bluuebunny/crossref_metadata_2025_split huggingface dataset:
A neural crest stem cell-like state drives nongenetic resistance to targeted therapy in melanoma
Authors: Marin-Bejar Oskar , Rogiers Aljosja , Dewaele Michael , Femel Julia , Karras Panagiotis , Pozniak Joanna , Bervoets Greet , Van Raemdonck Nina , Pedri Dennis , Swings Toon , Demeulemeester Jonas , Borght Sara Vander , Bosisio Francesca , van den Oord Joost J. , Bempt Isabelle Vanden , Lambrechts Diether , Voet Thierry , Bechter Oliver , Rizos Helen , Levesque Mitch , Leucci Eleonora , Lund Amanda W. , Rambow Florian , Marine Jean-Christophe 
Published: December 2020

SummaryThe ability to predict the future behaviour of an individual cancer is crucial for precision cancer medicine and, in particular, for the development of strategies that prevent acquisition of resistance to anti-cancer drugs. Therapy resistance, which often develops from a heterogeneous pool of drug-tolerant cells known as minimal residual disease (MRD), is thought to mainly occur through acquisition of genetic alterations. Increasing evidence, however, indicates that drug resistance might also be acquired though nongenetic mechanisms. A key emerging question is therefore whether specific molecular and/or cellular features of the MRD ecosystem determine which of these two distinct resistance trajectories will eventually prevail. We show herein that, in melanoma exposed to MAPK-therapeutics, the presence of a neural crest stem cell (NCSC) subpopulation in MRD concurred with the rapid development of resistance through nongenetic mechanisms. Emergence of this drug-tolerant population in MRD relies on a GDNF-dependent autocrine and paracrine signalling cascade, which activates the AKT survival pathway in a Focal-adhesion kinase-(FAK) dependent manner. Ablation of this subpopulation through inhibition of FAK/SRC-signalling delayed relapse in patient-derived tumour xenografts. Strikingly, all tumours that eventually escaped this treatment exhibited resistance-conferring genetic alterations and increased sensitivity to ERK-inhibition. These findings firmly establish that nongenetic reprogramming events contribute to therapy resistance in melanoma and identify a clinically-compatible approach that abrogates such a trajectory. Importantly, these data demonstrate that the cellular composition of MRD deterministically imposes distinct drug resistance evolutionary paths and highlight key principles that may permit more effective pre-emptive therapeutic interventions.
How aspiring principals applied course-based learning to develop school improvement plans
Authors: Bickmore Dana L. , Roberts Maria M. , Gonzales Miguel M. 
Published: December 2020

PurposeSchool improvement planning and implementation is one organizational process by which principals may positively impact school and student outcomes. Limited research, however, has explored how principal preparation programs prepare aspiring leaders for this common school leadership activity. This study examined aspiring principals engaged in the school improvement process by evaluating what they included in their school improvement plans (SIPs) that were developed as part of their field experience.Design/methodology/approachThe authors examined SIPs aspiring principals collaboratively developed as part of their field experience. Using an abductive analysis method, combining both deductive and inductive coding methods, authors examined 77 SIPs in which aspiring principals used school level data in planning.FindingsEach aspiring principal's SIP was contextually specific. No two plans were identical relative to who was targeted for improvement and how the plan was to be implemented, indicating aspiring principals can apply course-based learning and implement important data-driven decision-making skills in field-based school improvement projects.Research limitations/implicationsFindings are exploratory and limited to SIPs developed by aspiring principals in one university program in one large urban school district context. The findings that specific requirements and program structures affected the aspiring principal's school improvement planning process as did the overall school context adds to current understandings of how course-based learning is applied. However, further investigations are needed.Practical implicationsFindings provide evidence of how school leadership preparation programs may impact leadership development relative to skills associated with school improvement planning. The findings also suggest the importance of detailed analysis of aspiring principals school improvement planning as a program evaluation process.Originality/valueThis study was the first to document the content of aspiring principals' field-based SIPS and how skills in data-driven decision-making were applied in a SIP field-based activity.
Study of Langerhans cells and T lymphocytes in vulvar lichen sclerosus lesions
Authors: Bao Yingqiu , Li Ziyuan , Liu Wan , Fu Yu , Lv Jiaqi , Sun Kailv , Chang Jianmin 
Published: December 2020

AbstractBackgroundThe aetiology and pathogenesis of vulvar lichen sclerosus (LS), a chronic inflammatory disease, is not completely clear. It has been found that local cellular immune abnormalities play an important role in the immune mechanism of LS, mainly characterised by abnormal numbers of Langerhans cells in the epidermis and abnormal numbers of dermal T lymphocytes.ObjectiveTo evaluate the densities of Langerhans cells and T‐lymphocyte subpopulations in vulvar LS.MethodsThe density of Langerhans cells in the epidermis, and CD3+, CD4+ and CD8+ T cells in the dermis of seven early‐stage and eight late‐stage cases of vulvar LS were detected with direct immunofluorescence, and compared with 15 normal controls.ResultsThe density of Langerhans cells in the late‐stage group was significantly higher than in the normal group (P = 0.001). The densities of CD3+, CD4+ and CD8+ T lymphocytes in both the early‐ and late‐stage (deeper dermis) groups were higher than in the normal group (P < 0.05). The ratio of CD4+/CD8+T lymphocytes in the early‐stage and normal groups showed no significant difference (P = 0.151), while the late‐stage (deeper dermis) groups decreased significantly compared with early‐stage, late‐stage (upper dermis) and normal groups (P < 0.001).ConclusionThe densities of Langerhans cells, CD3+, CD4+ and CD8+ T cells, and the ratio of CD4+/CD8+T lymphocytes were different in different stages of LS, which supports the important role of cellular immunity in mechanisms of LS.
Microaneurysm density in residual oedema after anti‐vascular endothelial growth factor therapy for diabetic macular oedema
Authors: Yamada Yutaka , Takamura Yoshihiro , Morioka Masakazu , Gozawa Makoto , Matsumura Takehiro , Inatani Masaru 
Published: December 2020

AbstractPurposeTo investigate the relationship between microaneurysm (MA) density and residual oedema after intravitreal injection of an anti‐vascular endothelial growth factor agent for the treatment of diabetic macular oedema (DMO).MethodsPatients with DMO were divided into those with residual oedema (RO) and those with no residual oedema (NRO) by the presence and absence of oedema at 1 month after intravitreal injection of either aflibercept or ranibizumab. We then compared MA density, best corrected visual acuity (BCVA), central retinal thickness (CRT) and size of the severely thickened area, as indicated by a white area (WA) on optical coherence tomography.ResultsWe examined 48 eyes in the RO group and 25 eyes in the NRO group (n = 73). In both groups, the CRT and WA size significantly decreased and BCVA improved at 1 month and thereafter. CRT was significantly higher and BCVA was poor in the RO group at 1 and 3 months, while WA size was larger at 1, 3 and 6 months compared with the NRO group (p < 0.05). The number of injections in the RO group (3.62 ± 1.75) was larger than the NRO group (1.89 ± 0.97; p < 0.0001). At 1 and 6 months, the MA density in the area with persistent oedema was significantly higher than in the area with improved oedema (1 month: p = 0.0001, 6 months: p = 0.029).ConclusionHigh MA density and extensive swelling may be characteristic of RO following treatment for DMO with intravitreal injection of either aflibercept or ranibizumab.
Outcomes of a new 3‐D printing‐assisted personalized macular buckle combined with para plana vitrectomy for myopic foveoschisis
Authors: Zou Jing , Tan Wei , Li Fangling , Zhou Gaofeng , Li Liang , Xiong Siqi , Wang Xianggui , Xu Huizhuo 
Published: December 2020

AbstractPurposeTo describe and evaluate the application of a new 3‐D printing‐assisted personalized macular buckle for patients with myopic foveoschisis (MFS).MethodsTwelve eyes of 12 patients with MFS were included in this study. Preoperative MRI images were subsequently measured after marker implantation and imported into the MIMICS software for the 3‐D reconstruction of a virtual model of an eyeball and a marker. The virtual eyeball model was designed according to the degree of retinoschisis, which was measured using optical coherence tomography preoperatively. A macular buckle was designed using a titanium stent, assisted by 3‐D printing; furthermore, it was surgically placed in combination with pars plana vitrectomy. Visual acuity, axial length and anatomic outcomes were analysed pre‐ and postoperatively.ResultsMacular schisis in all patients was completely resolved after the surgery without any postoperative complications. The mean postoperative best corrected visual acuity (LogMAR) improved significantly from 1.21 to 0.92 during the 6‐month follow‐up period (p < 0.001) and reached 0.9 (p < 0.001) after 2 years. The axial length was significantly shortened during the 2 years postoperatively follow‐up period (p < 0.01). The average axial lengths in all patients decreased from 30.62 mm preoperatively to 29.81 mm 1 month postoperatively and remained around 30.16 mm from 1 year after the surgery.ConclusionThe 3‐D printing technique is useful to predict the indentation height and position of the macular buckle. The 3D‐printing‐assisted macular buckle, in combination with vitrectomy, is an effective, safe and accurate treatment modality for MFS.
Mealtime care and dietary intake in older psychiatric hospital inpatient: A multiple case study
Authors: Flint Kate , Matthews‐Rensch Kylie , Flaws Dylan , Mudge Alison , Young Adrienne 
Published: December 2020

AbstractAimsTo investigate the energy and protein adequacy of meals and dietary intake of older psychiatric inpatients and describe patient and mealtime factors potentially influencing intake.DesignMultiple case studies.MethodsPsychiatric inpatients aged 65 years and older, admitted to a single mental health ward during the 6‐week study period (April–May 2019) were eligible for inclusion. Dietary intake was observed for two consecutive days each week (minimum four observation days). Visual plate waste methods were used to estimate patients’ dietary intake at mealtimes, with energy and protein intake calculated using known food composition data and compared with estimated requirements. Medical records were reviewed weekly to collect information on potential factors related to intake and mealtime care. Data from all sources were first summarized in a case record for within‐case analysis using descriptive statistics, followed by cross‐case analysis.ResultsEight participants (five men, age 67–90 years, two underweight and one overweight, and four requiring some mealtime assistance) had 5–12 days of observation data recorded. Three met their estimated daily energy and protein requirements throughout the study period, while the remaining five participants did not. The main barriers identified as contributing to insufficient energy and protein intake were as follows: missing meals (asleep and treatment); inadequate food provided (insufficiency of the standard hospital menu); and need for increased mealtime assistance.ConclusionPoor dietary intake may be common among older psychiatric patients, suggesting that they may also need nursing and multidisciplinary nutrition care interventions shown to effectively prevent and treat malnutrition in other older inpatient groups.ImpactOlder psychiatric patients experience similar nutrition and mealtime issues to other older inpatients. This study highlights the need for nurses and the multidisciplinary team to ensure patients order and receive adequate food, especially when they miss meals and that they receive proactive mealtime assistance.
Opsonization but not pretreatment of equine macrophages with hyperimmune plasma nonspecifically enhances phagocytosis and intracellular killing ofRhodococcus equi
Authors: Harvey Aja B. , Bordin Angela I. , Rocha Joana N. , Bray Jocelyn M. , Cohen Noah D. 
Published: December 2020

AbstractBackgroundEvidence regarding the efficacy of equine hyperimmune plasma to prevent pneumonia in foals caused byRhodococcus equiis limited and conflicting.HypothesisOpsonization withR. equi‐specific hyperimmune plasma (HIP) will significantly increase phagocytosis and decrease intracellular replication ofR. equiby alveolar macrophages (AMs) compared to normal plasma (NP).AnimalsFifteen adult Quarter Horses were used to collect bronchoalveolar lavage cells.MethodsIn the first experiment, AMs from 9 horses were pretreated (incubated) with either HIP, NP, or media only (control) and then infected with nonopsonizedR. equi. In a second experiment, AMs from 6 horses were infected withR. equieither opsonized with HIP or opsonized with NP. For both experiments, AMs were lysed at 0 and 48 hours and the number of viableR. equiquantified by culture were compared among groups using linear mixed‐effects modeling with significance set atP < .05.ResultsOpsonization with either HIP or NP increased phagocytosis by AMs (P < .0001) and decreased intracellular survival of organisms in AMs (P < .0001). Pretreating AMs with either HIP or NP without opsonizingR. equihad no effects on phagocytosis or intracellular replication.Conclusions and Clinical ImportanceOpsonizingR. equiwith either NP or HIP decreases intracellular survival of organisms in AMs, but the effect does not appear to be enhanced by using HIP. Mechanisms other than effects on AMs must explain any clinical benefits of using HIP over NP to decrease the incidence ofR. equipneumonia in foals.
Interpersonal Resilience Inventory: Assessing positive and negative interactions during hardships and COVID‐19
Authors: Rivers Alannah S. , Sanford Keith 
Published: December 2020

AbstractWhen people face difficult life situations, close interpersonal interactions that are positive (supportive, warm, and intimate) and negative (critical, withdrawing, and unhelpful) can be assessed with the Interpersonal Resilience Inventory and should be distinct from social support indices (structural support and perceived support schema), associated with stress and well‐being, and salient across different stress contexts. Online participants completed the Interpersonal Resilience Inventory when facing family or financial stressors (n = 327) and the COVID‐19 pandemic (n = 180). Confirmatory factor analysis, discrimination, correlations, and models regressing stress and well‐being on positive and negative interactions indicated that scales are distinct and explain unique variance in stress and well‐being beyond general social support. Results highlight the unique function of perceived interactions. This study expands previous medical and couple‐specific work on perceptions of positive and negative interactions by assessing them across important relationships, in two unique stress contexts (family and financial hardships, and COVID‐19), and after controlling for other types of social support (support schemas and structural support). This work is important for building parsimonious theories of perceived interactions that may be generalizable across relationships and stress contexts and may illuminate social support pathways to well‐being.
Prevalence of bipolar disorder in multiple sclerosis: a systematic review and meta-analysis
Authors: Joseph Boney , Nandakumar Aiswarya L , Ahmed Ahmed T , Gopal Neethu , Murad M Hassan , Frye Mark A , Tobin W Oliver , Singh Balwinder 
Published: December 2020

BackgroundMultiple sclerosis (MS) is a chronic disabling, demyelinating disease of the central nervous system and is often associated with psychiatric comorbidities. Some studies suggest increased prevalence of bipolar disorder (BD) in MS.ObjectiveTo conduct a systematic review and meta-analysis assessing the prevalence of BD in adults with MS.MethodsWe registered this review with PROSPERO and searched electronic databases (Ovid MEDLINE, Central, Embase, PsycINFO and Scopus) for eligible studies from earliest inception to October 2020. Prevalence data of BD in adult patients with MS were extracted. Meta-analysis was conducted using random-effects model.FindingsOf the 802 articles that were screened, 23 studies enrolling a total of 68 796 patients were included in the systematic review and meta-analysis. The pooled prevalence rate of BD in patients with MS was 2.95% (95% CI 2.12% to 4.09%) with higher prevalence in the Americas versus Europe. The lifetime prevalence of BD was 8.4% in patients with MS. Subgroup analysis showed a higher prevalence of BD in MS in females (7.03%) than in males (5.64%), which did not reach statistical significance (p=0.53).ConclusionsThis meta-analysis suggests a high lifetime prevalence of BD in patients with MS. Patients with MS should be routinely screened for BD. Further assessment of bipolar comorbidity in MS through prospective studies may help in developing effective management strategies and may improve treatment outcomes in patients with MS.
Low High-Density Lipoprotein Cholesterol and High White Blood Cell Counts
Authors: Harsløf Mads , Pedersen Kasper M. , Nordestgaard Børge G. , Afzal Shoaib 
Published: December 2020

Objective:
Animal studies suggest that HDL (high-density lipoprotein) regulates proliferation and differentiation of hematopoietic stem cells. Using a Mendelian randomization approach, we tested the hypothesis that low HDL cholesterol is associated with high white blood cell counts.

Approach and Results:
We included 107 952 individuals aged 20 to 100 years from the Copenhagen General Population Study with information on HDL cholesterol, white blood cell counts, and 9 genetic variants associated with HDL cholesterol. In multivariable-adjusted observational analyses, HDL cholesterol was inversely associated with white blood cell counts. On a continuous scale, a 1-mmol/L (39 mg/dL) lower HDL cholesterol was associated with 5.1% (95% CI, 4.7%–5.4%) higher leukocytes, 4.5% (95% CI, 4.0%–4.9%) higher neutrophils, 5.7% (95% CI, 5.3%–6.1%) higher lymphocytes, 5.7% (95% CI, 5.3%–6.2%) higher monocytes, 14.8% (95% CI, 13.9%–15.8%) higher eosinophils, and 3.9% (95% CI, 3.1%–4.7%) higher basophils. In age- and sex-adjusted genetic analyses using the inverse-variance weighted analysis, a 1-mmol/L (39 mg/dL) genetically determined lower HDL cholesterol was associated with 2.2% (95% CI, 0.3%–4.1%) higher leukocytes, 4.3% (95% CI, 1.6%–7.1%) higher lymphocytes, 4.3% (95% CI, 2.6%–6.1%) higher monocytes, and 4.8% (95% CI, 1.2%–8.5%) higher eosinophils. Overall, the genetic associations were robust across sensitivity analyses and replicated using summary statistics from the UK Biobank with up to 350 470 individuals.

Conclusions:
Genetic and hence lifelong low HDL cholesterol was associated with high peripheral blood leukocytes, including high lymphocytes, monocytes, and eosinophils. The concordance between observational and genetic estimates and independent replication suggest a potential causal relationship.
SIRT3 (Sirtuin-3) Prevents Ang II (Angiotensin II)–Induced Macrophage Metabolic Switch Improving Perivascular Adipose Tissue Function
Authors: Wei Tong , Gao Jing , Huang Chenglin , Song Bei , Sun Mengwei , Shen Weili 
Published: December 2020

Objective:
Infiltrated macrophages actively promote perivascular adipose tissue remodeling and represent a dominant population in the perivascular adipose tissue microenvironment of hypertensive mice. However, the role of macrophages in initiating metabolic inflammation remains uncertain. SIRT3 (sirtuin-3), a NAD-dependent deacetylase, is sensitive to metabolic status and mediates adaptation responses. In this study, we investigated the role of SIRT3-mediated metabolic shift in regulating NLRP3 (Nod-like receptor family pyrin domain-containing 3) inflammasome activation.

Approach and Results:

Here, we report that Ang II (angiotensin II) accelerates perivascular adipose tissue inflammation and fibrosis, accompanied by NLRP3 inflammasome activation and IL (interleukin)-1β secretion in myeloid SIRT3 knockout (SIRT3
−/
−
) mice. This effect is associated with adipose tissue mitochondrial dysfunction. In vitro studies indicate that the deletion of SIRT3 in bone marrow–derived macrophages induces IL-1β production by shifting the metabolic phenotype from oxidative phosphorylation to glycolysis. Mechanistically, SIRT3 deacetylates and activates PDHA1 (pyruvate dehydrogenase E1 alpha) at lysine 83, and the loss of SIRT3 leads to PDH activity decrease and lactate accumulation. Knocking down LDHA (lactate dehydrogenase A) or using carnosine, a buffer against lactic acid, attenuates IL-1β secretion. Furthermore, the blockade of IL-1β from macrophages into brown adipocytes restores thermogenic markers and mitochondrial oxygen consumption. Moreover, NLRP3 knockout (NLRP3
−/−
) mice exhibited reduced IL-1β production while rescuing the mitochondrial function of brown adipocytes and alleviating perivascular adipose tissue fibrosis.

Conclusions:
SIRT3 represents a potential therapeutic target to attenuate NLRP3-related inflammation. Pharmacological targeting of glycolytic metabolism may represent an effective therapeutic approach.
Effects of HIV Infection on Arterial Endothelial Function
Authors: Stein James H. , Kime Noah , Korcarz Claudia E. , Ribaudo Heather , Currier Judith S. , Delaney Joseph C. 
Published: December 2020

Objective:
To determine the effects of HIV serostatus and disease severity on endothelial function in a large pooled cohort study of people living with HIV infection and HIV− controls.

Approach and Results:

We used participant-level data from 9 studies: 7 included people living with HIV (2 treatment-naïve) and 4 had HIV− controls. Brachial artery flow-mediated dilation (FMD) was measured using a standardized ultrasound imaging protocol with central reading. After data harmonization, multiple linear regression was used to examine the effects of HIV− serostatus, HIV disease severity measures, and cardiovascular disease risk factors on FMD. Of 2533 participants, 986 were people living with HIV (mean 44.4 [SD 11.8] years old) and 1547 were HIV− controls (42.9 [12.2] years old). The strongest and most consistent associates of FMD were brachial artery diameter, age, sex, and body mass index. The effect of HIV+ serostatus on FMD was strongly influenced by kidney function. In the highest tertile of creatinine (1.0 mg/dL), the effect of HIV+ serostatus was strong (β=−1.59% [95% CI, −2.58% to −0.60%],
P
=0.002), even after covariate adjustment (β=−1.36% [95% CI, −2.46% to −0.47%],
P
=0.003). In the lowest tertile (0.8 mg/dL), the effect of HIV+ serostatus was strong (β=−1.90% [95% CI, −2.58% to −1.21%],
P
<0.001), but disappeared after covariate adjustment. HIV RNA viremia, CD4+ T-cell count, and use of antiretroviral therapy were not meaningfully associated with FMD.

Conclusions:
The significant effect of HIV+ serostatus on FMD suggests that people living with HIV are at increased cardiovascular disease risk, especially if they have kidney disease.