bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of Medicare Drug Subsidies on Adherence for Diabetics: Evidence From a Regression Discontinuity Design
Authors: Glynn Alexandra , Hernandez Inmaculada , Roberts Eric 
Published: December 2020

Abstract
Out-of-pocket prescription drug costs are rapidly rising, particularly for insulin, which is a life-saving drug used by 3.1 million diabetics on Medicare. High out-of-pocket costs place an accentuated financial strain on older adults with diabetes, many of whom have low incomes, and may impede medication adherence, leading to poor health outcomes. The Medicare Part D Low-Income Subsidy (LIS) program limits drug co-pays to under $8.50 per prescription and caps out-of-pocket drug costs for lowest-income recipients (&lt;135% Federal Poverty Level, FPL), resulting in pronounced differences in out-of-pocket costs for those with marginally different incomes. Using detailed income data from the Health and Retirement Study linked to Medicare claims (2008-2016), we employed a regression discontinuity (RD) design to isolate the effects of differences in out-of-pocket costs at eligibility thresholds for the LIS. Diabetic beneficiaries whose income exceeded the LIS eligibility threshold had lower Part D spending (-$945/year, p=0.03, n=2,367) and adherence to oral antidiabetic drugs (-8%, p=0.02). We conducted secondary analyses at the eligibility threshold for Medicaid, as individuals whose income exceeds the eligibility limit for Medicaid (100% of FPL in most states) are significantly less likely to receive the LIS. Above the Medicaid eligibility threshold (n=2,295), annual spending on insulin was $395 lower (p=0.002) and proportion of insulin use was 6% lower (p=0.04). These results suggest low-income Medicare beneficiaries who are not shielded from out-of-pocket costs via the LIS are particularly sensitive to drug costs. Policy proposals to limit out-of-pocket costs could improve medication adherence to high-cost drugs for vulnerable beneficiaries.
Type of Tea Consumption and Mild Cognition Impairment in Older Adults
Authors: Yao Yao , Chen Huashuai , Gu Danan , Zeng Yi 
Published: December 2020

Abstract
Existing studies have testified the neuroprotective qualities of tea. As there are several types of tea, question on which type of tea may exert substantial influence on cognitive health is intriguing and remains unknow. We aim to estimate the association between type of tea consumption and mild cognition impairment (MCI) using a nationally representative dataset of older population in China. Type of tea consumption was classified as three groups: Green, fermented (White, Oolong, Black, and Pu’eh), and flower tea. The Mini-Mental State Examination (MMSE) was adopted to assess cognitive function. We conducted multivariate logistic regressions to evaluate the association between type of tea drinking and cognition outcomes (MMSE score and MCI). Potential confounders including sociodemographic factors, health conditions, dietary patterns, lifestyles, activities of daily living, mental health, and living environments. A total of 10,923 participants (mean age: 85.4 yr; female: 53.5%) included in the study. The type of current tea consumption among the participants were: 2143 for green tea, 1302 for fermented tea, and 844 for flower tea. Compared to those who had no habit of tea consumption, the odds ratio of MCI in green tea drinkers was 0.80 (0.68-0.95), in fermented tea drinkers was 1.07 (0.89-1.30), and in flower tea drinkers were 0.85 (0.67-1.09). Our study showed green tea and flower tea consumption associated with lower odds of MCI, while the association was not found among fermented tea drinkers. Future experimental and longitudinal studies are warranted to illustrate the association between varied type of tea and cognitive health.
Trends in Disability Among Adults 55-64 in the United States and England From 2002 to 2016
Authors: Choi HwaJung , Schoeni Robert , Cho Tsai-Chin , Langa Kenneth 
Published: December 2020

Abstract
The paper’s goal is to assess whether and, if so, the extent to which prevalence in disability of adults near retirement ages in the US increased over time compared to their peers in England and examine income group differences in the relative trends. This study uses 2002-2016 Health and Retirement Study (HRS) and English Longitudinal Study of Ageing (ELSA) focusing on adults aged 55-64. Annual percent changes over the period of 2002-2016 for limitations in instrumental activities of daily living (IADL) and activities of daily living (ADL) are estimated for each survey (HRS and ELSA) using multivariable logistic regressions to adjust for individual-level characteristics While disability prevalence of adults ages 55-64 in England improved over the years of 2002-2016 (annual % change= -2.01 for IADL; - 2.53 for ADL), disability prevalence of US adults has not improved and in fact even worsened in terms of IADL (annual % change= +1.35). There are substantial variations in the IADL/ADL trends by income groups. In the US, the adverse trends in disability were more pronounced among the lowest income groups (annual % change in IADL=1.76 for bottom 20% vs. -2.08 for top 20%; annual % change in ADL=1.08 for bottom 20% vs. -2.08 for top 20%). In England, the disability status improved over time for all but the lowest income group. We will examine further to identify specific factors contributing to divergent/convergent trends in disability between the US and England.
Microtubule-associated protein 1B dysregulates microtubule dynamics and neuronal mitochondrial transport in spinal muscular atrophy
Authors: Bora Gamze , Hensel Niko , Rademacher Sebastian , Koyunoğlu Dila , Sunguroğlu Merve , Aksu-Mengeş Evrim , Balcı-Hayta Burcu , Claus Peter , Erdem-Yurter Hayat 
Published: December 2020

AbstractSpinal muscular atrophy (SMA) is a devastating childhood disease primarily affecting lower motoneurons in the spinal cord. SMA is caused by the loss of functional survival of motoneuron (SMN) protein, leading to structural and functional alterations of the cytoskeleton in motoneurons and other cells. Loss of SMN results in impairments of microtubule architecture, but the underlying mechanisms are not completely understood. In this study, we mechanistically analyzed the effects of SMN deficiency on microtubules, demonstrating a reduced stability together with a reduction in alpha tubulin detyrosination. This was caused by increased levels of microtubule-associated protein 1B and tubulin tyrosine ligase, resulting in mitochondrial mislocalization in SMA. Our findings suggest that altered tubulin post-translational modifications and microtubule-associated proteins are involved in the pathomechanisms of SMA, such as an impaired axonal transport of mitochondria.
Effective antimicrobial combination in vivo treatment predicted with microcalorimetry screening
Authors: Kragh Kasper Nørskov , Gijón Desiree , Maruri Ainhize , Antonelli Alberto , Coppi Marco , Kolpen Mette , Crone Stephanie , Tellapragada Chaitanya , Hasan Badrul , Radmer Stine , de Vogel Corné , van Wamel Willem , Verbon Annelies , Giske Christian G , Rossolini Gian Maria , Cantón Rafael , Frimodt-Møller Niels 
Published: December 2020

Abstract

Objectives
The worldwide emergence of antibiotic resistance calls for effective exploitation of existing antibiotics. Antibiotic combinations with different modes of action can synergize for successful treatment. In the present study, we used microcalorimetry screening to identify synergistic combination treatments against clinical MDR isolates. The synergistic effects were validated in a murine infection model.

Methods
The synergy of meropenem combined with colistin, rifampicin or amikacin was tested on 12 isolates (1 Escherichia coli, 5 Klebsiella pneumoniae, 3 Pseudomonas aeruginosa and 3 Acinetobacter baumannii) in an isothermal microcalorimeter measuring metabolic activity. One A. baumannii strain was tested with two individual pairings of antibiotic combinations. The microcalorimetric data were used to predict in vivo efficacy in a murine peritonitis/sepsis model. NMRI mice were inoculated intraperitoneally and after 1 h treated with saline, drug X, drug Y or X+Y. Bacterial load was determined by cfu in peritoneal fluid and blood after 4 h.

Results
In vitro, of the 13 combinations tested on the 12 strains, 3 of them exhibited a synergistic reduction in MIC (23% n = 3/13), 5 showed an additive effect (38.5% n = 5/13) and 5 had indifferent or antagonistic effects (38.5% n = 5/13). There was a significant correlation (P = 0.024) between microcalorimetry-screening FIC index values and the log reduction in peritoneal fluid from mice that underwent combination treatment compared with the most effective mono treatment. No such correlation could be found between chequerboard and in vivo results (P = 0.16).

Conclusions
These data support microcalorimetic metabolic readout to predict additive or synergistic effects of combination treatment of MDR infections within hours.
SUMOylation of α-tubulin is a novel modification regulating microtubule dynamics
Authors: Feng Wenfeng , Liu Rong , Xie Xuan , Diao Lei , Gao Nannan , Cheng Jinke , Zhang Xu , Li Yong , Bao Lan 
Published: December 2020

Abstract
Microtubules (MTs) are regulated by a number of known posttranslational modifications (PTMs) on α/β-tubulin to fulfill diverse cellular functions. Here, we showed that SUMOylation is a novel PTM on α-tubulin in vivo and in vitro. The SUMOylation on α-tubulin mainly occurred at Lys 96 (K96), K166, and K304 of soluble α-tubulin and could be removed by small ubiquitin-related modifier (SUMO)-specific peptidase 1. In vitro experiments showed that tubulin SUMOylation could reduce interprotofilament interaction, promote MT catastrophe, and impede MT polymerization. In cells, mutation of the SUMOylation sites on α-tubulin reduced catastrophe frequency and increased the proportion of polymerized α-tubulin, while upregulation of SUMOylation with fusion of SUMO1 reduced α-tubulin assembly into MTs. Additionally, overexpression of SUMOylation-deficient α-tubulin attenuated the neurite extension in Neuro-2a cells. Thus, SUMOylation on α-tubulin represents a new player in the regulation of MT properties.
Bulges in left-handed G-quadruplexes
Authors: Das Poulomi , Ngo Khac Huy , Winnerdy Fernaldo Richtia , Maity Arijit , Bakalar Blaž , Mechulam Yves , Schmitt Emmanuelle , Phan Anh Tuân 
Published: December 2020

Abstract
G-quadruplex (G4) DNA structures with a left-handed backbone progression have unique and conserved structural features. Studies on sequence dependency of the structures revealed the prerequisites and some minimal motifs required for left-handed G4 formation. To extend the boundaries, we explore the adaptability of left-handed G4s towards the existence of bulges. Here we present two X-ray crystal structures and an NMR solution structure of left-handed G4s accommodating one, two and three bulges. Bulges in left-handed G4s show distinct characteristics as compared to those in right-handed G4s. The elucidation of intricate structural details will help in understanding the possible roles and limitations of these unique structures.
Adjuvant Radiotherapy Versus Watchful Waiting for World Health Organization Grade II Atypical Meningioma: A Single-Institution Experience
Authors: Bray David P , Quillin Joseph W , Press Robert H , Yang Yilin , Chen Zhengjia , Eaton Bree R , Olson Jeffrey J 
Published: December 2020

Abstract

BACKGROUND
Atypical meningiomas (AMs) are meningiomas that have a higher rate of recurrence than grade I meningioma. Due to the higher risk of recurrence, adjuvant radiotherapy (RT) after resection of AM has been employed. At our institution, some neurosurgeons employ adjuvant RT on all primarily resected AMs, while others employ watchful waiting with serial imaging.

OBJECTIVE
To study the effect of adjuvant RT on newly resected AMs.

METHODS
A retrospective review of all AMs primarily resected at our institution from 1996 to 2018 was completed. Data on patient demographics, radiographic findings, use of adjuvant RT, time of follow-up, and recurrences were collected. Adjuvant RT was defined as RT that occurred within 6 mo of initial resection.

RESULTS
A total of 162 patients met the inclusion criteria. Gross total resection was achieved in 73% of cases. Average time until recurrence in the cohort was 37 mo. A total of 108 patients had adjuvant RT, while 54 patients did not. On multivariate survival analysis, sex, Simpson grade resection, and use of adjuvant RT were independent predictors of recurrence. Mean time to recurrence in patients who received adjuvant RT was 43.7 mo versus 34.7 mo for those who did not receive adjuvant RT.

CONCLUSION
This study includes the largest retrospective cohort of patients who have received adjuvant RT after primary resection of AM. Our results suggest that the use of adjuvant RT is independently associated with a lower chance of recurrence. These data suggest that practitioners can consider the use of adjuvant RT for newly resected AMs, regardless of Simpson grade resection.
Predicting Discharge Disposition Following Meningioma Resection Using a Multi-Institutional Natural Language Processing Model
Authors: Muhlestein Whitney E , Monsour Meredith A , Friedman Gabriel N , Zinzuwadia Aniket , Zachariah Marcus A , Coumans Jean-Valery , Carter Bob S , Chambless Lola B 
Published: December 2020

Abstract

BACKGROUND
Machine learning (ML)-based predictive models are increasingly common in neurosurgery, but typically require large databases of discrete variables for training. Natural language processing (NLP) can extract meaningful data from unstructured text.

OBJECTIVE
To present an NLP model that predicts nonhome discharge and a point-of-care implementation.

METHODS
We retrospectively collected age, preoperative notes, and radiology reports from 595 adults who underwent meningioma resection in an academic center from 1995 to 2015. A total of 32 algorithms were trained with the data; the 3 best performing algorithms were combined to form an ensemble. Predictive ability, assessed by area under the receiver operating characteristic curve (AUC) and calibration, was compared to a previously published model utilizing 52 neurosurgeon-selected variables. We then built a multi-institutional model by incorporating notes from 693 patients at another center into algorithm training. Permutation importance was used to analyze the relative importance of each input to model performance. Word clouds and non-negative matrix factorization were used to analyze predictive features of text.

RESULTS
The single-institution NLP model predicted nonhome discharge with AUC of 0.80 (95% CI = 0.74-0.86) on internal and 0.76 on holdout validation compared to AUC of 0.77 (95% CI = 0.73-0.81) and 0.74 for the 52-variable ensemble. The multi-institutional model performed similarly well with AUC = 0.78 (95% CI = 0.74-0.81) on internal and 0.76 on holdout validation. Preoperative notes most influenced predictions. The model is available at http://nlp-home.insds.org.

CONCLUSION
ML and NLP are underutilized in neurosurgery. Here, we construct a multi-institutional NLP model that predicts nonhome discharge.
Pathogenesis and Classification of Paracocidioidomycosis: New Insights From Old Good Stuff
Authors: Benard Gil 
Published: December 2020

AbstractDifferent classifications of paracoccidioidomycosis emerged since its discovery in 1908, culminating in the proposition of a simplified and consensual one in 1987. However, by revisiting these classifications, case reports, or case series from which the authors based their own, we found many patients who did not fit in either the 1987 classification or in the correspondent natural history/pathogenesis view. In this report, the concepts of paracoccidioidomycosis infection, primary pulmonary paracoccidioidomycosis (PP-PCM), and other subclinical forms of PCM are reassessed. A classification is proposed to encompass all these subtle but distinct outcomes. I suggest a continuum between the PP-PCM and the overt chronic form of disease, and not the current view of quiescent foci, frozen in time and suddenly reactivated for unknown reasons. Failure to fully resolve the infection in its initial stages is a conceivable hypothesis for the chronic form. The proposed clinical classification might offer new insights to better characterize and manage PCM patients.
Introduction
Authors: Van Schaack Beth 
Published: December 2020

Abstract
This chapter introduces the conflict in Syria, the various impediments to justice, and the book’s broad themes, including the observation that the paralysis in the U.N. Security Council has spurred a form of forced creativity that has generated a number of novel proposals for how to bring justice to Syria. In addition to providing an overview of the text, this introduction also presents the matrix of accountability that will structure the core of the book. This matrix is organized along two axes: the first (x) is premised on the distinction between criminal and civil liability; the second (y) compares the types of justice institutions and legal authorities that are available to bring individual perpetrators and even Syria as a sovereign state to justice. The remainder of the book explores different routes to accountability through this matrix and the various advantages presented by, and the challenges encumbering, the various justice options when it comes to the situation in Syria.
A Short History of a Long Conflict
Authors: Van Schaack Beth 
Published: December 2020

Abstract
This introductory chapter offers a short history of the eight-year conflict in Syria, covering the arrival of the Arab Spring, the transformation of a long-overdue revolution into a full-scale armed conflict, and the evolution of the situation on the ground to date. This chapter prefaces the contemporary violence with a few historical events, surfacing atrocities committed in the 1980s that have never been the subject of any genuine accountability process as well as the entrenchment of authoritarianism under the House of Assad. It describes how the arrival of the Arab Spring reawakened long-dormant revolutionary impulses, which amplified the government’s repression. This, in turn, provoked an armed resistance and a full-scale conflict, which opened space for the arrival of the Islamic State of Iraq and the Levant (ISIL). The chapter recounts this history with reference to several key events and factors: the response of the international community, the opposition’s perpetual rearrangements, the appearance of ISIL, the commission of war crimes and crimes against humanity (including the infringement of the taboo against chemical weapons), the humanitarian catastrophe that ensued, forms of foreign intervention (aid, arms, and air strikes), and failed peace processes. In addition to recounting the involvement of major Western powers in the Syrian battlespace, it also touches upon the impact of spillover conflicts in the subregion. Others will write the definitive history of this tragedy; the goal here is to touch upon key milestones as this conflict unfolded and to set the scene for the efforts to promote justice and accountability for the atrocities underway.
Deconstructing the Would-Be Referral
Authors: Van Schaack Beth 
Published: December 2020

Abstract
The previous chapter ended with France’s failed attempt to refer the situation in Syria to the International Criminal Court (ICC). After briefly surveying the history of the U.N. Security Council’s engagement with international justice, chapter 4 deconstructs the failed ICC referral draft proffered by France with an eye toward explaining the origins, import, impact, and criticism of several textual elements contained within prior Security Council referrals and France’s draft text (e.g., the provisions that seek to divest the ICC of jurisdiction over the nationals of non-state parties, the prohibition on U.N. funding, the endurance of immunities that potential ICC defendants might enjoy, and the anodyne state cooperation language). Although many (but not all) of these provisions reappeared in the Syria referral draft, subtle textual changes suggest movement on some of the more contentious issues. In an effort to achieve consensus, drafters also devised inventive yet inconspicuous means to cabin the ICC’s jurisdiction; these compromises may or may not be accepted by the Court if it were ever to be allowed to move forward. Because many of the most contentious provisions in the Council’s ICC referral resolutions owe their provenance to concerns of the United States, the draft resolution also presents a microcosm of the United States’ Security Council practice when it comes to advancing international justice.
Transitional Justice without Transition
Authors: Van Schaack Beth 
Published: December 2020

Abstract
The penultimate chapter offers a discussion of the prospects for a genuine transitional justice process in Syria. Chapter 10 begins with a short history of the development of the archetypal tools within the transitional justice toolkit—criminal accountability, truth commissions, reparations, amnesties, lustration, institutional reform, and guarantees of nonrecurrence—and the way in which transitional justice efforts have become increasingly internationalized. This enhanced involvement of the international community in promoting transitional justice reflects the belief—premised on historical case studies and emerging empirical research—that societies in transition must address the crimes of the past in some capacity or risk their repetition. The chapter surveys the most recent research testing these claims, which has benefited from the creation of a number of new databases gleaned from states in transition. The chapter then describes ways in which the international community has tried to prepare for a future transitional justice process in Syria even in the absence of a political transition, including by training Syrian advocates, surveying Syrian communities to understand their knowledge of transitional justice and preferences for Syria, promoting psychosocial rehabilitation and solidarity among victims, and preparing for truth-telling exercises and institutional reform measures. The conclusion suggests ways in which the international community could still promote some form of transitional justice as part of the reconstruction process, even if Assad remains in power, which seems increasingly likely.
Human Self-Reflective Curse
Authors: Rochat Philippe 
Published: December 2020

Abstract
Moral hypocrisy and duplicity are the rule rather than just exceptions. Both are inseparable from self-consciousness and humans’ unique concern for reputation. It is linked to face-maintenance (keeping apparent moral self-unity) in the midst of obvious contradictions. Powerful examples abound, such as the fact that Hitler was a vegetarian. We are indeed moral acrobats, and this has its roots in self-consciousness, the pillar of our human nature. Self-conscious psychology leads toward obligatory existential rumination of deeply unsettling existential truths. These truths shape our moral sense, in particular what we feel and construe as right or wrong and what we experience and reason as just or unjust.