bluuebunny/crossref_metadata_2025_split huggingface dataset:
A single-institution retrospective analysis of pathologically determined malignant transformation in IDH mutant glioma patients
Authors: Liu Vicki , Wetzel Ethan A , Eldred Blaine S C , Zapanta Rinonos Serendipity , Prins Terry J , Khanlou Negar , Liau Linda M , Chong Robert , Nghiemphu Phioanh L , Cloughesy Timothy F , Ellingson Benjamin M , Lai Albert 
Published: April 2023

Abstract

Background
Lower-grade IDH mutant glioma patients frequently undergo malignant transformation (MT), with apparent worse prognosis. Many studies examine MT in mixed IDH status cohorts and define MT using imaging, not histopathology. Our study examines the timing, predictors, and prognostic implications of pathologically determined MT in a large, exclusively IDH mutant cohort.

Methods
We identified 193 IDH mutant lower-grade glioma patients at UCLA who received multiple surgeries. We examined the outcomes of pathologically determined MT patients.

Results
Time to MT is longer in grade 2 oligodendroglioma (G2 Oligo) than in grade 2 astrocytoma (G2 Astro) (HR = 0.46, P = .0007). The grade 3 astrocytoma (G3 Astro) to grade 4 astrocytoma (G4 Astro) interval is shorter in stepwise MT (G2 to G3 to G4 Astro) patients than in initial G3 Astro patients (P = .03). Novel contrast enhancement had 65% positive predictivity, 67% negative predictivity, 75% sensitivity, and 55% specificity in indicating pathologically defined MT. In G2 Astro, initial gross total resection delayed MT (HR = 0.50, P = .02) and predicted better overall survival (OS) (HR = 0.34, P = .009). In G2 Oligo, spontaneous MT occurred earlier than treated MT (HR = 11.43, P = .0002), but treatment did not predict improved OS (P = .8). MT patients (n = 126) exhibited worse OS than non-MT patients (n = 67) in All (HR = 2.54, P = .0009) and G2 Astro (HR = 4.26, P = .02).

Conclusion
Our study expands the understanding of MT to improve IDH mutant lower-grade glioma management.
The brain-penetrant cell-cycle inhibitor p28 sensitizes brain metastases to DNA-damaging agents
Authors: Mander Sunam , Gorman Gregory S , Coward Lori U , Christov Konstantin , Green Albert , Das Gupta Tapas K , Yamada Tohru 
Published: April 2023

Abstract

Background
Brain metastases (BMs), the most common tumors of the central nervous system, are life-threatening with a dismal prognosis. The major challenges to developing effective treatments for BMs are the limited abilities of drugs to target tumors and to cross the blood-brain barrier (BBB). We aimed to investigate the efficacy of our therapeutic approach against BMs in mouse models that recapitulate the clinical manifestations of BMs.

Methods
BMs mouse models were constructed by injecting human breast, lung cancer, and melanoma intracardially, which allowed the BBB to remain intact. We investigated the ability of the cell-penetrating peptide p28 to cross the BBB in an in vitro 3D model and in the BMs animal models. The therapeutic effects of p28 in combination with DNA-damaging agents (radiation and temozolomide) on BMs were also evaluated.

Results
p28 crossed the intact BBB more efficiently than the standard chemotherapeutic agent, temozolomide. Upon crossing the BBB, p28 localized preferentially to tumor lesions and enhanced the efficacy of DNA-damaging agents by activating the p53-p21 axis. In the BMs animal models, radiation in combination with p28 significantly reduced the tumor burden of BMs.

Conclusions
The cell-cycle inhibitor p28 can cross the BBB localize to tumor lesions in the brain and enhance the inhibitory effects of DNA-damaging agents on BMs, suggesting the potential therapeutic benefits of this molecule in BMs.
Longer-term structural transitions and short-term macroeconomic adjustment: quantitative implications for the global financial system
Authors: McKibbin Warwick , Vines David 
Published: April 2023

AbstractThis paper provides quantitative modelling of the effect of three longer-term global transitions: the global demographic transition involving a marked reduction in population growth; a long-term slowdown in productivity growth which may continue, or may conceivably be reversed; and the disruption in the global economy due to increasing climate shocks and the implementation of climate policies that will be needed to reach net-zero emissions by 2050. We study the global investment needs to which these transitions will lead. We demonstrate that these investment needs will be both asymmetric across countries and over time. This asymmetry will lead to potentially large changes in trade flows and significant financial capital flows across national borders, and also to substantial real exchange changes and interest rate movements. The resulting large movements in international capital flows will have significant implications for the global financial system, which we demonstrate at the country and regional level.
The IMF’s journey on capital controls: what is the destination?
Authors: Ostry Jonathan D 
Published: April 2023

AbstractThe International Monetary Fund’s Articles of Agreement give countries wide latitude to regulate cross-border capital movements, subject mainly to the proviso that such regulations not be used to manipulate the exchange rate for the purpose of gaining an unfair competitive advantage. Beginning from the 1990s, however, the IMF has seemed far more supportive of fully open capital accounts than its legal framework. This can be seen not only in the institutional push to amend the Articles to enshrine fully open capital accounts in the mid-1990s, but also in subsequent speeches by IMF managing directors impugning capital controls and recent attempts to codify a set of highly restrictive circumstances under which countries may avail themselves of external financial regulations. This history suggests that, institutionally, the IMF would be far more comfortable with an architecture in which countries (strive to) eliminate restrictions on cross-border capital movements than with the vision of capital controls enshrined in its constitution by the IMF’s founding fathers, Keynes and White.
Development finance cooperation amidst great power competition: what role for the World Bank?
Authors: Morris Scott 
Published: April 2023

AbstractThe World Bank today faces parallel challenges to its operations and governance. The institution has since its founding provided financing on favourable terms to developing country governments to support national development efforts. Alongside these country demands, there are now calls for a new set of mandates and activities associated with global public goods. Advocates would have the Bank allocate large sums toward climate mitigation, pandemic response and preparedness, and other activities that may or may not align with national priorities in developing countries. The ability of the World Bank to strike an appropriate balance between country demands and global goods depends on the institution’s shareholders. Yet, the deterioration in the bilateral relationship between the United States and China now threatens to undermine effective governance at the institution. This paper considers the challenge of competing demands on World Bank resources and the degree to which a resolution could depend on an agreement between the United States and China, one that sets the strategic direction of the institution and addresses the growing impasse on the question of China’s shareholding in the Bank.
Fifty years on: what the Bretton Woods System can teach us about global macroeconomic policy-making
Authors: Subacchi Paola , Vines David 
Published: April 2023

AbstractThis paper first describes the Bretton Woods system: its origin, what it was meant to achieve, and why it collapsed. We then describe the emergence of the global non-system in which inflation targeting has replaced full-employment Keynesianism and floating exchange rates have replaced the Bretton Woods set-up of fixed but adjustable exchange rates. We describe how the Bretton Woods system set about achieving the three objectives laid down for a well-functioning international economic system by John Maynard Keynes: full employment without inflation, sustainable current account balances between countries, and a sustainable flow of international financial capital—on the understanding that an open trading regime is also fostered. Because the global non-system is now very different from the Bretton Woods system, Keynes’s objectives now need to be achieved in a very different manner. Looking forward, this non-system faces a number of longer-term challenges. Important adjustment issues will arise in relation to the global demographic transition; the potential long-term slowdown in productivity growth; and the rise in investment in renewable sources of energy which will be necessary to help ensure that the world is able to move towards zero emissions of carbon by 2050. We also discuss important policy issues in relation to the flows of international capital to emerging market economies, and the likely need for a sovereign debt reconstruction mechanism. We then go on to consider two significant structural changes to the world—the emergence of the European Monetary Union and the rise of China. A final section of the paper considers the importance of leadership in this global non-system.
From the Bretton Woods system to the global non-system: the trials and tribulations of slow learning
Authors: Vines David , Subacchi Paola 
Published: April 2023

AbstractIn this paper we analyse why an understanding of the global ‘non-system’, in which we now live, took so long to arrive after the Bretton Woods system collapsed in 1971. We first describe how knowledge of how an inflation-targeting regime would operate—what we call ‘Taylor-rule macroeconomics’—was only gradually created during the 1970s, 1980s, and 1990s. We then describe how, subsequent to this, an awareness emerged, also gradually, of how the international non-system might work, depending, as it does, on Taylor-rule macroeconomics being already in place. We then discuss the Great Moderation, making clear that a well-functioning global non-system would require not just inflation targeting and floating exchange rates in each country, but also adequate fiscal discipline, and a satisfactory form of financial regulation. We describe how a well-functioning version of this global non-system would actually fit together. We then discuss how this non-system has responded to two enormous challenges of the last 15 years, namely the Global Financial Crisis and the Covid pandemic. This discussion of what has happened in the recent past provides the background to a discussion, in the companion paper by Subacchi and Vines in this issue of the Oxford Review of Economic Policy, of the challenges that the global non-system will face in the future.
Quiet wakefulness: the influence of intraperitoneal and intranasal oxytocin on sleep–wake behavior and neurophysiology in rats
Authors: Raymond Joel S , Everett Nicholas A , Gururajan Anand , Bowen Michael T 
Published: April 2023

Abstract

Study Objectives
Exogenous administration of the neuropeptide oxytocin exerts diverse effects on various neurobehavioral processes, including sleep and wakefulness. Since oxytocin can enhance attention to social and fear-related environmental cues, it should promote arousal and wakefulness. However, as oxytocin can attenuate stress, reduce activity, and elicit anxiolysis, oxytocin might also prime the brain for rest, and promote sleep. At present, little research has comprehensively characterized the neuropsychopharmacology of oxytocin-induced effects on sleep–wake behavior and no reconciliation of these two competing hypotheses has been proposed.

Methods
This study explored the effects of oxytocin on sleep–wake outcomes using radiotelemetry-based polysomnography in adult male and female Wistar rats. Oxytocin was administered via intraperitoneal (i.p.; 0.1, 0.3 and 1 mg·kg−1) and intranasal (i.n.; 0.06, 1, 3 mg·kg−1) routes. Caffeine (i.p. and i.n.; 10 mg·kg−1) was administered as a wake-promoting positive control. To ascertain mechanism of action, pretreatment experiments with the oxytocin receptor (OXTR) antagonist L-368,899 (i.p.; 5 mg·kg−1) followed by oxytocin (i.p.; 1 mg·kg−1) were also conducted.

Results
In both male and female rats, i.p. oxytocin promoted quiet wakefulness at the cost of suppressing active wakefulness, non-rapid eye movement (NREM) and rapid eye movement (REM) sleep. Several i.p. oxytocin-induced sleep–wake effects were mediated by OXTR binding. In contrast, i.n. oxytocin did not alter most sleep–wake outcomes at any dose tested. Both i.p. and i.n. caffeine demonstrated wake-promoting effects.

Conclusions
These findings help reconcile competing hypotheses of oxytocin-induced effects on sleep–wake behavior: i.p. oxytocin promotes quiet wakefulness—a state of restful environmental awareness compatible with both oxytocin’s anxiolytic effects and its enhancement of processing complex stimuli.
Patterns of physical, chemical, and metabolic characteristics of sugar maple leaves with depth in the crown and in response to nitrogen and phosphorus addition
Authors: Young Alexander R , Minocha Rakesh , Long Stephanie , Drake John E , Yanai Ruth D 
Published: April 2023

Abstract
Few previous studies have described the patterns of leaf characteristics in response to nutrient availability and depth in the crown. Sugar maple has been studied for both sensitivity to light, as a shade-tolerant species, and sensitivity to soil nutrient availability, as a species in decline due to acid rain. To explore leaf characteristics from the top to bottom of the canopy, we collected leaves along a vertical gradient within mature sugar maple crowns in a full-factorial nitrogen (N) by phosphorus (P) addition experiment in three forest stands in central New Hampshire, USA. Thirty-two of the 44 leaf characteristics had significant relationships with depth in the crown, with the effect of depth in the crown strongest for leaf area, photosynthetic pigments and polyamines. Nitrogen addition had a strong impact on the concentration of foliar N, chlorophyll, carotenoids, alanine and glutamate. For several other elements and amino acids, N addition changed patterns with depth in the crown. Phosphorus addition increased foliar P and boron (B); it also caused a steeper increase of P and B with depth in the crown. Since most of these leaf characteristics play a direct or indirect role in photosynthesis, metabolic regulation or cell division, studies that ignore the vertical gradient may not accurately represent whole-canopy performance.
Long-term Morbidity in Patients After Surgical Correction of Adult Spinal Deformity
Authors: Imbo Bailey , Williamson Tyler , Joujon-Roche Rachel , Krol Oscar , Tretiakov Peter , Ahmad Salman , Bennett-Caso Claudia , Schoenfeld Andrew J. , Dinizo Michael , De La Garza-Ramos Rafael , Janjua M. Burhan , Vira Shaleen , Ihejirika-Lomedico Rivka , Raman Tina , O’Connell Brooke , Maglaras Constance , Paulino Carl , Diebo Bassel , Lafage Renaud , Lafage Virginie , Passias Peter G. 
Published: April 2023

Study Design.
Retrospective.

Objective.
The objective of this study is to describe the rate of postoperative morbidity before and after two-year (2Y) follow-up for patients undergoing surgical correction of adult spinal deformity (ASD).

Summary of Background Data.
Advances in modern surgical techniques for deformity surgery have shown promising short-term clinical results. However, the permanence of radiographic correction, mechanical complications, and revision surgery in ASD surgery remains a clinical challenge. Little information exists on the incidence of long-term morbidity beyond the acute postoperative window.

Methods.
ASD patients with complete baseline and five-year (5Y) health-related quality of life and radiographic data were included. The rates of adverse events, including proximal junctional kyphosis (PJK), proximal junctional failure (PJF), and reoperations up to 5Y were documented. Primary and revision surgeries were compared. We used logistic regression analysis to adjust for demographic and surgical confounders.

Results.
Of 118 patients eligible for 5Y follow-up, 99(83.9%) had complete follow-up data. The majority were female (83%), mean age 54.1 years and 10.4 levels fused and 14 undergoing three-column osteotomy. Thirty-three patients had a prior fusion and 66 were primary cases. By 5Y postop, the cohort had an adverse event rate of 70.7% with 25 (25.3%) sustaining a major complication and 26 (26.3%) receiving reoperation. Thirty-eight (38.4%) developed PJK by 5Y and 3 (4.0%) developed PJF. The cohort had a significantly higher rate of complications (63.6% vs. 19.2%), PJK (34.3% vs. 4.0%), and reoperations (21.2% vs. 5.1%) before 2Y, all P<0.01. The most common complications beyond 2Y were mechanical complications.

Conclusions.
Although the incidence of adverse events was high before 2Y, there was a substantial reduction in longer follow-up indicating complications after 2Y are less common. Complications beyond 2Y consisted mostly of mechanical issues.
Two is company, is three a crowd? Triplet therapy, novel molecular targets, and updates on the management of advanced renal cell carcinoma
Authors: Goodstein Taylor , Yang Yuanquan , Runcie Karie , Srinivasan Ramaprasad , Singer Eric A. 
Published: April 2023

Purpose of review
The purpose of this review is to highlight the most recent changes in the management of advanced renal cell carcinoma, a complicated and ever-changing field of research.

Recent findings
A recent meta-analysis examining combination therapy favors nivolumab plus cabozantinib as the overall survival leader in doublet therapy. Initial results on the first ever trial of triplet therapy have demonstrated improved progression-free survival over current standard of care. The hypoxia-inducible factor-2α (HIF-2α) inhibitor belzutifan is FDA approved for patients with von Hippel-Lindau disease and is currently being investigated in patients with nonhereditary renal cell carcinoma. The new glutamate synthesis inhibitor, telaglenastat, perhaps confers synergistic benefit when combined with everolimus, but combination with cabozantinib was not so effective. Dual mammalian target of rapamycin (mTOR) inhibition with sapanisertib does not appear to be an effective therapeutic option. New biomarkers and targets are actively being investigated. Four recent trials examining alternative agents to pembrolizumab in the adjuvant setting did not demonstrate an improvement in recurrence-free survival. Cytoreductive nephrectomy in the combination therapy era is supported by retrospective data; clinical trials are recruiting patients.

Summary
The last year ushered in novel approaches of varying success for managing advanced renal cell carcinoma, including triplet therapy, HIF-2α inhibitors, metabolic pathway inhibitors, and dual mTOR inhibitors. Pembrolizumab remains the only modern therapy available in the adjuvant setting, and the waters surrounding cytoreductive nephrectomy are still murky.
What Is the Efficacy of Intra-articular Injections in the Treatment of Ankle Osteoarthritis? A Systematic Review
Authors: Paget Liam D. A. , Mokkenstorm Milo J. , Tol Johannes L. , Kerkhoffs Gino M. M. J. , Reurink Gustaaf 
Published: April 2023

Abstract

Background
Ankle osteoarthritis (OA) is painful and can impact a patient’s physical and mental quality of life. Although intra-articular injections are commonly used to alleviate symptoms, there is conflicting evidence concerning their efficacy. Therefore, an updated systematic review would be informative.

Question/purpose
In this systematic review, we asked: Are there clinically important benefits or harms associated with the use of intra-articular injections in the treatment of ankle OA?

Methods
We used PubMed, Embase, and the Cochrane Library to search for randomized controlled trials on intra-articular injections for the treatment of ankle OA in June 2021, and updated the search in January 2022; eligible dates were from the date of inception of each database through January 2022. Reference lists of eligible studies and previous reviews were manually screened. Two reviewers independently assessed studies for eligibility. We included seven studies. Three compared hyaluronic acid (HA) with saline, one compared HA with exercise, one compared four different regimens of HA [34], one compared platelet-rich plasma (PRP) with saline, and one compared botulinum toxin Type A (BoNT-A) with HA. A total of 340 patients were included: 141 in the HA arms, 48 in the PRP arm, 38 in the BoNT-A arm, and 113 in the saline arms. Across all studies, the mean age was 52 ± 21 years, and 35% were women (119 of 340 patients). Methodologic quality was assessed using the Cochrane Risk of Bias 2.0 tool. Of the included studies, the risk of bias was low in two studies, presented some concerns in one study, and was high in four studies. According to the Grading of Recommendations Assessment, Development, and Evaluation methodology, the level of evidence was very low for HA, moderate for PRP, and very low for BoNT-A. The level of heterogeneity was high, and we opted to perform a systematic review rather than a meta-analysis. A clinically relevant difference was based on whether the between-group difference surpassed the cutoff point determined as the minimum clinically important difference.

Results
No clinically relevant differences were found among HA, PRP, and BoNT-A and their control groups at 3, 6, or 12 months. No studies reported any serious adverse events in any treatment group.

Conclusion
Given the lack of observed efficacy in this systematic review, these treatments should not be used in practice until or unless future high-quality studies find evidence of efficacy.

Level of Evidence
Level III, therapeutic study.
Embryonic arrest: causes and implications
Authors: Sahin Gizem N. , Yildirim Raziye M. , Seli Emre 
Published: April 2023

Purpose of review
Embryonic arrest is a key determinant of the number of euploid blastocysts obtained after IVF. Here, we review factors that are implicated in the developmental arrest of preimplantation embryos and their relevance for assisted reproduction outcomes.

Recent findings
Among the treatment options available to infertile women, IVF is the one associated with most favorable outcomes. The cumulative pregnancy rates in women undergoing IVF are determined by aneuploidy rate (age), ovarian response to stimulation (ovarian reserve), and the rate of embryo developmental arrest. Mutations in maternal effect genes, especially those encoding for subcortical maternal complex, have been implicated in human embryo developmental arrest. In addition, perturbation of biological processes, such as mitochondrial unfolded protein response and long noncoding RNA regulatory pathways, may play a role. However, how each of these factors contributes to embryos’ arrest in different cohorts and age groups has not been determined.

Summary
Arrest of human embryos during preimplantation development is a common occurrence and is partly responsible for the limited number of euploid blastocysts obtained in assisted reproduction cycles. Although genetic and metabolic causes have been implicated, the mechanisms responsible for human embryo developmental arrest remain poorly characterized.