bluuebunny/crossref_metadata_2025_split huggingface dataset:
OTME-9. Comprehensive Metabolic Profiling Of high MYC Medulloblastoma Reveals Key Differences Between In Vitro And In Vivo Glucose And Glutamine Usage
Authors: Pham Khoa , Poore Brad , Hanaford Allison , Maxwell Micah J , Sweeney Heather , Parthasarathy Akhila , Alt Jesse , Rais Rana , Slusher Barbara S , Eberhart Charles G , Raabe Eric H 
Published: July 2021

Abstract
Reprograming of cellular metabolism is a hallmark of cancer. The metabolic alterations in cancer cells is not only defined by series of genetic mutations, but also reflecting the crosstalk between cancer cells and other factors in the microenvironment. Altering metabolism allows cancer cells to overcome unfavorable conditions, to proliferate and invade. Medulloblastoma is the most common malignant brain tumor of children. Genomic amplification of MYC is a hallmark of a subset of poor-prognosis medulloblastoma. However, the metabolism of high MYC amplified medulloblastoma subgroup remains underexplored. We performed comprehensive metabolic studies of human MYC-amplified medulloblastoma by comparing the metabolic profiles of tumor cells in different environments – in vitro, in flank xenografts and in orthotopic xenografts. Principal component analysis showed that the metabolic profiles of brain and flank high-MYC medulloblastoma tumors clustered closely together and separated away from normal brain and the high-MYC medulloblastoma cells in culture. Compared to normal brain, MYC-amplified medulloblastoma orthotopic xenograft tumors showed upregulation of nucleotide, hexosamine biosynthetic pathway (HBP), TCA cycle, and amino acid and glutathione pathways. There was significantly higher glucose up taking and usage in orthotopic xenograft tumor compared to flank xenograft and cells in culture. The data demonstrated that glucose was the main carbon source for the glutamate, glutamine and glutathione synthesis through the TCA cycle. The glutaminase ii pathway was the main pathway utilizing glutamine in MYC-amplified medulloblastoma in vivo. Glutathione was found as the most abundant upregulated metabolite. Glutamine derived glutathione was mainly synthesized through glutamine transaminase K (GTK) enzyme in vivo. In conclusion, we demonstrated that high MYC medulloblastoma adapt to different environments by altering its metabolic pathways despite carrying the same genetic mutations. Glutamine antagonists may have therapeutic applications in human patients.
OTME-10. Integrated analysis of human gliomas at the single cell level identifies S100A4 as a novel immunotherapy target
Authors: Abdelfattah Nourhan , Kumar Parveen , Leu Jia-Shiun , Flynn William , Baskin David , Ptichumani Kumar , Ijare Omkar , George Joshy , Yun Kyuson 
Published: July 2021

Abstract
Understanding the immune composition of a given tumor is critical to assess its potential responsiveness to cancer immunotherapy. This is especially true for tumors that are intrinsically resistant to immunotherapies, such as GBM. Unfortunately, studies on the functional heterogeneity and associated molecular targets of immune-suppressive cells in vivo have been lacking. Here we report an integrated multi-dimensional analysis of the mutational profiles and single-cell transcriptomics of 60,024 glioma and stromal cells from 16 human samples. We identified molecular signatures of seven distinct macrophage subtypes, each with prognostic clinical value. The three inflammatory subtypes showed hallmarks of TNF/NFκB pathway enrichment and are associated with good outcomes; in contrast, four immunosuppressive subtypes with metabolic pathway hallmarks (oxidative phosphorylation, PI3K/AKT/mTOR, fatty acid metabolism) are associated with poor survival. In addition, we resolved an ongoing controversy in the field regarding the roles of brain resident macrophages, microglia, vs. bone marrow derived macrophages (BMDM) in gliomas. Our data show compelling evidence that microglia are pro-inflammatory and are associated with good survival while BMDMs are mostly immune-suppressive and associated with poor survival. In addition, deciphering immune-suppressive macrophage and Treg molecular signatures enabled us to identify previously unknown immunotherapy targets. In a proof of principle study, we showed that S100A4, a calcium binding protein previously shown to mediate metastasis, was universally upregulated in both innate and adaptive immune suppressor cells, and implantation of gliomas in S100a4-/- host mice significantly extended survival and resulted in pro-inflammatory immune landscape, compared to same glioma cells implanted in B6 control hosts. This functional validation study shows that S100A4 is a highly promising therapeutic target for GBM immunotherapy.
The association between sugar intake during pregnancy and allergies in offspring: a systematic review and a meta-analysis of cohort studies
Authors: Gupta Adyya , Singh Ankur , Fernando Roshan L , Dharmage Shyamali C , Lodge Caroline J , Waidyatillake Nilakshi T 
Published: July 2021

Abstract

Context
It has been hypothesized that a mother’s diet during pregnancy may modulate her offspring’s immune system development and lead to development of allergic diseases among offspring. However, the evidence for this is unclear and inconclusive.

Objective
This systematic review was undertaken to examine the weight of evidence for causality from cohort studies on the association between maternal free sugar intake during pregnancy and development of allergies in offspring.

Data Sources
Using a systematic search strategy, PubMed, SCOPUS, and Web of Science databases were searched from inception to May 2020.

Data Extraction
For the reporting of this systematic review, the PRISMA guideline was followed. Studies examining maternal sugar consumption during pregnancy (using self-reported data) and the development of allergic diseases among offspring (infancy to 5 years) were included.

Data Analysis
The Newcastle–Ottawa Scale quality assessment tool was used to assess the study quality. Meta-analysis was conducted using a random-effects model to synthesize the findings. Of 159 publications identified from the search, 5 articles with 4 unique cohort studies were included in this systematic review. The limited meta-analysis showed that a mother’s increased free sugar intake during pregnancy was associated with an increased risk of developing asthma in offspring (odds ratio 1.07 [95% CI, 1.00 to 1.14; I2 = 0%]). High free sugar intake by the mother during pregnancy was also associated with increased odds of offspring (to age 7.7 years) developing other common allergies, including allergic rhinitis, atopy and eczema, wheeze, and food allergies .

Conclusion
From the limited evidence, this review suggests that high free sugar consumption during pregnancy may be associated with the development of allergies in offspring. Clinical guidelines and public health policy recommendations for maternal diet in pregnancy should include advice about reducing free sugar intake due to a possible association with allergies in offspring. However, recommendations should be made with caution considering other maternal and fetal risk factors.
Evaluation of rice research: An alternate method to capture outcomes
Authors: Samal Parshuram , Mondal Biswajit , Jambhulkar Nitiprasad N , Singh Onkar N , Verma Ramlakhan , Dash Sushant K , Das Anup K , Pathak Himanshu 
Published: July 2021

AbstractPolicy-makers, research managers, and donors are interested in knowing the outputs, outcomes, and impacts of investment in agricultural research. Several institutions are engaged in rice research and impact assessment of rice research requires area coverage information for rice varieties. The area coverage information for individual varieties is not available at the national level in many developing countries as the conventional household survey method is expensive and time-consuming. This article aims to find a cost-effective and quick method to estimate the area under popular rice varieties in India and their spread in different states. Secondary data collected from 27 states and 1 union territory of India were used to estimate the area. The results of the new method compared well with some of the studies conducted at the state level. The most important varieties identified using the new method were Swarna, Cottondora Sannalu, Samba Mahsuri, Vijetha, IR-64, and Ranjeet, which covered more than 1 million ha each in the country. On geographical coverage, IR-64 has spread to 17 states followed by Swarna, Cottondora Sannalu, Samba Mahsuri, Vijetha, IR-36, and Swarna Sub-1 which covered 14, 14, 12, 11, 11, and 10 states, respectively. The area information can be used to compute returns to rice research by different research institutions and study dynamics of varietal change over time. The popular varieties identified should be used in future breeding programs and biotechnological studies for the development of superior varieties.
Ultrasound in osteoarthritis of the hand: a comparison to computed tomography and histology
Authors: Husic Rusmir , Finzel Stephanie , Stradner Martin H , Dreu Manuel , Hofmeister Alexander , Beham-Schmid Christine , Graninger Winfried B , Fessler Johannes , Dejaco Christian 
Published: July 2021

Abstract

Objective
To compare structural findings between US, micro-CT (µCT) and histology in people with OA of the hands.

Methods
We analysed DIP and PIP joints of 31 fingers from 15 dissecting-room cadavers with OA of the hands. The occurrence of bone erosions and osteophytes were recorded by US, µCT and histology at 16 regions for each joint and compared for each method.

Results
In total, US (n = 558, 56.2% of 992 examined regions) and µCT (n = 493, 49.7%) detected a higher frequency of osteophytes at PIP and DIP joints than histology (n = 161, 23.4% of 689 histological examined regions; P = 0.01). We found a comparable number of erosions with each method [US, n = 52 (5.2%); µCT, n = 43 (4.3%); histology, n = 35 (5.2%)]. Both imaging techniques correlated moderately with each other regarding the detection of osteophytes (r = 0.54, P = 0.002) and erosions (r = 0.43, P = 0.017). Neither US nor µCT correlated with histology regarding erosions or osteophytes. With histology as the reference, US had a sensitivity of 80% and a specificity of 32% to detect osteophytes, whereas µCT had a sensitivity of 73% and a specificity of 27%. For erosions, sensitivities (US 10% and µCT 6%, respectively) were much lower. Microscopically, erosions contained fibrous myxoid tissue extending from subcortical cavities through the breach of cortical bone.

Conclusions
The ability of US to identify osteophytes was comparable to that of µCT, yielding a good sensitivity when histology was used as the gold standard. The sensitivity of US and µCT to detecting erosions was low compared with histology.
Neonatal Nurse and Midwife Competence Regarding Pain Management in Neonates
Authors: Mala Onanong , Forster Elizabeth M. , Kain Victoria J. 
Published: July 2021

Background:
Neonates in need of intensive care are often subjected to numerous painful procedures. Despite the growing scientific research, hospitalized neonates continue to experience unrelieved pain. Enhancing the competence of neonatal intensive care nurses is an integral component of effective pain management.

Purpose:
The purpose of this article is to identify and synthesize the existing evidence on nurses' and midwives' competence regarding neonatal pain management internationally.

Methods/Search Strategy:
The review was guided by Whittemore and Knafl's 5-stage framework, with 8 databases searched in June 2020 including PubMed, CINAHL Complete (via EBSCOhost), MEDLINE (via EBSCOhost), PsycINFO (via Ovid), EMBASE, Scopus, Cochrane Library, and Google Scholar. Reference lists of selected articles were also hand-searched. Studies were reviewed independently for methodology and inclusion and exclusion criteria. The initial search yielded 3037 articles; 19 met the inclusion criteria and were included for analysis: qualitative (n = 5) and quantitative (n = 14).

Findings/Results:
Nurses' and midwives' competence regarding neonatal pain management in the neonatal intensive care unit is discussed in relation to knowledge, attitudes, behaviors, and perceptions of competence by most studies. The barriers to effective neonatal pain management were found to relate to nurses' and midwives' factors, underutilized pain assessment tools, and organizational factors. Potential facilitators to effective neonatal pain management included clear evidence-based guidelines/protocols, adequate training, and the use of appropriate and accurate pain assessment tools. Parent involvement and a team approach to neonatal pain management were also identified.

Implications for Practice and Research:
These findings suggest that further research is necessary to address the barriers and promote facilitators to improve neonatal pain management.
Comparison of preoperative and postoperative radiation therapy for extremity soft-tissue sarcoma: a randomized clinical trial
Authors: Mahmoudi Hamideh , Arefpour Amir Mohammad , Jamshidi Khodamorad , Fadavi Pedram , Mirzaei Alireza 
Published: July 2021

Background:
The optimal sequencing of radiotherapy and surgery for the treatment of soft-tissue sarcoma (STS) is an ongoing source of controversy. In this study, the authors compared preoperative and postoperative radiotherapy in patients with extremity STS.

Methods:
Eighty patients with localized extremity STS were randomly assigned to either preoperative or postoperative radiotherapy group. Baseline characteristics of the patients were not significantly different between the two study groups. Primary outcome measures were pain, acute complications (wound dehiscence and infection), and late complications (limb edema, subcutaneous fibrosis, and joint stiffness). The severity of late complications was evaluated using the radiation therapy oncology group criteria. Secondary outcome measures were oncologic outcomes, including local recurrence and distant metastasis.

Results:
The mean pain level was not significantly different between the two groups (P=0.1). Infection was not seen in any of the patients. The rate of wound dehiscence and infection was not significantly different between the two groups (P=0.32 for both). Of the late complications, the rate of limb edema and subcutaneous fibrosis was similar in the two groups (P=0.16 and P=0.35, respectively). In contrast, the rate of joint stiffness was significantly more in the postoperative radiotherapy group (P<0.001). The severity of all three late complications also was more in the postoperative radiotherapy group at 6 and 12 mo. There were no significant differences between the two groups regarding local recurrence and distant metastasis (P=0.99 and P=0.77, respectively).

Conclusions:
The authors suggest preoperative radiotherapy in patients with localized extremity STS because of its lower rate of and less severe complications, particularly joint stiffness.

Level of Evidence:
Level I.
Descriptors of Sepsis Using the Sepsis-3 Criteria: A Cohort Study in Critical Care Units Within the U.K. National Institute for Health Research Critical Care Health Informatics Collaborative*
Authors: Shah Anoop D. , MacCallum Niall S. , Harris Steve , Brealey David A. , Palmer Edward , Hetherington James , Shi Sinan , Perez-Suarez David , Ercole Ari , Watkinson Peter J. , Jones Andrew , Ashworth Simon , Beale Richard , Brett Stephen J. , Singer Mervyn 
Published: July 2021

OBJECTIVES:
To describe the epidemiology of sepsis in critical care by applying the Sepsis-3 criteria to electronic health records.

DESIGN:
Retrospective cohort study using electronic health records.

SETTING:
Ten ICUs from four U.K. National Health Service hospital trusts contributing to the National Institute for Health Research Critical Care Health Informatics Collaborative.

PATIENTS:
A total of 28,456 critical care admissions (14,332 emergency medical, 4,585 emergency surgical, and 9,539 elective surgical).

MEASUREMENTS AND MAIN RESULTS:
Twenty-nine thousand three hundred forty-three episodes of clinical deterioration were identified with a rise in Sequential Organ Failure Assessment score of at least 2 points, of which 14,869 (50.7%) were associated with antibiotic escalation and thereby met the Sepsis-3 criteria for sepsis. A total of 4,100 episodes of sepsis (27.6%) were associated with vasopressor use and lactate greater than 2.0 mmol/L, and therefore met the Sepsis-3 criteria for septic shock. ICU mortality by source of sepsis was highest for ICU-acquired sepsis (23.7%; 95% CI, 21.9–25.6%), followed by hospital-acquired sepsis (18.6%; 95% CI, 17.5–19.9%), and community-acquired sepsis (12.9%; 95% CI, 12.1–13.6%) (p for comparison less than 0.0001).

CONCLUSIONS:
We successfully operationalized the Sepsis-3 criteria to an electronic health record dataset to describe the characteristics of critical care patients with sepsis. This may facilitate sepsis research using electronic health record data at scale without relying on human coding.
Development and Validation of A Liquid Chromatography–Tandem Mass Spectrometry Method to Simultaneously Measure Tacrolimus and Everolimus Concentrations in Kidney Allograft Biopsies After Kidney Transplantation
Authors: Zhang Mengyu , Tajima Soichiro , Shigematsu Tomohiro , Noguchi Hiroshi , Kaku Keizo , Tsuchimoto Akihiro , Okabe Yasuhiro , Egashira Nobuaki , Ieiri Ichiro 
Published: July 2021

Background:
Therapeutic drug monitoring is necessary for immunosuppressive therapy with tacrolimus and everolimus after kidney transplantation. Several studies have suggested that the concentrations of immunosuppressive agents in allografts may better reflect clinical outcomes than whole blood concentrations. This study aimed to develop a method for the simultaneous quantification of tacrolimus and everolimus concentrations in clinical biopsy samples and investigate their correlation with histopathological findings in kidney transplant recipients.

Methods:
Fourteen biopsy samples were obtained from kidney transplant recipients at 3 months after transplantation. Kidney allograft concentrations (Ctissue) of tacrolimus and everolimus were measured by liquid chromatography–tandem mass spectrometry, and the corresponding whole blood trough concentrations (C0) were obtained from clinical records.

Results:
The developed method was validated over a concentration range of 0.02–2.0 ng/mL for tacrolimus and 0.04–4.0 ng/mL for everolimus in kidney tissue homogenate. The Ctissue of tacrolimus and everolimus in kidney biopsies ranged from 21.0 to 86.7 pg/mg tissue and 33.5–105.0 pg/mg tissue, respectively. Dose-adjusted Ctissue of tacrolimus and everolimus was significantly correlated with the dose-adjusted C0 (P < 0.0001 and P = 0.0479, respectively). No significant association was observed between the Ctissue of tacrolimus and everolimus and the histopathologic outcomes at 3 months after transplantation.

Conclusions:
This method could support further investigation of the clinical relevance of tacrolimus and everolimus allograft concentrations after kidney transplantation.
Tear Film Surface Quality in Modern Daily Disposable Contact Lens Wear
Authors: Mousavi Maryam , Garaszczuk Izabela K. , De Jesus Danilo Andrade , Szczesna-Iskander Dorota H. , Armstrong Richard A. , Nichols Kelly K. , Iskander D. Robert 
Published: July 2021

Objectives:
As reported previously, tear film surface quality (TFSQ) should be considered in contact lens (CL) fitting. This study followed noninvasive keratograph tear film break-up time (NIKBUT) in CL wearers for 12 months to validate its clinical utility in predicting CL performance.

Methods:
Fifty-five subjects (M/F=17/38) aged 26±4 years were prescribed silicone hydrogel or hydrogel CLs. The study included baseline measurements without CLs; 2 visits for CL fitting and control; follow-up after 3, 6, and 12 months of CL wear; and postwear visit without CLs. Ocular Surface Disease Index (OSDI), 8-Item Contact Lens Dry Eye Questionnaire (CLDEQ-8), first and mean NIKBUT (F/M-NIKBUT), fluorescein tear film break-up time (FBUT), and ocular surface staining were evaluated.

Results:
Post hoc analysis of each pair of visits showed differences between baseline and all CL visits for F-NIKBUT, M-NIKBUT, FBUT, and corneal staining. No difference was reported in symptoms. In addition, differences between baseline and postwear visits were noted in OSDI, M-NIKBUT, FBUT, and corneal staining, with three of the latter parameters showing a downward trend.

Conclusions:
No changes in TFSQ and symptoms were reported over 12 months. Introducing NIKBUT as part of routine CL fitting is advised to improve CL fit and predict success.
Distinct aberrations in cerebral pain processing differentiating patients with fibromyalgia from patients with rheumatoid arthritis
Authors: Sandström Angelica , Ellerbrock Isabel , Löfgren Monika , Altawil Reem , Bileviciute-Ljungar Indre , Lampa Jon , Kosek Eva 
Published: July 2021

Abstract
The current study used functional magnetic resonance imaging to directly compare disease-relevant cerebral pain processing in well-characterized patient cohorts of fibromyalgia (FM, nociplastic pain) and rheumatoid arthritis (RA, nociceptive pain). Secondary aims were to identify pain-related cerebral alterations related to the severity of clinical symptoms such as pain intensity, depression, and anxiety. Twenty-six patients with FM (without RA-comorbidity) and 31 patients with RA (without FM-comorbidity) underwent functional magnetic resonance imaging while stimulated with subjectively calibrated painful pressures corresponding to a pain sensation of 50 mm on a 100-mm visual analogue scale. Stimulation sites were at the most inflamed proximal interphalangeal joint in the left hand in patients with RA and the left thumbnail in patients with FM, 2 sites that have previously been shown to yield the same brain activation in healthy controls. The current results revealed disease-distinct differences during pain modulation in RA and FM. Specifically, in response to painful stimulation, patients with FM compared to patients with RA exhibited increased brain activation in bilateral inferior parietal lobe (IPL), left inferior frontal gyrus (IFG)/ventrolateral prefrontal cortex (vlPFC) encapsulating left dorsolateral prefrontal cortex, and right IFG/vlPFC. However, patients with RA compared to patients with FM exhibited increased functional connectivity (during painful stimulation) between right and left IPL and sensorimotor network and between left IPL and frontoparietal network. Within the FM group only, anxiety scores positively correlated with pain-related brain activation in left dorsolateral prefrontal cortex and right IFG/vlPFC, which further highlights the complex interaction between affective (ie, anxiety scores) and sensory (ie, cerebral pain processing) dimensions in this patient group.