bluuebunny/crossref_metadata_2025_split huggingface dataset:
P20.13.A AUTOGRAFTED HUMAN CORTICAL SLICE MODEL REVEALS MESENCHYMAL-LIKE TRANSITION IN BRAF-MUTATED GLIOBLASTOMA UNDER TARGETED THERAPY
Authors: Zhang J , Joseph K , Beck J , Schnell O , Ravi V M , Heiland D H 
Published: September 2023

Abstract

BACKGROUND
The emergence of personalized therapy, which targets oncogenic drivers, has provided a novel adjunct to the standard-of-care therapy for glioblastoma, the most common central nervous system malignancy. Among the less frequently observed oncogenic drivers in glioblastoma are mutations in the proto-oncogene B-Raf. Although treatment options for BRAF-mutated malignancies have been extensively investigated, the implications of BRAF and MEK inhibition in gliomas remain ambiguous. In this study, we present a model system designed to predict cellular temporal trajectories, employing human neocortical slice models and patient-derived tumor cells, coupled with spatially resolved and single-cell transcriptomic analyses for comprehensive computational modeling.

MATERIAL AND METHODS
Non-neoplastic cortical tissue was procured from a BRAF(V600E) mutant glioblastoma patient during surgical intervention. The tissue was sectioned and inoculated with autologous glioblastoma cells to establish an ex-vivo personalized brain slice model. To facilitate adequate tumor growth, slices were cultured for seven days with clinically approved BRAF/MEK inhibitors and respective controls. For high-dimensional analysis, the tumor specimen and slices in all treatment conditions were profiled using live cell imaging, spatially resolved transcriptomics (Visium 10X) and single nucleus RNA-sequencing (10X). Advanced computational modeling techniques, encompassing graph neural networks and single-cell deconvolution, were employed to scrutinize the spatio-temporal evolution of the tumor and its microenvironment.

RESULTS
Live cell imaging showed varied treatment responses in tumor growth during culture. Immunofluorescence and immunohistochemistry analyses (using NeuN, GFAP, and Iba-1 cell markers) indicated no toxic effects from drug combinations on the tumor microenvironment. Single nucleus profiling revealed a tumoral trajectory towards induction of mesenchymal-like transcriptional programs under BRAF/MEK inhibition along with up-regulation of alternative receptor tyrosine kinases such as HER2/3 and EGFR. Spatial projection of single cell trajectories using cytospace confirmed the escape mechanism of BRAF/MEK inhibition due to acquisition of anti-inflammatory myeloid cells in close proximity to the tumor niches and enhancement of mesenchymal transcriptional programs. In line with the experimental set-up, we observed a rapid progression of the tumor und BRAF/MEK inhibition in the patient.

CONCLUSION
Our reported model system, employing high-dimensional readouts and advanced computational modeling, showcases a promising avenue to address uncertainties in personalized medicine, emphasizing that conventional oncological drivers may necessitate alternative treatment strategies in central nervous system malignancies.
P21.01.A EPIDEMIOLOGY OF ISCHEMIC LESIONS AFTER RESECTION OF LOW-GRADE GLIOMAS
Authors: Dunås T , Lipatnikova A , Thurin E , Jakola A 
Published: September 2023

Abstract

BACKGROUND
Diffuse low-grade gliomas are slow-growing malignant brain tumors that mainly affect people in their 30s and 40s, usually resulting in death within a decade. The standard treatment is surgery, which has a moderate risk of neurological sequelae. Clinical experience indicates that not all sequels are directly related to the resected area but rather caused by collateral damage, such as tissue- and vascular damages at the surgical site, causing ischemic lesions in the surrounding tissue. In this study, the epidemiology of these lesions is investigated, in terms of how common they are and how they are related to the size, type and location of the tumor.

MATERIAL AND METHODS
One hundred and sixty-six patients who underwent resection for grade II glioma (WHO 2007 or 2016) between 2012 and 2017 at any of nine hospitals in Sweden and Norway and had a postoperative MRI scan including diffusion-weighted imaging within three days after surgery, were included in this study. Lesions were segmented on the b1000 image, using the ADC and T1 image to exclude hyperintense areas caused by other factors than ischemia. Statistical analyses were performed using IBM SPSS Statistics version 27.0 (IBM Corp., Armonk, NY, USA). Analyses were carried out with ischemic lesion size as a continuous variable, and since the volumes were not normally distributed, non-parametric tests were used.

RESULTS
Ischemic lesions were found in 146 out of 166 (88%) cases, the median volume of the segmented lesions was 1.9 ml, with an interquartile range (IQR) of 0.95-4.5 ml. Patients with new or worsened deficits did have significantly larger ischemic volumes than does who did not (1.7 vs 2.8 ml, p=0.03). Ischemic volume was significantly correlated to both pre- and post-operative tumor volume (Spearmans rho = 0.370 and 0.304, p&lt;0.001). No difference in ischemic volume was found between astrocytoma and oligodendroglioma, based on reported histopathologic diagnosis (p=0.43) or molecular status (p=0.44), neither between main tumor local (frontal (60%) vs temporal (19%), parietal (8%) or insular (12%), p&gt;0.37).

CONCLUSION
Ischemic lesions after glioma resection are very common, but mostly small and restricted to a region close to the resection cavity. Large ischemic regions were associated with new or worsened neurological deficits and were mostly found in association with large tumors. More fine-tuned measures might be needed to find potential associations between tumor local and ischemic lesions.
Therapeutic effects of high-dose vitamin C supplementation in patients with COVID-19: a meta-analysis
Authors: Sun Lei , Zhao Jia-Hao , Fan Wen-Yi , Feng Bo , Liu Wen-Wen , Chen Rui-Qin , Ban Chuang , Dang Ao-Gui , Wang Miao , Luo Kang-Ting , Zhou Guo-Yu , Yu Fang-Fang , Ba Yue 
Published: September 2023

Abstract

Context
Coronavirus disease 2019 (COVID-19) could induce the “cytokine storm” due to overactivation of immune system and accompanied by acute respiratory distress syndrome as a serious complication. Vitamin C has been effective in improving lung function of patients by reducing inflammation.

Objective
The aim was to explore the therapeutic effects of high-dose vitamin C supplementation for patients with COVID-19 using meta-analysis.

Data Sources
Published studies were searched from PubMed, Cochrane Library, Web of Science, EMBASE, and China National Knowledge Infrastructure databases up to August 2022 using the terms “vitamin C” and “COVID-19”. Data analyses were performed independently by 2 researchers using the PRISMA guidelines.

Data Extraction
Heterogeneity between the included studies was assessed using I2 statistics. When I2 ≥50%, the random-effects model was used; otherwise, a fixed-effects model was applied. Stata 14.0 software was used to pool data by standardized mean differences (SMDs) with 95% CIs or odds ratios (ORs) with 95% CIs.

Data Analysis
The 14 studies had a total of 751 patients and 1583 control participants in 7 randomized controlled trials and 7 retrospective studies. The vitamin C supplement significantly increased ferritin (SMD = 0.272; 95% CI: 0.059 to 0.485; P = 0.012) and lymphocyte count levels (SMD = 0.376; 95% CI: 0.153 to 0.599; P = 0.001) in patients with COVID-19. Patients administered vitamin C in the length of intensive care unit staying (SMD = 0.226; 95% CI: 0.073 to 0.379; P = 0.004). Intake of vitamin C prominently alleviate disease aggravation (OR = 0.344, 95%CI: 0.135 to 0.873, P = 0.025).

Conclusions
High-dose vitamin C supplementation can alleviate inflammatory response and hinder the aggravation of COVID-19.
Outcomes in Premenopausal Patients with HR+/HER2− Breast Cancer and Lymph Node Micrometastasis Based on the 21-Gene Recurrence Score
Authors: Bilani Nadeem , Patel Rima , Crowley Fionnuala , Tiersten Amy 
Published: September 2023

Abstract

Background
Postmenopausal patients with hormone receptor positive, HER2-negative (HR+/HER2−) early breast cancer (EBC) and 21-gene OncotypeDX (ODX) recurrence scores (RS) &lt;26 do not benefit from chemoendocrine therapy (“CET”) compared to endocrine monotherapy (“E”), regardless of nodal status. In premenopausal patients, nodal status is significant in interpretation of RS. However, guidelines are not explicit in recommendations for patients with micrometastasis (“pN1mi” staging).

Methods
A cohort of patients aged &lt;50 years with HR+/HER2− EBC who underwent ODX testing was identified within the National Cancer Database 2004-2019 dataset. We confirmed the prognostic value of ODX in pN1mi disease with multivariate Cox regression for overall survival (OS). We explored how patterns of practice differed by nodal status in cases of low RS (&lt;26) with chi-squared testing. Finally, we performed Kaplan-Meier models comparing OS for those with RS &lt;26 receiving E versus CET, controlling for nodal status.

Results
Of 72 068 patients aged &lt;50 years with HR+/HER2− EBC, 6.1% (n = 4402) had micrometastasis. Multivariate Cox regression confirmed prognostic value of ODX in this pN1mi cohort (P &lt; .001). In the context of RS &lt;26, CET was used most commonly in patients with 1-3 involved lymph nodes (“pN1a-c” disease), less frequently in pN1mi disease, and least in node-negative (“pN0”) disease. A benefit in OS was observed in cases with RS &lt;26 and pN1a-c receiving CET vs. E (P = .017), but not in pN1mi (P = .49) or pN0 (P = .57) disease.

Conclusion
Our large registry analysis found CET was associated with improved OS in pN1a-c, but not in pN1mi or pN0 disease.
A Bayesian spatiotemporal approach to modelling arboviral diseases in Mexico
Authors: Bukhari Moeen Hamid , Shad Muhammad Yousaf , Nguyen Uyen-Sa D T , Treviño C Jesús A , Jung Woojin , Bajwa Waheed U , Gallego-Hernández Ana Lucía , Robinson Renee , Corral-Frías Nadia Sarai , Hamer Gabriel L , Wang Penghua , Annan Esther , Ra Chaelin K , Keellings David , Haque Ubydul 
Published: September 2023

ABSTRACT

Background
The objective of this study was to evaluate the spatial and temporal patterns of disease prevalence clusters of dengue (DENV), chikungunya (CHIKV) and Zika (ZIKV) virus and how socio-economic and climatic variables simultaneously influence the risk and rate of occurrence of infection in Mexico.

Methods
To determine the spatiotemporal clustering and the effect of climatic and socio-economic covariates on the rate of occurrence of disease and risk in Mexico, we applied correlation methods, seasonal and trend decomposition using locally estimated scatterplot smoothing, hotspot analysis and conditional autoregressive Bayesian models.

Results
We found cases of the disease are decreasing and a significant association between DENV, CHIKV and ZIKV cases and climatic and socio-economic variables. An increment of cases was identified in the northeastern, central west and southeastern regions of Mexico. Climatic and socio-economic covariates were significantly associated with the rate of occurrence and risk of the three arboviral disease cases.

Conclusion
The association of climatic and socio-economic factors is predominant in the northeastern, central west and southeastern regions of Mexico. DENV, CHIKV and ZIKV cases showed an increased risk in several states in these regions and need urgent attention to allocate public health resources to the most vulnerable regions in Mexico.
Lens epithelial cell‐derived exosome inhibits angiogenesis in ocular pathological neovascularization through its delivery of miR‐146a‐5p
Authors: Pan Ting , Wu Yan , Zhang Xu , Wang Jingfan , Wang Xingxing , Gu Qinyuan , Xu Changlin , Fan Yuanyuan , Li Xinsheng , Xie Ping , Liu Qinghuai , Hu Zizhong 
Published: September 2023

AbstractAbnormal ocular neovascularization, a major pathology of eye diseases, leads to severe visual loss. The role of lens epithelial cell (LEC)‐derived exosomes (Lec‐exo) is largely unknown. Thus, we aimed to investigate whether Lec‐exo can inhibit abnormal ocular neovascularization and explore the possible mechanisms. In our study, we proved the first evidence that exosomes derived from LECs attenuated angiogenesis in both oxygen‐induced retinopathy and laser‐induced choroidal neovascularization mice models. Further in vitro experiments proved that Lec‐exo inhibited proliferation, migration, and tube formation capability of human umbilical vein endothelial cells in high glucose condition. Further high‐throughput miRNAs sequencing analysis detected that miR‐146a‐5p was enriched in Lec‐exo. Mechanistically, exosomal miR‐146a‐5p was delivered to endothelial cells and bound to the NRAS coding sequence, which subsequently inactivated AKT/ERK signaling pathway. We successfully elucidated the function of Lec‐exo in inhibiting abnormal ocular neovascularization, which may offer a promising strategy for treatment of abnormal ocular neovascularization.
Perioperative Malnutrition
Authors: Booth Alexander T. , Curran Thomas 
Published: September 2023

CASE SUMMARY:
A 61-year-old man presented with penetrating Crohn’s ileocolitis and neoterminal ileal fibrostenotic stricture. He developed an anastomotic leak after a redo ileocolic resection and now has a chronic low-output enterocutaneous fistula. He was transferred from an outside institution for further management and is currently without Crohn’s disease (CD)–related medical therapy. The fistula output is 25 to 50 mL/day of GI contents. His weight dropped by 25 pounds in 6 months after surgery with a current BMI of 19.1, albumin of 2.0 g/dL, and hemoglobin of 9.7 g/dL. During a 3-month period, he was optimized for surgery with local wound care, initiation of infliximab, and nutritional support with exclusive enteral nutrition (EEN). He gained 9 pounds (BMI 20.4). Albumin improved to 3.4 g/dL and hemoglobin to 12.1 g/dL. He underwent a successful open takedown of the enterocutaneous fistula with ileocolic anastomosis.
The association between Helicobacter pylori infection and inflammatory bowel disease in children: A systematic review with meta-analysis
Authors: Kong Guiping , Liu Zhifeng , Lu Yan , Li Mei , Guo Hongmei 
Published: September 2023

Background:
Available literature has reported the association of Helicobacter pylori (H pylori) infection with inflammatory bowel disease (IBD) in adults. However, only a few studies have addressed the disease in children.

Aim:
To ascertain the correlation of H pylori infection with IBD among children.

Methods:
The aim of this systematic review and meta-analysis is to assess the association between H pylori infection and IBD in children. We searched databases including Cochrane, EMBASE, Google Scholar, PubMed, Medline, and Web of Science to select relevant studies. Ultimately, based on predetermined inclusion criteria, we included 6 studies that met the requirements. Review Manager and Stata software were used to extract and analyze the data from the relevant studies. In the methods, we employed both qualitative and quantitative approaches for comprehensive analysis. Qualitative analysis involved describing study designs, sample characteristics, and results, while quantitative analysis involved statistical tests such as calculating pooled risk ratios and 95% confidence intervals to evaluate the association between H pylori infection and IBD in children. Lastly, by combining the results of the individual studies, our objective is to provide a comprehensive understanding of the relationship between H pylori infection and IBD in children.

Results:
In totality, we involved 2236 participants that were recruited in 6 studies. We detected no significant difference in H pylori prevalence (9.8% vs 12.7%, P = .12) by comparing the children IBD group to controls. Among the IBD children, we estimated odds ratio (OR) of H pylori infection to 0.62 [(95% confidence interval (CI) of 0.34–1.12)]. In children suffering from ulcerative colitis (UC) and Crohn disease (CD), the H pylori infection rates were higher than in those with IBD-unclassified (IBDU).When analyzed stratified by disease of study design, In CD group [OR = 1.42, 95% CI: 0.72–2.80)] (I
2 = 0%, P = .64). but no significant difference in CD group.

Conclusions:
No correlation was found between H pylori infection and the occurrence of IBD in children.
Electroencephalography-based parietofrontal connectivity modulated by electroacupuncture for predicting upper limb motor recovery in subacute stroke
Authors: Li Mingfen , Zheng Su , Zou Weigeng , Li Haifeng , Wang Chan , Peng Li 
Published: September 2023

Background:
Predicting motor recovery in stroke patients is essential for effective rehabilitation planning and goal setting. However, intervention-specific biomarkers for such predictions are limited. This study investigates the potential of electroacupuncture (EA) – induced brain network connectivity as a prognostic biomarker for upper limb motor recovery in stroke.

Methods:
A randomized crossover and prospective observational study was conducted involving 40 stroke patients within 30 days of onset. Patients underwent both EA and sham electroacupuncture (SEA) interventions. Simultaneously, resting electroencephalography signals were recorded to assess brain response. Patients’ motor function was monitored for 3 months and categorized into Poor and proportional (Prop) recovery groups. The correlations between the targeted brain network of parietofrontal (PF) functional connectivity (FC) during the different courses of the 2 EA interventions and partial least squares regression models were constructed to predict upper limb motor recovery.

Results:
Before the EA intervention, only ipsilesional PF network FC in the beta band correlated with motor recovery (r = −0.37, P = .041). Post-EA intervention, significant correlations with motor recovery were found in the beta band of the contralesional PF network FC (r = −0.43, P = .018) and the delta and theta bands of the ipsilesional PF network FC (delta: r = −0.59, P = .0004; theta: r = −0.45, P = .0157). No significant correlations were observed for the SEA intervention (all P > .05). Specifically, the delta band ipsilesional PF network FC after EA stimulation significantly differed between Poor and Prop groups (t = 3.474, P = .002, Cohen’s d = 1.287, Poor > Prop). Moreover, the partial least squares regression model fitted after EA stimulation exhibited high explanatory power (R
2 = 0.613), predictive value (Q
2 = 0.547), and the lowest root mean square error (RMSE = 0.192) for predicting upper limb proportional recovery compared to SEA.

Conclusion:
EA-induced PF network FC holds potential as a robust prognostic biomarker for upper limb motor recovery, providing valuable insights for clinical decision-making.
Sorafenib exhibits lower toxicity and comparable efficacy to sunitinib as a first-line treatment for metastatic renal cell carcinoma: A systematic review and meta-analysis
Authors: Li Dailong , Wan Sha , Li Wanqiang , Cheng Chunlai , Xu Lu , Gu Peng 
Published: September 2023

Background:
To assess the safety and efficacy of sorafenib and sunitinib as first-line treatments for metastatic renal cell carcinoma (mRCC), to provide evidence-based support for clinical decision-making regarding rational drug use.

Methods:
Until May 10, 2023, a comprehensive search was conducted across PubMed, EMBASE, Cochrane Library, ClinicalTrials.gov, China National Knowledge Infrastructure, and Wanfang databases to identify clinical studies comparing sorafenib with sunitinib as first-line treatment for mRCC. The literature was screened, data extracted, and quality evaluated independently by 2 researchers. Meta-analysis was conducted using Revman5.4 software.

Results:
A total of 3741 patients were enrolled in 20 studies. The meta-analysis results indicated that there were no significant differences in the 2- and 5-year progression-free survival (PFS) and overall survival (OS) rates between the sorafenib and sunitinib groups (P > .05). The disease control rate (DCR) was comparable between the 2 groups (P > .05), while the objective response rate (ORR) was higher in the sunitinib group (P = .03). However, subgroup analysis revealed no significant differences in ORR, DCR, 2- and 5-year PFS, and OS rates between sorafenib and sunitinib among both Asian populations as well as European and American populations (P > .05). In terms of drug-related adverse events, the incidence of grade ≥ 3 hypertension, leukopenia, neutropenia, thrombocytopenia, anemia, nausea and vomiting were significantly lower in the sorafenib group compared to the sunitinib group (P < .05).

Conclusion:
In the first-line treatment of mRCC, sorafenib exhibits comparable efficacy to sunitinib but with lower toxicity.
Effectiveness and safety of non-vitamin K antagonist oral anticoagulant in the treatment of patients with morbid obesity or high body weight with venous thromboembolism: A meta-analysis
Authors: Zhang Hongxia , Xie Hua , Wang Xiaoyan , Zhu Zonghong , Duan Feng 
Published: September 2023

Background:
Venous thromboembolism (VTE) poses a significant health risk to patients with morbid obesity or high body weight. Non-vitamin K antagonist oral anticoagulants (NOACs) are emerging treatments, but their effectiveness and safety compared with vitamin K antagonists (VKAs) in this population are yet to be thoroughly studied.

Methods:
We conducted a systematic review and meta-analysis, adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Four electronic databases were searched for relevant studies comparing the efficacy and safety of NOACs and VKAs in treating patients with VTE with a body mass index > 40 kg/m2 or body weight > 120 kg. Eligible studies were scored for quality using the Newcastle-Ottawa Scale.

Results:
Thirteen studies were included. The meta-analysis results showed that compared to VKAs, NOACs significantly decreased the risk of VTE occurrence (odds ratio = 0.72, 95% CI: 0.57–0.91, I
2 = 0%, P < .001) and were associated with a lower risk of bleeding (odds ratio = 0.74, 95% CI: 0.58–0.95, I
2 = 0%, P < .05). Subgroup analysis showed that in the cancer patient subgroup, both risks of VTE occurrence and bleeding were lower in the NOAC group than in the VKA group. In patients without cancer, the risk of VTE was significantly lower in the NOAC group.

Conclusion:
NOACs appear to be more effective and safer than VKAs in patients with morbid obesity or a high body weight with VTE. However, further large-scale randomized controlled trials are required to confirm these findings.
Managing Older Adults' Chronic Pain
Authors: Arnstein Paul , Shade Marcia , Herr Keela A. , Young Heather M. , Fishman Scott M. 
Published: September 2023

This article is part of a series, Supporting Family Caregivers: No Longer Home Alone, published in collaboration with the AARP Public Policy Institute. Results of focus groups, conducted as part of the AARP Public Policy Institute's No Longer Home Alone video project, supported evidence that family caregivers aren't given the information they need to manage the complex care regimens of family members. This series of articles and accompanying videos aims to help nurses provide caregivers with the tools they need to manage their family member's health care at home.
This new group of articles provides practical information nurses can share with family caregivers of persons living with pain. To use this series, nurses should read the articles first, so they understand how best to help family caregivers. Then they can refer caregivers to the informational tear sheet—Information for Family Caregivers—and instructional videos, encouraging them to ask questions. For additional information, see Resources for Nurses. Cite this article as: Arnstein, P., et al. Managing Older Adults' Chronic Pain: Higher-Risk Interventions. Am J Nurs 2023; 123 (4): 56-61.