bluuebunny/crossref_metadata_2025_split huggingface dataset:
MGMT promoter methylation level in newly diagnosed low-grade glioma is a predictor of hypermutation at recurrence
Authors: Mathur Radhika , Zhang Yalan , Grimmer Matthew R , Hong Chibo , Zhang Michael , Bollam Saumya , Petrecca Kevin , Clarke Jennifer , Berger Mitchel S , Phillips Joanna J , Oberheim-Bush Nancy Ann , Molinaro Annette M , Chang Susan M , Costello Joseph F 
Published: March 2020

Abstract

Background
Emerging data suggest that a subset of patients with diffuse isocitrate dehydrogenase (IDH)-mutant low-grade glioma (LGG) who receive adjuvant temozolomide (TMZ) recur with hypermutation in association with malignant progression to higher-grade tumors. It is currently unclear why some TMZ-treated LGG patients recur with hypermutation while others do not. MGMT encodes O6-methylguanine-DNA methyltransferase, a DNA repair protein that removes cytotoxic and potentially mutagenic lesions induced by TMZ. Here, we hypothesize that epigenetic silencing of MGMT by promoter methylation facilitates TMZ-induced mutagenesis in LGG patients and contributes to development of hypermutation at recurrence.

Methods
We utilize a quantitative deep sequencing assay to characterize MGMT promoter methylation in 109 surgical tissue specimens from initial tumors and post-treatment recurrences of 37 TMZ-treated LGG patients. We utilize methylation arrays to validate our sequencing assay, RNA sequencing to assess the relationship between methylation and gene expression, and exome sequencing to determine hypermutation status.

Results
Methylation level at the MGMT promoter is significantly higher in initial tumors of patients that develop hypermutation at recurrence relative to initial tumors of patients that do not (45.7% vs 34.8%, P = 0.027). Methylation level in initial tumors can predict hypermutation at recurrence in univariate models and multivariate models that incorporate patient age and molecular subtype.

Conclusions
These findings reveal a mechanistic basis for observed differences in patient susceptibility to TMZ-driven hypermutation. Furthermore, they establish MGMT promoter methylation level as a potential biomarker to inform clinical management of LGG patients, including monitoring and treatment decisions, by predicting risk of hypermutation at recurrence.
A Bayesian adaptive randomized phase II multicenter trial of bevacizumab with or without vorinostat in adults with recurrent glioblastoma
Authors: Puduvalli Vinay K , Wu Jing , Yuan Ying , Armstrong Terri S , Vera Elizabeth , Wu Jimin , Xu Jihong , Giglio Pierre , Colman Howard , Walbert Tobias , Raizer Jeffrey , Groves Morris D , Tran David , Iwamoto Fabio , Avgeropoulos Nicholas , Paleologos Nina , Fink Karen , Peereboom David , Chamberlain Marc , Merrell Ryan , Penas Prado Marta , Yung W K Alfred , Gilbert Mark R 
Published: March 2020

AbstractBackgroundBevacizumab has promising activity against recurrent glioblastoma (GBM). However, acquired resistance to this agent results in tumor recurrence. We hypothesized that vorinostat, a histone deacetylase (HDAC) inhibitor with anti-angiogenic effects, would prevent acquired resistance to bevacizumab.MethodsThis multicenter phase II trial used a Bayesian adaptive design to randomize patients with recurrent GBM to bevacizumab alone or bevacizumab plus vorinostat with the primary endpoint of progression-free survival (PFS) and secondary endpoints of overall survival (OS) and clinical outcomes assessment (MD Anderson Symptom Inventory Brain Tumor module [MDASI-BT]). Eligible patients were adults (≥18 y) with histologically confirmed GBM recurrent after prior radiation therapy, with adequate organ function, KPS ≥60, and no prior bevacizumab or HDAC inhibitors.ResultsNinety patients (bevacizumab + vorinostat: 49, bevacizumab: 41) were enrolled, of whom 74 were evaluable for PFS (bevacizumab + vorinostat: 44, bevacizumab: 30). Median PFS (3.7 vs 3.9 mo, P = 0.94, hazard ratio [HR] 0.63 [95% CI: 0.38, 1.06, P = 0.08]), median OS (7.8 vs 9.3 mo, P = 0.64, HR 0.93 [95% CI: 0.5, 1.6, P = 0.79]) and clinical benefit were similar between the 2 arms. Toxicity (grade ≥3) in 85 evaluable patients included hypertension (n = 37), neurological changes (n = 2), anorexia (n = 2), infections (n = 9), wound dehiscence (n = 2), deep vein thrombosis/pulmonary embolism (n = 2), and colonic perforation (n = 1).ConclusionsBevacizumab combined with vorinostat did not yield improvement in PFS or OS or clinical benefit compared with bevacizumab alone or a clinical benefit in adults with recurrent GBM. This trial is the first to test a Bayesian adaptive design with adaptive randomization and Bayesian continuous monitoring in patients with primary brain tumor and demonstrates the feasibility of using complex Bayesian adaptive design in a multicenter setting.
Associations of maternal stress and/or depressive symptoms with diet quality during pregnancy: a narrative review
Authors: Boutté Alycia K , Turner-McGrievy Gabrielle M , Wilcox Sara , Liu Jihong , Eberth Jan M , Kaczynski Andrew T 
Published: March 2020

AbstractBackgroundPregnancy can be a stressful time for many women; however, it is unclear if higher stress and depressive symptoms are associated with poorer diet quality during pregnancy.ObjectiveThe aims for this narrative review were to (1) synthesize findings of original, peer-reviewed studies that examined associations of stress and/or depressive symptoms with diet quality during pregnancy; (2) review the measurement tools used to assess stress, depressive symptoms, and diet quality; (3) identify current gaps in the extant literature; and (4) offer recommendations for future research.MethodsA search strategy was used to identify peer-reviewed manuscripts published between January 1997 and October 2018, using the following databases: PubMed, CINAHL Complete, PsycINFO, Academic Search Complete, and Psychology & Behavioral Sciences Collection. The search was updated December 2019. Two reviewers independently assessed title, abstract, and full-text of the studies that met the inclusion criteria. Data were extracted and a quality assessment was conducted.ResultsTwenty-seven observational studies were identified in this review (21 cross-sectional and 6 longitudinal). In 22 studies, higher stress and/or depressive symptoms were associated with poorer diet quality or unhealthy dietary patterns; 5 studies found no association. Findings are mixed and inconclusive regarding the relationship among stress, depressive symptoms, and food groups related to diet quality and frequency of fast-food consumption.ConclusionsThe current data suggest stress and depressive symptoms may be a barrier to proper diet quality during pregnancy; however, variability in the assessment tools, timing of assessments, and use of covariates likely contribute to the inconsistency in study findings. Gaps in the literature include limited use of longitudinal study designs, limited use of comprehensive diet-quality indices, underrepresentation of minority women, and lack of multilevel theoretical frameworks. Studies should address these factors to better assess associations of stress and/or depressive symptoms with diet quality during pregnancy.
J. Laurence Laughlin versus Irving Fisher on the quantity theory of money, 1894 to 1913
Authors: Dimand Robert W 
Published: March 2020

AbstractIn the controversy leading to the Federal Reserve Act of 1913, J. Laurence Laughlin of the University of Chicago and Irving Fisher of Yale were the leading opponent and proponent, respectively, of the quantity theory of money as the theoretical basis for reorganizing the US monetary system. Laughlin identified the quantity theory with bimetallist claims that monetizing silver would have lasting real benefits. Laughlin offered a cost of production theory of the value of gold as an alternative to the quantity theory, while his students published empirical critiques of the quantity theory. Fisher upheld the quantity theory as explaining price movements while distancing the theory from assertions of long-run non-neutrality of money. Laughlin and Fisher vigorously debated monetary theory and monetary reform, notably at American Economic Association meetings. Their confrontations illuminate the monetary controversies preceding the Federal Reserve Act, which reflected the views of Laughlin and Willis (adviser to Congressman Carter Glass) while rejecting the mandate to stabilize the price level proposed by Senator Owen and his adviser Fisher.
Clinical practice guidelines and recommendations for the management of patients with systemic lupus erythematosus: a critical comparison
Authors: Oliveira Margarida , Palacios-Fernandez Sergio , Cervera Ricard , Espinosa Gerard 
Published: March 2020

Abstract

Objective
SLE has a great clinical heterogeneity and low prevalence, thus making the development of recommendations or clinical practice guidelines (CPG) based on high-quality evidence difficult. In the last few years, several CPG appeared addressing the management of the disease. The aim of this review is to critically compare the recommendations made in the most recent CPG and to analyse and compare their methodological quality.

Methods
The Appraisal of Guidelines for Research and Evaluation (AGREE) II tool was used to compare the methodological quality of each of the CPG.

Results
Most CPG agreed in the general management and first-line treatment recommendations where there is higher quality evidence and disagreed in refractory disease treatment where there is lack of quality evidence. Also, the CPG are agreed in whether a patient should be treated regarding the most severe clinical manifestation or taking into account the treatment that best serves all clinical manifestations. The majority of the appraised CPG scored high-quality ratings, especially for scope and purpose and clarity of presentation, while they were of less quality when assessing applicability of each CPG.

Conclusion
CPG should aid, but not replace, the health professional’s clinical judgment in daily clinical patient management.
Therapeutic targeting of the DNA damage response in prostate cancer
Authors: Marshall Catherine H. , Antonarakis Emmanuel S. 
Published: March 2020

Purpose of reviewThe present article highlights the most common DNA repair gene mutations, using specific examples of individual genes or gene classes, and reviews the epidemiology and treatment implications for each one [with particular emphasis on poly-ADP-ribose polymerase (PARP) inhibition and PD-1 blockade].Recent findingsGenetic and genomic testing have an increasingly important role in the oncology clinic. For patients with prostate cancer, germline genetic testing is now recommended for all men with high-risk and metastatic disease, and somatic multigene tumor testing is recommended for men with metastatic castration-resistant disease. The most common mutations that are present in men with advanced prostate cancer are in genes coordinating DNA repair and the DNA damage response.SummaryAlthough much of what is discussed currently remains investigational, it is clear that genomically-targeted treatments will become increasingly important for patients with prostate cancer in the near future and beyond.
Pelvic floor disorders in women with premature ovarian insufficiency: a cross-sectional study
Authors: Fante Júlia Ferreira , Machado Helymar da Costa , Juliato Cassia Raquel Teatin , Benetti-Pinto Cristina Laguna , Brito Luiz Gustavo Oliveira 
Published: March 2020

Abstract

Objectives:
This study aimed to investigate the prevalence of self-reported main pelvic floor disorders (PFD) (urinary incontinence [UI], pelvic organ prolapse [POP], and fecal incontinence [FI]) and its associated factors in women with premature ovarian insufficiency (POI) and a control group.

Methods:
This was a cross-sectional study wherein two groups were interviewed from August, 2017 to November, 2018—women with POI (n = 150) and a control group matched for age and body weight (n = 150). Sociodemographic variables and two questionnaires validated in Brazilian Portuguese language for PFD (Kings Health Questionnaire [KHQ] and Pelvic Floor Distress Inventory—20 [PFDI-20]) were used. Laycock's power, endurance, repetitions, fast contractions, every contraction timed (PERFECT) scale for pelvic floor muscle assessment was used in both groups.

Results:
The prevalence of self-reported UI was 27.33% and 37.33% for POI and control groups (P > 0.05), respectively. There was no perceived difference regarding the prevalence of POP (9.33% POI group vs 8% control group; P = 0.682) and FI (8% POI vs 4% control group; P = 0.145). The P (power) (P = 0.46), E (endurance) (P = 0.91), R (repetitions) (P = 0.88), and F (fast contractions) (P = 0.19) values were statistically similar in both the groups. Multivariate analysis (n = 141) showed that higher weight (odds ratio [OR] 1.047 [1.018-1.076]; P < 0.001) and gravidity rates (OR 1.627 [1.169-2.266]; P < 0.01) were risk factors for UI and higher weight (OR 1.046 [1.010-1.084]; P = 0.01), and presence of comorbidities (OR 8.75 [1.07-71.44]; P < 0.01) were risk factors for POP in the POI group; there was no variable that was associated with FI.

Conclusions:
Women with POI did not have significant differences when compared with the control group regarding the prevalence of PFD and pelvic floor muscle assessment. Having higher weight and gravidity rates were associated with self-reported UI, while the presence of comorbidities and higher weight were risk factors for POP in the POI group.

Video Summary:
http://links.lww.com/MENO/A555.
The many flavors of monocyte/macrophage--endothelial cell interactions
Authors: Hernandez Gloria E. , Iruela-Arispe M. Luisa 
Published: March 2020

Purpose of review
The well recognized plasticity and diversity, typical of monocytes and macrophages have recently been expanded by the knowledge that additional macrophage lineages originated directly from embryonic progenitors, populate and establish residency in all tissues examined so far. This review aims to summarize our current understanding on the diversity of monocyte/macrophage subtypes associated with the vasculature, their specific origins, and nature of their cross-talk with the endothelium.

Recent findings
Taking stock of the many interactions between the endothelium and monocytes/macrophages reveals a far more intricate and ever-growing depth. In addition to circulating and surveilling the endothelium, monocytes can specifically be differentiated into patrolling cells that crawl on the surface of the endothelium and promote homeostasis. The conversion of classical to patrolling is endothelium-dependent uncovering an important functional link. In addition to patrolling cells, the endothelium also recruits and harbor an intimal-resident myeloid population that resides in the tunica intima in the absence of pathological insults. Moreover, the adventitia is populated with resident macrophages that support blood vessel integrity and prevent fibrosis.

Summary
The last few years have witnessed a significant expansion in our knowledge of the many subtypes of monocytes and macrophages and their corresponding functional interactions with the vascular wall. In addition to surveying the endothelium for opportunities of diapedeses, monocyte and macrophages take residence in both the intima (as patrolling or resident) and in the adventitia. Their contributions to vascular function are broad and critical to homeostasis, regeneration, and expansion.
Small molecule therapeutics to treat the β-globinopathies
Authors: Yu Lei , Myers Greggory , Engel James D. 
Published: March 2020

Purpose of reviewThe current review focuses on recent insights into the development of small molecule therapeutics to treat the β-globinopathies.Recent findingsRecent studies of fetal γ-globin gene regulation reveal multiple insights into how γ-globin gene reactivation may lead to novel treatment for β-globinopathies.SummaryWe summarize current information regarding the binding of transcription factors that appear to be impeded or augmented by different hereditary persistence of fetal hemoglobin (HPFH) mutations. As transcription factors have historically proven to be difficult to target for therapeutic purposes, we next address the contributions of protein complexes associated with these HPFH mutation-affected transcription factors with the aim of defining proteins that might provide additional targets for chemical molecules to inactivate the corepressors. Among the enzymes associated with the transcription factor complexes, a group of corepressors with currently available inhibitors were initially thought to be good candidates for potential therapeutic purposes. We discuss possibilities for pharmacological inhibition of these corepressor enzymes that might significantly reactivate fetal γ-globin gene expression. Finally, we summarize the current clinical trial data regarding the inhibition of select corepressor proteins for the treatment of sickle cell disease and β-thalassemia.
Reasons for worldwide decline in male fertility
Authors: Mann Uday , Shiff Benjamin , Patel Premal 
Published: March 2020

Purpose of review
To review the evidence regarding a decrease in worldwide sperm parameters and discuss potential causative factors.

Recent findings
The topic of worldwide decline in sperm parameters is contentious; however, recent high-quality studies have demonstrated that there is indeed a decline in sperm parameters. Several retrospective and basic science studies have shown possible links for this decline in sperm parameters such as obesity, diet, and environmental toxins.

Summary
There exist substantial data to suggest a decline in sperm counts over time. Although causative factors have yet to be fully elucidated, potential causes include, increased rates of obesity, poor diet, and exposure to environmental toxins. How this decline in sperm counts reflects fertility has yet to be determined. As such, further studies are necessary to evaluate whether this decline in sperm count correlates with decreased fecundity and how to identify and mitigate potential causative factors.
Desmoplasia and Biophysics in Pancreatic Ductal Adenocarcinoma
Authors: Di Maggio Francesco , El-Shakankery Karim Hussien 
Published: March 2020

Abstract
Pancreatic ductal adenocarcinoma (PDAC) treatments have historically focused on targeting tumor cells directly. However, in pancreatic masses, the stroma encasing the malignant epithelial cells constitutes up to 80% to 90% of the tumor bulk. This extracellular matrix, which was previously neglected when designing cancer therapies, is now considered fundamental for tumor progression and drug delivery. Desmoplastic tissue is extensively cross-linked, resulting in tremendous tensile strength. This key pathological feature is procarcinogenic, linking PDAC and breast cancer (BC). Physical forces exerted onto cellular surfaces are detected intracellularly and transduced via biochemical messengers in a process called mechanotransduction. Mechanotransduction and tensional homeostasis are linked, with an integral role in influencing tumor growth, metastasis, and interactions with the immune system. It is essential to enhance our knowledge of these integral elements of parenchymal tumors. We aim to review the topic, with a special emphasis on desmoplastic processes and their importance in pancreatic and BC development and treatments, mindful that innovative diagnostic and therapeutic strategies cannot focus on biochemical pathways alone. We then focus on common therapeutic targets identified in both PDAC and BC models and/or patients, aiming to understand these treatments and draw similarities between the two tumors.
Clinical Practice Guidelines for Pancreatic Cancer 2019 From the Japan Pancreas Society
Authors: Okusaka Takuji , Nakamura Masafumi , Yoshida Masahiro , Kitano Masayuki , Uesaka Katsuhiko , Ito Yoshinori , Furuse Junji , Hanada Keiji , Okazaki Kazuichi 
Published: March 2020

Objectives
Clinical Practice Guidelines for Pancreatic Cancer were first published in 2006 by the Japan Pancreas Society, and they were revised in 2009, 2013, and 2016. In July 2019, the Clinical Practice Guidelines for Pancreatic Cancer 2019 were newly revised in Japanese.

Methods
For this version, we developed the new guidelines according to the Minds Manual for Guideline Development 2017, which includes the concepts of GRADE (Grading Recommendations Assessment, Development, and Evaluation), to enable a better understanding of the current guidelines.

Results
The guidelines show algorithms for the diagnosis, treatment, and chemotherapy of pancreatic cancer and address 7 subjects: diagnosis, surgical therapy, adjuvant therapy, radiation therapy, chemotherapy, stent therapy, and supportive and palliative medicine. They include 56 clinical questions and 84 statements. There are statements corresponding to clinical questions, evidence levels, recommendation strengths, and agreement rates.

Conclusions
These guidelines represent the most standard clinical and practical management guidelines at this time in Japan. This is the English synopsis of the Clinical Practice Guidelines for Pancreatic Cancer 2019 in Japanese and is an attempt to disseminate the Japanese guidelines worldwide for introducing the Japanese approach for clinical management of pancreatic cancer.
Single Cell Transcriptional Archetypes of Airway Inflammation in Cystic Fibrosis
Authors: Schupp Jonas C. , Khanal Sara , Gomez Jose L. , Sauler Maor , Adams Taylor S. , Chupp Geoffrey L. , Yan Xiting , Poli Sergio , Montgomery Ruth R. , Rosas Ivan O. , Cruz Charles S. Dela , Bruscia Emanuela M. , Egan Marie E. , Kaminski Naftali , Britto Clemente J. 
Published: March 2020

AbstractCystic fibrosis (CF) is a life-shortening multisystem hereditary disease caused by abnormal chloride transport. CF lung disease is driven by innate immune dysfunction that perpetuates inflammation. The airways provide a window into CF pathogenesis, as immune cells display exaggerated inflammatory responses and impaired phagocytic function, contributing to tissue injury. In order to define the transcriptional profile of this airway immune dysfunction, we performed the first single-cell transcriptome characterization of CF sputum. We show that the airway immune cell repertoire shifted from alveolar macrophages in HC to a predominance of recruited monocytes and neutrophils in CF. Recruited lung mononuclear phagocytes were abundant in CF, separated into three archetypes: activated monocytes, monocyte-derived macrophages, and heat-shock activated monocytes. Neutrophils were most prevalent in CF, with a dominant immature proinflammatory archetype. While CF monocytes exhibited proinflammatory features, both monocytes and neutrophils showed transcriptional evidence of abnormal phagocytic and cell-survival programs. Our findings offer an opportunity to understand subject-specific immune dysfunction and its contribution to divergent clinical courses in CF. As we progress towards personalized applications of therapeutic and genomic developments, we hope this inflammation profiling approach will enable further discoveries that change the natural history of CF lung disease.