bluuebunny/crossref_metadata_2025_split huggingface dataset:
PRC2 Inhibitors Overcome Glucocorticoid Resistance Driven by NSD2 Mutation in Pediatric Acute Lymphoblastic Leukemia
Authors: Li Jianping , Hlavka-Zhang Julia , Shrimp Jonathan H. , Piper Crissandra , Dupéré-Richér Daphne , Roth Jacob S. , Jing Duohui , Casellas Román Heidi L. , Troche Catalina , Swaroop Alok , Kulis Marta , Oyer Jon A. , Will Christine M. , Shen Min , Riva Alberto , Bennett Richard L. , Ferrando Adolfo A. , Hall Matthew D. , Lock Richard B. , Licht Jonathan D. 
Published: August 2021

Abstract

Mutations in epigenetic regulators are common in relapsed pediatric acute lymphoblastic leukemia (ALL). Here, we uncovered the mechanism underlying the relapse of ALL driven by an activating mutation of the NSD2 histone methyltransferase (p.E1099K). Using high-throughput drug screening, we found that NSD2-mutant cells were specifically resistant to glucocorticoids. Correction of this mutation restored glucocorticoid sensitivity. The transcriptional response to glucocorticoids was blocked in NSD2-mutant cells due to depressed glucocorticoid receptor (GR) levels and the failure of glucocorticoids to autoactivate GR expression. Although H3K27me3 was globally decreased by NSD2 p.E1099K, H3K27me3 accumulated at the NR3C1 (GR) promoter. Pretreatment of NSD2 p.E1099K cell lines and patient-derived xenograft samples with PRC2 inhibitors reversed glucocorticoid resistance in vitro and in vivo. PRC2 inhibitors restored NR3C1 autoactivation by glucocorticoids, increasing GR levels and allowing GR binding and activation of proapoptotic genes. These findings suggest a new therapeutic approach to relapsed ALL associated with NSD2 mutation.

Significance:
NSD2 histone methyltransferase mutations observed in relapsed pediatric ALL drove glucocorticoid resistance by repression of the GR and abrogation of GR gene autoactivation due to accumulation of K3K27me3 at its promoter. Pretreatment with PRC2 inhibitors reversed resistance, suggesting a new therapeutic approach to these patients with ALL.
This article is highlighted in the In This Issue feature, p. 1
Endovascular Treatment for Acute Stroke in Cerebral Amyloid Angiopathy
Authors: Weller Johannes M. , Enkirch Simon Jonas , Bogs Christopher , Braemswig Tim Bastian , Deb-Chatterji Milani , Keil Fee , Kindler Christine , Maywald Sarah , Schirmer Markus D. , Stösser Sebastian , Solymosi Laszlo , Nolte Christian H. , Bode Felix J. , Petzold Gabor C. ,   on behalf of the GSR-ET Investigators†, Alegiani A. , Bangard C. , Behme D. , Berrouschot J. , Boeckh-Behrens T. , Bohner G. , Bormann A. , Braun M. , Dichgans M. , Dorn F. , Eckert B. , Ernemann U. , Fiehler J. , Gerloff C. , Gröschel K. , Hamann G.F. , Henn K.H. , Kastrup A. , Kellert L. , Kraemer C. , Krause L. , Liman J. , Ludolph A. , Petersen M. , Pfeilschifter W. , Poli S. , Reich A. , Roth C. , Röther J. , Siebert E. , Stögbauer F. , Thomalla G. , Thonke S. , Tiedt S. , Trumm C. , Uphaus T. , Wiesmann M. , Wunderlich S. , Zweynert S. 
Published: August 2021

Background and Purpose:
We aimed to compare outcome of endovascular thrombectomy in acute ischemic stroke in patients with and without cerebral amyloid angiopathy (CAA).

Methods:
We included patients with and without possible or probable CAA based on the modified Boston criteria from an observational multicenter cohort of patients with acute ischemic stroke and endovascular thrombectomy, the German Stroke Registry Endovascular Treatment trial. We analyzed baseline characteristics, procedural parameters, and functional outcome after 90 days.

Results:

Twenty-eight (17.3%) of 162 acute ischemic stroke patients were diagnosed with CAA based on iron-sensitive magnetic resonance imaging performed before endovascular thrombectomy. CAA patients were less likely to have a good 90-day outcome (14.3 versus 37.8%). National Institutes of Health Stroke Scale score (adjusted odds ratio, 0.88;
P
<0.001), successful recanalization (adjusted odds ratio 6.82;
P
=0.005), and CAA (adjusted odds ratio 0.28;
P
=0.049) were independent outcome predictors. Intravenous thrombolysis was associated with an increased rate of good outcome (36.3% versus 0%,
P
=0.031) in CAA.

Conclusions:
Endovascular thrombectomy with or without thrombolysis appears beneficial in acute ischemic stroke patients with possible or probable CAA, but is associated with a worse functional outcome.

Registration:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT03356392.
Serum Zinc Levels and Incidence of Ischemic Stroke: The Reasons for Geographic and Racial Differences in Stroke Study
Authors: Mattern Lindsey , Chen Cheng , McClure Leslie A. , Brockman John , Cushman Mary , Judd Suzanne , Kahe Ka 
Published: August 2021

Background and Purpose:
Despite zinc’s role as an antioxidant and anti-inflammatory agent, prospective studies relating zinc levels to ischemic stroke risk are lacking. To examine the association between serum zinc levels and incidence of ischemic stroke in a US population.

Methods:
Using a case–cohort study nested within the Reasons for Geographic and Racial Differences in Stroke cohort, participants were randomly selected from the Reasons for Geographic and Racial Differences in Stroke cohort to generate a sub-cohort (n=2346). All incident ischemic stroke cases as of September 2012 (n=660) were included, with 62 incident cases overlapping in the sub-cohort. Serum zinc levels were measured at baseline. Barlow-weighted Cox’s proportional hazards regression models were used to calculate multivariable-adjusted hazard ratios and the corresponding 95% CI of ischemic stroke by serum zinc levels.

Results:

The median zinc level for the sub-cohort was 121.19 µg/dL (interquartile range, 104.86–140.39 µg/dL). Serum zinc levels were inversely associated with incidence of ischemic stroke after adjustment for potential confounders (quartile 4 versus quartile 1: hazard ratio, 0.78 [95% CI, 0.61–0.98],
P
=0.03 for trend). When stratified by prespecified factors (sex, race, region), only sex showed a significant modification (
P
=0.03 for interaction). The inverse association was more pronounced among females (quartile 4 versus quartile 1: hazard ratio, 0.58 [95% CI, 0.41–0.84],
P
<0.01 for trend) than males (quartile 4 versus quartile 1: hazard ratio, 1.08 [95% CI, 0.78–1.51],
P
=0.92 for trend).

Conclusions:
Serum zinc concentration was inversely associated with incidence of ischemic stroke, especially among women, indicating that low zinc levels may be a risk factor for ischemic stroke.
The Colorless History of Pseudo-Aristotle’s De coloribus
Authors: Devriese Lisa 
Published: August 2021

Abstract
This article examines the medieval reception history of De coloribus. This pseudo-Aristotelian treatise on colors was translated from Greek into Latin in the thirteenth century, but the question of its success and use by contemporary scholars has not yet received any attention. After an examination of its medieval commentary tradition, the marginal glosses, and the first attestations, I conclude that De coloribus was scarcely used in the medieval Latin West, although the translation survived in a significant number of manuscripts. In the second part of the article, I look into some possible explanations for this limited reception history. One of the main factors is the availability of several alternative discussions on color in the Aristotelian corpus as well as in the non-Aristotelian scientific literature.
The Surgeon’s Role in Addressing Racism and Achieving Health Equity
Authors: Dawes Daniel E. , Dunlap Nelson J. , Johnson Shaneeta M. 
Published: August 2021

In the United States, the nation’s health is not an organic outcome. It is not a coincidence that certain groups of people living in the United States experience higher premature death rates or poorer health outcomes than others. For centuries, racial and ethnic as well as geographic differences in health outcomes have been part of the American landscape, so entrenched in society that many people fail to recognize that health inequities were intentionally derived. A national crisis tends to magnify inequities in our society, but even more alarming is the fact that as the country becomes more racially and ethnically diverse in the coming years, the health inequities are projected to worsen if we do not proactively and immediately address them. As we continue to grapple with the lasting impact of the pandemic, it is of vital importance that we utilize this time to acknowledge, understand, and seriously address the health inequities that have historically plagued the country for over 400 years. As the United States works overtime to stem the tide of the COVID-19 pandemic, it must also work equally hard to move in a more equitable, inclusive, and healthier direction, not only because of the more than 83 000 Americans dying prematurely each year but also because of the economic and national security toll it will have if not effectively addressed.
Economic analysis of the ‘Take Charge’ intervention for people following stroke: Results from a randomised trial
Authors: Te Ao Braden , Harwood Matire , Fu Vivian , Weatherall Mark , McPherson Kathryn , Taylor William J , McRae Anna , Thomson Tom , Gommans John , Green Geoff , Ranta Annemarei , Hanger Carl , Riley Judith , McNaughton Harry 
Published: August 2021

Objective: To undertake an economic analysis of the Take Charge intervention as part of the Taking Charge after Stroke (TaCAS) study. Design: An open, parallel-group, randomised trial comparing active and control interventions with blinded outcome assessment Setting: Community. Participants: Adults ( n = 400) discharged to community, non-institutional living following acute stroke. Interventions: The Take Charge intervention, a strengths based, self-directed rehabilitation intervention, in two doses (one or two sessions), and a control intervention (no Take Charge sessions). Measures: The cost per quality-adjusted life year (QALY) saved for the period between randomisation (always post hospital discharge) and 12 months following acute stroke. QALYs were calculated from the EuroQol-5D-5L. Costs of stroke-related and non-health care were obtained by questionnaire, hospital records and the New Zealand Ministry of Health. Results: One-year post hospital discharge cost of care was mean (95% CI) $US4706 (3758–6014) for the Take Charge intervention group and $6118 (4350–8005) for control, mean (95% CI) difference $ −1412 (−3553 to +729). Health utility scores were mean (95% CI) 0.75 (0.73–0.77) for Take Charge and 0.71 (0.67–0.75) for control, mean (95% CI) difference 0.04 (0.0–0.08). Cost per QALY gained for the Take Charge intervention was $US −35,296 (=£ −25,524, € −30,019). Sensitivity analyses confirm Take Charge is cost-effective, even at a very low willingness-to-pay threshold. With a threshold of $US5000 per QALY, the probability that Take Charge is cost-effective is 99%. Conclusion: Take Charge is cost-effective and probably cost saving.
Simultaneous Fat Injection for Nasal Contouring in Orthognathic Patients
Authors: Lonic Daniel , Hsiao Yen-Chang , Huang Jung-Ju , Chang Chun-Shin , Chen Jyh-Ping , Heidekrueger Paul I. , Kehrer Andreas , Prantl Lukas , Lo Lun-Jou , Chen Yu-Ray 
Published: August 2021

Background: Augmentation rhinoplasty with autologous fat grafting is a useful procedure to meet the demand for facial harmonization in the Asian population. We used this procedure during orthognathic surgery to address inadequate dorsum projection. This prospective study was conducted to determine the fat retention rate in patients undergoing simultaneous autologous fat injection augmentation rhinoplasty and orthognathic surgery. Methods: Nineteen patients were treated with simultaneous bimaxillary orthognathic surgery and autologous fat grafting of the nasal dorsum and tip. The paired t test was used to compare the nasal volumes before and at least 6 months after surgery measured by 3-dimensional computer tomography scans. All measurements were performed twice by the same evaluator at least 2 weeks apart for intrarater consistency. Results: Seventeen patients completed the study. The volume means before and after surgery were 22.3 ± 4.6 cm3 and 23.3 ± 4.7 cm3, respectively, with a mean difference of 1.0 ± 0.3 cm3 ( P < .001). The mean retention rate was calculated to be 50.5% ± 7.0% (range: 40.5%-64.7%). Intrarater consistency was high with a Cronbach α of .97 ( P < .001) and .98 ( P < .001), respectively. Conclusion: This prospective study provides objective graft retention measurements for fat injection augmentation rhinoplasty combined with orthognathic surgery. All patients were satisfied with the results and no complications or additional morbidity was noted in the postoperative course. We consider this procedure to be a safe, reliable, and powerful adjunct to improve the aesthetic results of orthognathic surgery.
Interdigital vs Transarticular Lateral Release With Scarf Osteotomy
Authors: Hartenbach Florian , Höger Brigitta , Kristen Karl-Heinz , Trnka Hans-Jörg 
Published: August 2021

Background: We compare the clinical and radiographic outcomes of the interdigital approach vs the medial transarticular approach for lateral release combined with scarf osteotomy. Methods: Seventy-seven feet with moderate to severe hallux valgus underwent scarf osteotomy and lateral soft tissue release, using an interdigital approach (n = 36) vs medial transarticular approach (n = 41). The clinical measurements (range of motion, American Orthopaedic Foot & Ankle Society [AOFAS] score) and radiographic data were evaluated preoperatively and at final follow-up (93-124 months postoperatively). Additionally, the numeric pain rating scale and Foot and Ankle Outcome score [FAOS] were assessed postoperatively. Results: The AOFAS score improved from 60 (q1 = 54, q3 = 70) to 93 (q1 = 85, q3 = 98) in the transarticular group, and from 59 (q1 = 50, q3 = 64) to 95 (q1 = 85, q3 = 100) in the interdigital group. The hallux valgus angle improved from 35.7±6.5 degrees to 15.5±7.6 degrees in the transarticular group, and from 36.0±6.8 degrees to 12.9±13.0 degrees in the interdigital group. The intermetatarsal angle improved from 16.5±2.5 degrees to 6.5±2.7 degrees within the transarticular group and from 17.2±2.5 degrees to 7.3±4.3 degrees in the interdigital group. None of the clinical or radiographic parameters showed any significant differences between the treatment groups. Conclusion: Comparison of outcomes between the interdigital approach and the transarticular approach for lateral soft-tissue release with scarf osteotomy are equally successful. The transarticular approach can thus be considered safe and effective, with the additional benefits of just one scar as opposed to 2. Level of Evidence: Level III, therapeutic.
Cheek-midface lifting with lateral canthoplasy for the repair of complex iatrogenic lower eyelid ectropion
Authors: Kopecký Adam , Rokohl Alexander C , Wawer Matos Philomena A , Němčanský Jan , Heindl Ludwig M 
Published: August 2021

Purpose: To assess the efficiency and safety of cheek-midface lifting for the ophthalmoplastic reconstructive surgical repair of cicatricial lower eyelid malpositions after previously failed surgery. Methods: In two ophthalmoplastic clinics, 14 eyelids of 13 patients underwent transconjunctival cheek-midface lifting. In a retrospective audit, changes in margin-reflex distance 2 (MRD2), snap-back test, the position of the eyelid after surgery including improving of the presurgical scleral show, the overall patient’s satisfaction as well as complications after surgery were recorded. Results: Following transconjunctival cheek-midface lifting, there was a significant improvement of MRD2, snap-back test, and the scleral show ( p < 0.001, respectively). However, in three patients the scleral show persisted despite improved MRD2. All patients were satisfied with the results of the surgery. No post-surgical long-term complications were developed. Conclusion: Cheek-midface lifting can be a useful technique in severe cicatricial lower eyelid ectropion after previously failed surgery and is a safe and effective reconstructive method for ophthalmic surgeons with good cosmetical results and little postoperative long-term complications.
Excellent mid-term outcomes with a hemispheric titanium porous-coated acetabular component for total hip arthroplasty: 7–10 year follow-up
Authors: Yeroushalmi David , Singh Vivek , Maher Nolan , Gabor Jonathan A , Zuckerman Joseph D , Schwarzkopf Ran 
Published: August 2021

Introduction: Third-generation hemispheric, titanium porous-coated (HTPC) acetabular cups have been shown to achieve good biologic fixation through enhanced porous ingrowth surfaces. They also allow for a wide range of bearing options, including polyethylene, dual-mobility, and ceramic liners. The purpose of the study is to review the mid-term clinical outcomes an HTPC acetabular cup with a minimum of 7-year follow-up. Methods: A retrospective, observational study was conducted on all consecutive patients who underwent total hip arthroplasty (THA) with an HTCP acetabular cup at an urban, tertiary referral centre. Descriptive statistics were used describe baseline patient characteristics. Outcomes collected included postoperative complications, survival free of reoperations, and presence of osteolysis at latest imaging follow-up. Implant survival was analysed using the Kaplan-Meier method. Results: 118 cases (114 primary, 4 revision) underwent THA with the HTCP acetabular cup at an average follow-up of 8.16 ± 0.85 years (range 7.02–10.28 years). Mean patient age at the time of surgery was 61.29 ± 12.04 years. All cases utilised a high-molecular-weight polyethylene (HMWPE) liner. None of the acetabular cups showed loosening or migration at the latest follow-up. There were 2 revisions in our study, 1 for abductor mechanism disruption and 1 due to surgical site infection where the acetabular cup was revised. Kaplan-Meier survivorship analysis for all-cause revision at 7 and 10-year follow-up showed a survival rate of 99.1% (95% confidence interval, 94.1–99.9%). Survivorship analysis for aseptic acetabular revision at 10-year follow-up showed a survival rate of 100%. Conclusions: At long-term follow-up, no radiologic and minimal clinical complications were identified in this series. The HTPC acetabular cup system, used in conjunction with a HMWPE liner, demonstrates excellent outcomes and survivorship when compared to earlier mid-term studies published in the literature.
A multicomponent psychosocial intervention among people with early-stage dementia involving physical exercise, cognitive stimulation therapy, psychoeducation and counselling: Results from a mixed-methods study
Authors: Skov Sofie S , Nielsen Maj Britt D , Krølner Rikke F , Øksnebjerg Laila , Rønbøl Lauridsen Sigurd M 
Published: August 2021

Background There is increasing awareness of the benefits of both physical and psychosocial interventions to empower and benefit people with dementia and their caregivers. However, the potential additional benefits of combining physical and psychosocial interventions have only been sparsely explored. The aim of this pilot study was to investigate the acceptability and potential impact of a multicomponent intervention comprising physical exercise, cognitive stimulation therapy (CST), psychoeducation and counselling for people with early-stage dementia. Design A 15-week multicomponent group-based intervention was offered to people with early-stage dementia in Denmark ( N = 44). A mixed-methods design combining interviews, observations, tests of cognitive and physical functioning and an interviewer-assisted questionnaire on quality of life was applied to (1) investigate acceptability of the intervention, including whether people with dementia and their caregivers found the intervention meaningful and (2) to explore and assess changes in participants’ physical and cognitive functioning and quality of life. The study was conducted between June 2018 and August 2019. Results The pilot study demonstrated that the multicomponent intervention was acceptable for people with early-stage dementia and their caregivers. Test results did not show significant changes in measures of participants’ physical and cognitive functioning or quality of life. However, qualitative data revealed that participants perceived the intervention as meaningful and found that it had a positive influence on their physical and social well-being. In addition, interaction and support from peers and staff members was considered important and rewarding. Conclusion This multicomponent intervention constitutes a meaningful and beneficial activity for people with early-stage dementia and their caregivers. It provides an opportunity to engage in social interactions with peers and experience professional support. The study also underlines the importance of providing prolonged and sustainable interventions for people with dementia to maintain personal and social benefits.
Associations of Physical Activity and Exercise with Health-related Outcomes in Patients with Melanoma During and After Treatment: A Systematic Review
Authors: Crosby Brendan J. , Lopez Pedro , Galvão Daniel A. , Newton Robert U. , Taaffe Dennis R. , Meniawy Tarek M. , Warburton Lydia , Khattak Muhammad A. , Gray Elin S. , Singh Favil 
Published: August 2021

Purpose: Although exercise medicine is recommended to counter treatment-related side-effects and improve health-related outcomes of patients affected by different cancers, no specific recommendations exist for patients with melanoma. As a result, we systematically examined the current evidence regarding the effects of physical activity and exercise on objectively-measured and patient-reported outcomes among patients with melanoma. Methods: Searches were conducted in PubMed, CINAHL, EMBASE, SPORTDiscus, and Web of Science databases. This review included published data involving physical activity or exercise and objectively-measured or patient-reported outcomes of patients with cutaneous melanoma. The quality of included studies was assessed using the McMaster University Critical Appraisal Tool for Quantitative Studies. Results: Six studies including 882 patients with melanoma were included. Studies presented heterogeneity of design with 2 cross-sectional surveys, 2 retrospective analyses, and 2 non-randomized intervention trials. No statistically significant change in quality of life, fatigue, physical function, cardiorespiratory fitness, body composition, psychological distress, cognitive function, or treatment-related side-effects were attributable to physical activity or exercise. Importantly, physical activity or exercise during melanoma treatment or into survivorship did not adversely impact patients/survivors. Conclusion: In summary, physical activity or exercise did not adversely impact quality of life, objectively-measured or patient-reported outcomes in patients with melanoma. In addition, there is a paucity of quality studies examining the effects of physical activity or exercise on patients with melanoma throughout the cancer care continuum.