bluuebunny/crossref_metadata_2025_split huggingface dataset:
Serine-Glycine-One-Carbon Metabolism: The Hidden Achilles Heel of MYCN-Amplified Neuroblastoma?
Authors: Garcia Aida Rodriguez , Arsenian-Henriksson Marie 
Published: August 2019

Abstract
In this issue of Cancer Research, Xia and colleagues show that MYC-induced metabolic reprograming results in dependency on the serine-glycine-one-carbon (SGOC) metabolic pathway in neuroblastoma. This occurs through MYCN and ATF4 activation of the SGOC biosynthetic pathway in MYCN-amplified cells. Furthermore, inhibition of de novo serine synthesis generates metabolic stress in MYCN-amplified neuroblastoma cells, causing cell-cycle arrest and autophagy. Together, these data suggest that the SGOC pathway is an attractive therapy target in neuroblastoma.
See related article by Xia et al., p. 3837
Anti-OX40 Antibody Directly Enhances The Function of Tumor-Reactive CD8+ T Cells and Synergizes with PI3Kβ Inhibition in PTEN Loss Melanoma
Authors: Peng Weiyi , Williams Leila J. , Xu Chunyu , Melendez Brenda , McKenzie Jodi A. , Chen Yuan , Jackson Heather L. , Voo Kui S. , Mbofung Rina M. , Leahey Sara Elizabeth , Wang Jian , Lizee Gregory , Tawbi Hussein A. , Davies Michael A. , Hoos Axel , Smothers James , Srinivasan Roopa , Paul Elaine M. , Yanamandra Niranjan , Hwu Patrick 
Published: August 2019

Abstract

Purpose:
OX40 agonist–based combinations are emerging as a novel avenue to improve the effectiveness of cancer immunotherapy. To better guide its clinical development, we characterized the role of the OX40 pathway in tumor-reactive immune cells. We also evaluated combining OX40 agonists with targeted therapy to combat resistance to cancer immunotherapy.
Experimental Design: We utilized patient-derived tumor-infiltrating lymphocytes (TILs) and multiple preclinical models to determine the direct effect of anti-OX40 agonistic antibodies on tumor-reactive CD8+ T cells. We also evaluated the antitumor activity of an anti-OX40 antibody plus PI3Kβ inhibition in a transgenic murine melanoma model (Braf mutant, PTEN null), which spontaneously develops immunotherapy-resistant melanomas.

Results:
We observed elevated expression of OX40 in tumor-reactive CD8+ TILs upon encountering tumors; activation of OX40 signaling enhanced their cytotoxic function. OX40 agonist antibody improved the antitumor activity of CD8+ T cells and the generation of tumor-specific T-cell memory in vivo. Furthermore, combining anti-OX40 with GSK2636771, a PI3Kβ-selective inhibitor, delayed tumor growth and extended the survival of mice with PTEN-null melanomas. This combination treatment did not increase the number of TILs, but it instead significantly enhanced proliferation of CD8+ TILs and elevated the serum levels of CCL4, CXCL10, and IFNγ, which are mainly produced by memory and/or effector T cells.

Conclusions:
These results highlight a critical role of OX40 activation in potentiating the effector function of tumor-reactive CD8+ T cells and suggest further evaluation of OX40 agonist–based combinations in patients with immune-resistant tumors.
Ly6C
+
Inflammatory Monocyte Differentiation Partially Mediates Hyperhomocysteinemia-Induced Vascular Dysfunction in Type 2 Diabetic db/db Mice
Authors: Fang Pu , Li Xinyuan , Shan Huimin , Saredy Jason J. , Cueto Ramon , Xia Jixiang , Jiang Xiaohua , Yang Xiao-Feng , Wang Hong 
Published: August 2019

Objective:
Hyperhomocysteinemia (HHcy) is a potent risk factor for diabetic cardiovascular diseases. We have previously reported that hyperhomocysteinemia potentiates type 1 diabetes mellitus-induced inflammatory monocyte differentiation, vascular dysfunction, and atherosclerosis. However, the effects of hyperhomocysteinemia on vascular inflammation in type 2 diabetes mellitus (T2DM) and the underlying mechanism are unknown.

Approach and Results:

Here, we demonstrate that hyperhomocysteinemia was induced by a high methionine diet in control mice (homocysteine 129 µmol/L), which was further worsened in T2DM db/db mice (homocysteine 180 µmol/L) with aggravated insulin intolerance. Hyperhomocysteinemia potentiated T2DM-induced mononuclear cell, monocyte, inflammatory monocyte (CD11b
+
Ly6C
+
), and M1 macrophage differentiation in periphery and aorta, which were rescued by folic acid-based homocysteine-lowering therapy. Moreover, hyperhomocysteinemia exacerbated T2DM-impaired endothelial-dependent aortic relaxation to acetylcholine. Finally, transfusion of bone marrow cells depleted for Ly6C by
Ly6c
shRNA transduction improved insulin intolerance and endothelial-dependent aortic relaxation in hyperhomocysteinemia+T2DM mice.

Conclusions:
Hyperhomocysteinemia potentiated systemic and vessel wall inflammation and vascular dysfunction partially via inflammatory monocyte subset induction in T2DM. Inflammatory monocyte may be a novel therapeutic target for insulin resistance, inflammation, and cardiovascular complications in hyperhomocysteinemia+T2DM.
Effects of Hormone Therapy on Heart Fat and Coronary Artery Calcification Progression: Secondary Analysis From the KEEPS Trial
Authors: El Khoudary Samar R. , Zhao Qian , Venugopal Vidya , Manson JoAnn E. , Brooks Maria M. , Santoro Nanette , Black Dennis M. , Harman S. Mitchell , Cedars Marcelle I. , Hopkins Paul N. , Kearns Ann E. , Miller Virginia M. , Taylor Hugh S. , Budoff Matthew J. 
Published: August 2019

Background

Heart fats (epicardial and paracardial adipose tissue [PAT]) are greater after menopause. Endogenous estrogen may regulate these fat depots. We evaluated the differential effects of hormone therapy formulations on heart fat accumulations and their associations with coronary artery calcification (
CAC
) progression in recently menopausal women from KEEPS (Kronos Early Estrogen Prevention Study).

Methods and Results

KEEPS
was a multicenter, randomized, placebo‐controlled trial of the effects of 0.45 mg/d oral conjugated equine estrogens and 50 µg/d transdermal 17β‐estradiol, compared with placebo, on 48‐month progression of subclinical atherosclerosis among 727 early menopausal women.
CAC
progression was defined if baseline
CAC
score was 0 and 48‐month
CAC
score was >0 or if baseline
CAC
score was >0 and <100 and annualized change in
CAC
score was ≥10. Of 727
KEEPS
participants, 474 (mean age: 52.7 [SD: 2.6]; 78.1% white) had computed tomography–based heart fat and
CAC
measures at both baseline and 48 months. Compared with women on placebo, women on oral conjugated equine estrogens were less likely to have any increase in epicardial adipose tissue (odds ratio for oral conjugated equine estrogens versus placebo: 0.62 [95% CI, 0.40–0.97];
P
=0.03).
PAT
did not change in any group. Changes in epicardial adipose tissue and
PAT
did not differ by treatment group.
CAC
increased in 14% of participants. The assigned treatment modified the association between
PAT
changes and
CAC
progression (
P
=0.02) such that
PAT
increases were associated with
CAC
increases only in the transdermal 17β‐estradiol group.

Conclusions

In recently menopausal women, oral conjugated equine estrogens may slow epicardial adipose tissue accumulation, whereas transdermal 17β‐estradiol may increase progression of
CAC
associated with
PAT
accumulation.

Clinical Trial Registration

URL
:
http://www.clinicaltrials.gov
. Unique identifier:
NCT
00154180.
How College Credit in High School Impacts Postsecondary
Course-Taking: The Role of Advanced Placement Exams
Authors: Gurantz Oded 
Published: August 2019

Abstract
This paper uses Advanced Placement (AP) exams to examine how receiving college credit in high school alters students’ subsequent human capital investment. Using data from one large state, I link high school students to postsecondary transcripts from in-state, public institutions. I estimate causal impacts using a regression discontinuity that compares students with essentially identical AP performance but who receive different offers of college credit. I find that female students who earn credit from science, technology, engineering, and mathematics (STEM) exams take higher level STEM courses, significantly increasing their depth of study, with no observed impacts for male students. As a result, the male–female gap in STEM courses taken shrinks by roughly one third to two thirds, depending on the outcome studied. Earning non-STEM AP credit increases overall coursework in non-STEM courses and increases the breadth of study across departments. Early credit policies help assist colleges to produce graduates whose skills aligns with commonly cited social or economic priorities, such as developing STEM graduates with stronger skills, particularly among traditionally underrepresented groups.
On a collection of caridean shrimps (Decapoda, Caridea) from St. Helena, south-central Atlantic, with further records from Ascension Island
Authors: De Grave Sammy , Brown Judith , Wirtz Peter , Anker Arthur 
Published: August 2019

Abstract
We report on a recent collection of caridean shrimps from St. Helena in the south-central Atlantic Ocean, raising the total number of species known from the island to 24. Six species are newly recorded for the area, with no endemic species present. Additional three species are recorded from Ascension Island. A close biogeographical connection between the caridean faunas of St. Helena and Ascension Island is evident.
Blast-Induced Cholesteatomas After Spontaneous Tympanic Membrane Healing
Authors: Ungar Omer J. , Shilo Shahaf , Anat Wengier , Cavel Oren , Handzel Ophir , Oron Yahav 
Published: August 2019

Objectives: To characterize blast-induced cholesteatomas (BIC) in terms of symptoms, presentation, and location within the middle ear cleft (MEC). Design: A search for all English language articles in “MEDLINE” via “PubMed” and “Google Scholar” was conducted. Results: A total of 67 ears with BIC were included. Fifty-eight ears in which the traumatic perforation failed to spontaneously close were excluded, leaving seven case reports (eight patients, nine ears) for statistical analysis. Time between blast exposure to spontaneous tympanic membrane (TM) closure was 16 days to 10 months. Time between blast exposure and cholesteatoma diagnosis was 5 months to 4 years. The cholesteatomas were diagnosed due to symptoms in two ears, as asymptomatic finding on physical examination in one ear and as asymptomatic finding in axial imaging in three ears. Conclusions: BICs can develop behind intact tympanic membrane or along with TM perforation. Based on the current review, when a TM perforation and spontaneous healing were documented, after blast exposure, MRI scan is an integral component of the follow-up. The optimal timing for MRI performance after blast exposure, is yet to be identified.
What influences patients’ decisions regarding palliative care in advance care planning discussions? Perspectives from a qualitative study conducted with advanced cancer patients, families and healthcare professionals
Authors: Lin Cheng-Pei , Evans Catherine J , Koffman Jonathan , Sheu Shuh-Jen , Hsu Su-Hsuan , Harding Richard 
Published: August 2019

Background: The concept of advance care planning is largely derived from Western countries. However, the decision-making process and drivers for choosing palliative care in non-Western cultures have received little attention. Aim: To explore the decision-making processes and drivers of receiving palliative care in advance care planning discussions from perspectives of advanced cancer patients, families and healthcare professionals in northern Taiwan. Method: Semi-structured qualitative interviews with advanced cancer patients, their families and healthcare professionals independently from inpatient oncology and hospice units. Thematic analysis with analytical rigour enhanced by dual coding and exploration of divergent views. Results: Forty-five participants were interviewed ( n = 15 from each group). Three main decision-making trajectories were identified: (1) ‘choose palliative care’ was associated with patients’ desire to reduce physical suffering from treatments, avoid being a burden to families and society, reduce futile treatments and donate organs to help others; (2) ‘decline palliative care’ was associated with patients weighing up perceived benefits to others as more important than benefits for themselves; and (3) ‘no opportunity to choose palliative care’ was associated with lack of opportunities to discuss potential benefits of palliative care, lack of staff skill in end-of-life communication, and cultural factors, notably filial piety. Conclusion: Choice for palliative care among advanced cancer patients in Taiwan is influenced by three decision-making trajectories. Opinions from families are highly influential, and patients often lack information on palliative care options. Strategies to facilitate decision-making require staff confidence in end-of-life discussions, working with the patients and their family while respecting the influence of filial piety.
The use of personal narratives in hospital-based palliative care interventions: An integrative literature review
Authors: Roikjær Stine Gundtoft , Missel Malene , Bergenholtz Heidi Maria , Schønau Mai Nanna , Timm Helle Ussing 
Published: August 2019

Background: People living with life-threatening illness experience unmet existential needs despite the growing research and clinical field of palliative care. Narrative interventions show promise in managing these problems, but more knowledge is needed on the characteristics of narrative interventions and the feasibility of using personal narratives in a hospital. Aim: To review the literature on personal narratives in hospital-based palliative care interventions and to strengthen palliative care practices. Design: We conducted a systematic integrative review with qualitative analysis and narrative synthesis in accordance with PRISMA where applicable (PROSPERO#:CRD42018089202). Data sources: We conducted a systematic search in PubMed, Embase, Scopus, Cinahl, SocINDEX and PsychInfo for primary research articles published until June 2018. We assessed full-text articles against the eligibility criteria followed by a discussion of quality using the Critical Appraisal Skills Programme. Results: Of 480 articles, we found 24 eligible for this review: 8 qualitative, 14 quantitative and 2 mixed methods. The articles reported on dignity therapy, legacy building, outlook, short-term life review and life review. Data analysis resulted in five themes: core principles, theoretical framework, content of narrative, outcome and, finally, acceptability and feasibility. Conclusion: Various types of systematic palliative care interventions use personal narratives. Common to these is a shared psychotherapeutic theoretical understanding and aim. Clinical application in a hospital setting is both feasible and acceptable but requires flexibility regarding the practices of the setting and the needs of the patient.
Family sense of coherence and its associations with hope, anxiety and symptoms of depression in persons with cancer in palliative phase and their family members: A cross-sectional study
Authors: Möllerberg Marie-Louise , Årestedt Kristofer , Swahnberg Katarina , Benzein Eva , Sandgren Anna 
Published: August 2019

Background: There is evidence indicating that family sense of coherence predicts quality of family life and promotes family well-being. In families living with the palliative phase of cancer, low hope, anxiety and symptoms of depression are common in both persons with cancer and their family members. Aim: To determine whether family sense of coherence was associated with hope, anxiety and symptoms of depression, respectively, in persons with cancer in the palliative phase and their family members. Design: An observational, cross-sectional, multicentre study was conducted. Nested linear regression analyses were performed in two blocks to determine whether family sense of coherence was associated with hope, anxiety and symptoms of depression. Setting/participants: Persons with cancer ( n = 179) and their family members ( n = 165) were recruited from two oncology clinics and two palliative centres in three regions in Sweden. Results: The main findings showed that family sense of coherence was significantly and independently associated with hope, anxiety and symptoms of depression. Stronger family sense of coherence was associated with higher hope and lower anxiety and symptoms of depression levels in both persons with cancer and their family members. Conclusion: Health care providers should strive to identify families with weak family sense of coherence, because of its associations with hope, anxiety and symptoms of depression, in order to offer them professional support and thereby achieve increased well-being during the palliative phase of cancer. Future studies should expand our knowledge of family sense of coherence and how to identify families at risk of lower levels of well-being.
Effect of articular capsule repair on postoperative dislocation after primary total hip replacement by the anterolateral approach
Authors: Lu Yiran , Wu Zongming , Tang Xianzhong , Gu Mengzhen , Hou Bo 
Published: August 2019

Objective Artificial hip dislocation is one of the most serious complications following total hip replacement. This study was performed to assess articular capsule repair in primary total hip replacement with the anterolateral approach (Watson-Jones incision) and its effect on postoperative dislocation. Methods Patients who underwent primary total hip replacement by the anterolateral approach in Tongren Hospital of Shanghai Jiao Tong University School of Medicine from June 2007 to June 2014 were retrospectively analyzed. The patients were divided into the repair and dissection groups based on the articular capsule repair status during surgery. Postoperative dislocation rates were compared between the two groups using the chi-squared test. Results The repair and dissection groups comprised 137 and 248 patients, respectively. All patients were followed up for 6 months to 5 years (average, 3.75 years). The mean age, sex, disease composition, and follow-up time were not significantly different between the two groups. Early postoperative dislocation occurred in 1 hip (0.7%) in the repair group and 13 hips (5.2%) in the dissection group. Conclusions During the anterolateral approach for primary total hip replacement, articular capsule repair may reduce the occurrence of early postoperative dislocation of the hip joint.
Relationship of Velopharyngeal Insufficiency With Face Mask Therapy in Patients With Cleft Lip and Palate
Authors: Helal Narmin , Ford Matthew , Basri Osama , Schuster Lindsay , Martin Brian , Losee Joseph 
Published: August 2019

Objective: To determine whether orthodontic/dentofacial orthopedic maxillary protraction face mask therapy induces changes in velopharyngeal functioning in a cohort of pediatric patients having cleft palate with or without cleft lip. Design: Retrospective chart review. Setting: A children’s hospital in the United States. Participants: Forty-three pediatric patients with cleft palate, with or without cleft lip, syndromic or with isolated clefts, who received face mask therapy from January 2009 to April 2016. Intervention: Clinical data were extracted for review and analysis from medical records obtained from the Cleft Database/Research Registry (CDB-RR). Main Outcome Measures: Pittsburgh Weighted Speech Scores (PWSS) before and after therapy. Results: There was a significant increase in PWSS after face mask therapy for patients with a PWSS score of 0 prior to treatment. Patients with PWSS >0 before treatment remained largely stable after face mask therapy. Maxillary advancement was not significantly associated with change in PWSS or fistula presence/absence. Conclusions: There is an increased risk of velopharyngeal insufficiency with maxillary protraction face mask treatment in patients with cleft palate. Patient counseling and obtaining consent regarding speech changes during treatment are recommended.
The genetic diversity of multiple sclerosis risk among Hispanic and African American populations living in the United States
Authors: Beecham AH , Amezcua L , Chinea A , Manrique CP , Rubi C , Isobe N , Lund BT , Santaniello A , Beecham GW , Burchard EG , Comabella M , Patsopoulos N , Fitzgerald K , Calabresi PA , De Jager P , Conti DV , Delgado SR , Oksenberg JR , McCauley JL 
Published: August 2019

Background: Substantial progress has been made toward unraveling the genetic architecture of multiple sclerosis (MS) within populations of European ancestry, but few genetic studies have focused on Hispanic and African American populations within the United States. Objective: We sought to test the relevance of common European MS risk variants outside of the major histocompatibility complex ( n = 200) within these populations. Methods: Genotype data were available on 2652 Hispanics (1298 with MS, 1354 controls) and 2435 African Americans (1298 with MS, 1137 controls). We conducted single variant, pathway, and cumulative genetic risk score analyses. Results: We found less replication than statistical power suggested, particularly among African Americans. This could be due to limited correlation between the tested and causal variants within the sample or alternatively could indicate allelic and locus heterogeneity. Differences were observed between pathways enriched among the replicating versus all 200 variants. Although these differences should be examined in larger samples, a potential role exists for gene–environment or gene–gene interactions which alter phenotype differentially across racial and ethnic groups. Cumulative genetic risk scores were associated with MS within each study sample but showed limited diagnostic capability. Conclusion: These findings provide a framework for fine-mapping efforts in multi-ethnic populations of MS.
Current evidence for vitamin D in intestinal function and disease
Authors: Hassanshahi Mohammadhossein , Anderson Paul H , Sylvester Cyan L , Stringer Andrea M 
Published: August 2019

Vitamin D activity is associated with the modulation of a wide variety of biological systems, in addition to its roles in calcium homeostatic mechanisms. While vitamin D is well known to promote gastrointestinal calcium absorption, vitamin D also plays a role in attenuating and/or preventing the progression of several gastrointestinal diseases including Crohn’s disease, ulcerative colitis, and colorectal cancer, and may also play a role in chemotherapy-induced intestinal mucositis. The pro-differentiation, immunomodulatory, and anti-inflammatory effects of vitamin D, which has been reported in numerous circumstances, are key potential mechanisms of action in the prevention of gastrointestinal disorders. While the debate of the effectiveness of vitamin D to treat bone pathologies continues, the clinical importance of vitamin D therapy to prevent gastrointestinal disorders should be investigated given current evidence, using both nutritional and pharmaceutical intervention approaches.Impact statementThe non-skeletal functions of vitamin D play an important role in health and disease. The anti-inflammatory properties and maintenance of intestinal function fulfilled by vitamin D impact other systems in the body though downstream processing. This review provides insight into the mechanisms underpinning the potential benefits of vitamin D in both maintaining intestinal homeostasis and associated diseased states.