Clinical outcomes and structural integrity based on Sugaya classification were assessed 2 years and 1 year after surgery, respectively. Preoperative factors associated with the postoperative GT coverage (measured at the close of surgery) were identified using a multivariable proportional odds cumulative logit model. Results: The forward flexion strength in group A (10.3 ± 4.6 lb) was significantly greater than that in group C (6.5 ± 3.7 lb) ( P = .003) 2 years after surgery. The postoperative Constant score in group A (76.6 ± 11.5) was greater than that in group C (66.7 ± 15.6) ( P = .018). The number of cases that showed retearing of the repaired tendon was as follows: group A (5/96; 5.2%), group B (7/27; 25.9%), and group C (10/16; 62.5%). There was no significant difference in the changes of pain visual analog scale scores among groups 2 years after surgery (all P > .05). Also, there was no significant difference in the changes of range of motion in all directions among groups 2 years after surgery (all P > .05). Patients with preoperative GT coverage B included in the postoperative GT coverage groups through surgery were as follows: group A (23/45; 51.1%), group B (17/45; 37.8%), and group C (5/45; 11.1%). Preoperative GT coverage was the only independent factor that was associated with GT coverage in multivariable analysis. Conclusion: Quality of repair, measured as the extent of postoperative GT coverage at the time of surgery, was associated with clinical and structural outcomes after rotator cuff repair surgery.