bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessment of Suvorexant and Eszopiclone as Alternatives to Benzodiazepines for Treating Insomnia in Patients With Major Depressive Disorder
Authors: Shigetsura Yuki , Imai Satoshi , Endo Hiroki , Shimizu Yumi , Ueda Keita , Murai Toshiya , Itohara Kotaro , Nakagawa Shunsaku , Yonezawa Atsushi , Ikemi Yasuaki , Fukatsu Sachio , Kitada Noriaki , Terada Tomohiro , Nakagawa Takayuki , Matsubara Kazuo 
Published: April 2022

Objectives
We investigated the utility of switching from benzodiazepines to suvorexant or eszopiclone to manage benzodiazepine-unresponsive insomnia in patients with major depressive disorder (MDD) in a randomized, open-label study.

Methods
Patients with MDD who have insomnia symptoms (a score of >7 on the Insomnia Severity Index Japanese version [ISI-J]), who had received benzodiazepine treatment for more than 2 weeks (n = 18) were randomized to 4 weeks of suvorexant (20 or 15 mg/d) or eszopiclone (3 or 2 mg/d) treatment. The primary endpoint was an improvement in insomnia severity from baseline assessed by the ISI-J score at 2 and 4 weeks after switching from benzodiazepines. The secondary endpoints included changes in the scores of the Pittsburgh Sleep Quality Index Japanese version, the Beck Depression Inventory II, Generalized Anxiety Disorder 7, the digit span test, and the digit symbol substitution test from baseline. Adverse events were recorded throughout the study.

Results
Patients taking suvorexant or eszopiclone had improved ISI-J scores (−4.3 for suvorexant and −4.1 for eszopiclone at week 4; P = 0.04 for eszopiclone). Both drugs tended to improve the Beck Depression Inventory II and Generalized Anxiety Disorder 7 scores 2 and 4 weeks after switching. The Pittsburgh Sleep Quality Index Japanese version, digit symbol substitution test, and digit span test scores and the incidence of adverse events did not change from baseline.

Conclusions
Switching to suvorexant or eszopiclone was well tolerated and improved the severity of benzodiazepine-unresponsive insomnia in MDD patients. Both drugs could be beneficial alternatives to benzodiazepines for treating insomnia in MDD patients.
Effectiveness and Safety of Early High-Efficacy Versus Escalation Therapy in Relapsing-Remitting Multiple Sclerosis in Argentina
Authors: Rojas Juan Ignacio , Patrucco Liliana , Alonso Ricardo , Garcea Orlando , Deri Norma , Carnero Contentti Edgar , Lopez Pablo A. , Pettinicchi Juan Pablo , Caride Alejandro , Cristiano Edgardo 
Published: April 2022

Escalation (ES) and early high-efficacy (EHE) therapies have been the main treatment strategies adopted in multiple sclerosis (MS) in recent years. The aim of this study was to compare the effectiveness and safety of EHE versus ES strategies in MS patients from Argentina.

Methods
This is a retrospective multicenter cohort study in Argentina. Eligible patients were categorized into 2 groups as follows: EHE if received natalizumab, ocrelizumab, rituximab, alemtuzumab, mitoxantrone, or cladribine; and ES if received interferon β, glatiramer acetate, teriflunomide, dimethyl fumarate, or fingolimod as initial therapy. The primary outcome was confirmed disability progression (Expanded Disability Status Scale [EDSS] increase). Additional outcomes included the proportion of patients and time to: EDSS 6; new relapses; new T2–magnetic resonance imaging (MRI) lesions; no evidence of disease activity; and specific adverse events. Propensity score–based nearest-neighbor matching (without replacement) was applied to homogenize the sample, and Cox regression model stratified by matched pairs was used for the analysis.

Results
After propensity score matching, 193 and 112 patients were retained in the ES and EHE groups, respectively. The EHE significantly decreased the risk of EDSS progression (hazard ratio [HR], 0.62; 95% confidence interval [95% CI], 0.40–0.98; P = 0.04), relapses (HR, 0.66; 95% CI, 0.49–0.89; P = 0.006), and new MRI activity during follow-up (HR, 0.55; 95% CI, 0.40–0.75; P < 0.001). No significant differences were observed in specific adverse events between groups.

Conclusions
Our study shows that EHE therapies prevent disease progression, relapses, and new MRI lesions and demonstrated no increased risk of specific adverse events when compared with ES therapy. These data should be considered when selecting a specific treatment for MS patients.
Patient Personality and Illness Perceptions in Relation to Follow-Up Appointment Adherence in Neuro-Ophthalmology
Authors: Aziz Rem , Bindiganavale Megha P. , Chang Robert T. , Moss Heather E. 
Published: April 2022

Background:
Improving patient attendance at medical follow-up visits may have a notable impact on disease and overall health outcomes. Understanding factors contributing to poor attendance is important for identifying at-risk patients and designing interventions to improve clinical outcomes. Our objective was to identify personality and illness perception factors associated with attendance at recommended follow-up visits in a neuro-ophthalmology practice.

Methods:
New or established patients (≥18 years) with scheduled neuro-ophthalmology (study) or glaucoma (comparison) appointments at a tertiary care academic medical center completed the Brief Illness Perception Questionnaire and Ten-Item Personality Inventory. Physician recommendations made during the visit were recorded (medications, referrals, follow-up, testing, and procedures). A chart review was performed 18 months after enrollment to assess attendance at follow-up appointment and adherence with other physician recommendations. Multiple variable logistic regression models studied associations between follow-up appointment attendance and demographic factors, appointment factors, and survey responses.

Results:
Among 152 respondents (97% response rate (152 of 157), aged 19–97 years, 58% female, 34% new, 80 neuro-ophthalmology, 72 glaucoma), neuro-ophthalmology subjects were younger, more likely to be White, non-Hispanic, female and new to the practice than subjects with glaucoma. They reported higher emotional impact, identity, and consequences related to their illness (P = 0.001–0.03). Neuro-ophthalmology physician recommendations included more referrals to other services (17.5% vs 1.4%, P = 0.001, chi-square) and more radiology studies (15% vs 0%, P = 0.001, chi-square), but fewer follow-up visits (75% vs 97%, P < 0.0005, chi-square). Among those with recommended follow-up visits, neuro-ophthalmology subjects had lower rates of on-time appointment attendance (55% vs 77%, P = 0.009, chi-square). In a multiple variable model, on-time follow-up attendance was associated with shorter recommended follow-up interval (≤90 days, P < 0.0005), established (vs new) patient status at enrollment visit (P = 0.04), and glaucoma (P = 0.08), but not subject demographics, illness perception, or personality factors.

Conclusions:
Patient demographics, illness perception, and personality traits were not associated with follow-up appointment attendance and therefore unlikely to be useful for identifying patients at risk of being lost to follow-up. New neuro-ophthalmology patients with a follow-up recommended ≥90 days in advance may benefit from targeted interventions to improve follow-up appointment adherence.
Peripapillary Microvascular and Structural Parameters in Atrophic Nonarteritic Anterior Ischemic Optic Neuropathy and Their Unaffected Fellow Eyes
Authors: Hondur Gozde , Budakoglu Ozlem 
Published: April 2022

Background:
This cross-sectional study aimed to evaluate the peripapillary vessel density (VD), peripapillary retinal nerve fiber layer (RNFL) thickness values of eyes with atrophic nonarteritic anterior ischemic optic neuropathy (NAION), and unaffected fellow eyes.

Methods:
Peripapillary VDs and RNFL thicknesses in the peripapillary region and 4 sectors (superior, inferior, nasal, and temporal) were evaluated using optical coherence tomography angiography among 19 atrophic NAION eyes, 19 unaffected fellow eyes, and 22 age-matched and sex-matched healthy controls.

Results:
The NAION eyes had lower peripapillary VD and RNFL thickness values in all areas compared with both the fellow and the healthy control eyes (P < 0.001 for all). The fellow eyes also demonstrated lower peripapillary VD values (P = 0.02) despite similar RNFL thickness values (P = 0.99) in the peripapillary region compared with the age-matched and sex-matched healthy controls. The peripapillary RNFL thickness values significantly correlated with peripapillary VD values in both NAION and fellow eyes.

Conclusions:
Diminished RNFL thickness and peripapillary VD values were observed in atrophic NAION eyes. In addition, a tendency for a lower peripapillary VD despite similar RNFL thickness values in the fellow eyes may indicate the potential vascular risk factors for NAION.
Level and duration of IgG and neutralizing antibodies to SARS-CoV-2 in children with symptomatic or asymptomatic SARS-CoV-2 infection
Authors: Khaitan Alka , Datta Dibyadyuti , Bond Caitlin , Goings Michael , Co Katrina , Odhiambo Eliud O. , Zhang Lin , Beasley Stephanie , Poorbaugh Josh , John Chandy C. 
Published: April 2022

AbstractBackgroundThere are presently conflicting data about level and duration of antibodies to SARS-CoV-2 in children after symptomatic or asymptomatic infection.MethodsWe enrolled adults and children in a prospective 6-month study in the following categories: 1) symptomatic, SARS-CoV-2 PCR+ (SP+; children, n=8; adults, n=16), 2) symptomatic, PCR- or untested (children, n=27), 3) asymptomatic exposed (children, n=13) and 4) asymptomatic, no known exposure (children, n=19). Neutralizing and IgG antibodies to SARS-CoV-2 antigens and Spike protein variants were measured by multiplex serological assays.ResultsAll SP+ children developed nAb, whereas 81% of SP+ adults developed nAb. Decline in the presence of nAb over 6 months was not significant in symptomatic children (100% to 87.5%, p=0.32) in contrast to adults (81.3 to 50.0%, p=0.03). Among all children with nAb (n=22), nAb titers and change in titers over 6 months were similar in symptomatic and asymptomatic children. Levels of IgG antibodies in children to the SARS-CoV-2 Spike, RBD-1 and -2, nucleocapsid and N-terminal domain antigens and to Spike protein variants were similar to those in adults. IgG levels to primary antigens decreased over time in both children and adults, but levels to three of six Spike variants decreased only in children.ConclusionsChildren with asymptomatic or symptomatic SARS-CoV-2 infection develop robust neutralizing antibodies that remain present longer than in adults but wane in titer over time, and broad IgG antibodies that also wane in level over time.Key PointsChildren have robust neutralizing and IgG antibody responses to SARS-CoV-2 infection after symptomatic or asymptomatic disease that are at least as strong as in adults. Neutralizing antibodies in children last longer than in adults but wane over time.
Evaluation of machine learning for predicting COVID-19 outcomes from a national electronic medical records database
Authors: Browning Sean , Lee Scott H. , Belay Ermias , DeCuir Jennifer , Cato Shana Godfred , Patel Pragna , Schwartz Noah , Wong Karen K. 
Published: April 2022

AbstractObjectiveWhen novel diseases such as COVID-19 emerge, predictors of clinical outcomes might be unknown. Using data from electronic medical records (EMR) allows evaluation of potential predictors without selecting specific features a priori for a model. We evaluated different machine learning models for predicting outcomes among COVID-19 inpatients using raw EMR data.Materials and MethodsIn Premier Healthcare Data Special Release: COVID-19 Edition (PHD-SR COVID-19, release date March, 24 2021), we included patients admitted with COVID-19 during February 2020 through April 2021 and built time-ordered medical histories. Setting the prediction horizon at 24 hours into the first COVID-19 inpatient visit, we aimed to predict intensive care unit (ICU) admission, hyperinflammatory syndrome (HS), and death. We evaluated the following models: L2-penalized logistic regression, random forest, gradient boosting classifier, deep averaging network, and recurrent neural network with a long short-term memory cell.ResultsThere were 57,355 COVID-19 patients identified in PHD-SR COVID-19. ICU admission was the easiest outcome to predict (best AUC=79%), and HS was the hardest to predict (best AUC=70%). Models performed similarly within each outcome.DiscussionAlthough the models learned to attend to meaningful clinical information, they performed similarly, suggesting performance limitations are inherent to the data.ConclusionPredictive models using raw EMR data are promising because they can use many observations and encompass a large feature space; however, traditional and deep learning models may perform similarly when few features are available at the individual patient level.
In macrophages fatty acid oxidation spares glutamate for use in diverse metabolic pathways required for alternative activation
Authors: van Teijlingen Bakker Nikki , Flachsman Lea , Carrizo Gustavo E. , Sanin David E. , Lawless Simon , Castoldi Angela , Monteiro Lauar , Kabat Agnieszka M. , Matsushita Mai , Haessler Fabian , Patterson Annette , Geltink Ramon Klein , O’Sullivan David , Pearce Erika L. , Pearce Edward J. 
Published: April 2022

AbstractFatty acid oxidation (FAO) is upregulated in IL-4-stimulated (alternatively activated) macrophages (M(IL-4)). We examined the effect of loss of function of the enzyme Cpt1a, which facilitates the entry of long chain fatty acids (FA) into mitochondria for FAO, on alternative activation. Expression of M(IL-4) markers ARG1, CD301 and RELMα, was impaired in tamoxifen-treated ERT2Cre x Cpt1afl/fl macrophages and in macrophages expressing shRNA targeting Cpt1a (Cpt1a-shRNA). In contrast, VaviCre x Cpt1afl/fl and LysmCre x Cpt1afl/fl M(IL-4) responded normally to IL-4. Reduced alternative activation due to Cpt1a loss of function was linked to decreased cellular pools of α-ketoglutarate, glutamate, and glutathione, diminished commitment of glucose carbon to serine/glycine synthesis, and decreased expression of genes in the Nrf2-oxidative stress response pathway. Consistent with this, reactive oxygen species were increased. Restoration of glutathione pools with N-acetyl cysteine normalized oxidative stress and allowed alternative activation in the face of Cpt1a-deficiency, pointing to a role for FAO in the control of ROS and as being important for alternative activation. In VaviCre x Cpt1afl/fl M(IL-4), glutamine uptake was increased, compensating for the loss of FAO to meet necessary metabolic demands, to allow alternative activation. The data indicate that macrophages are able to regulate glutamine metabolism to compensate for chronic disruption of FAO to meet metabolic needs.
Profiling the size-dependent heterogeneity of membrane proteins in a mixed population of small extracellular vesicle for potential cancer diagnosis
Authors: Zhai Chunhui , Xie Feng , Zeng Qiang , Zheng Weiqiang , Wang Jingan , Hu Haiyan , Yang Yuting , Ding Xianting , Yu Hui 
Published: April 2022

AbstractThe heterogeneity in small extracellular vesicles (small EVs) introduces an extra level of complexity in small EV-based liquid biopsy for cancer diagnosis. Heterogeneous membrane protein expression is correlated with sizes of small EVs, but accessing this correlative information is limited by the precise isolation of size-dependent subpopulations. Herein, we present a single EV enumeration (SEVEN) approach to profile protein heterogeneity in size-dependent subpopulations, and demonstrate its potential in improving the accuracy of cancer diagnosis. The interferometric plasmonic microscopy (iPM) capable of imaging single biological nanoparticles with the diameter down to 30 nm is employed to detect small EVs at the single-particle level. Small EVs population with mixed sizes are directly imaged, individually sized and digitally counted during their binding onto different aptamer-coated iPM sensor surfaces. The protein expression levels and binding kinetics of three size-dependent subpopulations are analyzed, forming a multidimensional data matrix for cancer diagnosis. Using small EVs derived from different cancer cell lines, highly heterogeneous protein profiles are recorded in the three subpopulations. We further demonstrate that the cancer classification accuracy could be greatly improved by including the subpopulation level heterogeneous protein profiles as compared with conventional ensemble measurement.
Innovations in freight transport: a systematic literature evaluation and COVID implications
Authors: Kiani Mavi Reza , Kiani Mavi Neda , Olaru Doina , Biermann Sharon , Chi Sae 
Published: April 2022

PurposeThis paper systematically evaluates the existing literature of innovations in freight transport, including all modes, to uncover the key research themes and methodologies employed by researchers to study innovations and their implications in this industry. It analyses the role of transport and the impact of innovations during crises, such as COVID-19.Design/methodology/approachQualitative and quantitative analysis of the innovations in freight transport unravels the pre-requisites of such endeavours in achieving a resilient and sustainable transport network that effectively and efficiently operates during a crisis. The authors performed keyword co-occurrence network (KCON) analysis and research focus parallelship network (RFPN) analysis using BibExcel and Gephi to determine the major resulting research streams in freight transport.FindingsThe RFPN identified five emerging themes: transport operations, technological innovation, transport economics, transport policy and resilience and disaster management. Optimisation and simulation techniques, and more recently, artificial intelligence and machine learning (ML) approaches, have been used to model and solve freight transport problems. Automation innovations have also penetrated freight and supply chains. Information and communication technology (ICT)-based innovations have also been found to be effective in building resilient supply chains.Research limitations/implicationsGiven the growth of e-commerce during COVID-19 and the resulting logistics demand, along with the need for transporting food and medical emergency products, the role of automation, optimisation, monitoring systems and risk management in the transport industry has become more salient. Transport companies need to improve their operational efficiency using innovative technologies and data science for informed decision-making.Originality/valueThis paper advises researchers and practitioners involved in freight transport and innovation about main directions and gaps in the field through an integrated approach for evaluating research undertaken in the area. This paper also highlights the role of crisis, e.g. COVID-19, and its impacts on freight transport. Major contributions of this paper are as follows: (1) a qualitative and quantitative, systematic and effective assessment of the literature on freight transport through a network analysis of keywords supplemented by a review of the text of 148 papers; (2) unravelling major research areas; (3) identifying innovations in freight transport and their classification as technological and non-technological and (4) investigating the impact of crises and disruptions in freight transport.
On the differential response of loans to shocks in the USA
Authors: Cafiso Gianluca 
Published: April 2022

PurposeThe purpose of this paper is to gain insights useful to explain the loan puzzle: the unexpected increase of loans to firms in case of a monetary tightening. To this end, the authors develop the analysis using several loan categories distinguished by lender, scope and borrower. This approach helps to unveil significant differences on how those categories respond to the same shock and allow to evaluate possible alternative explanations for such differences.Design/methodology/approachThe paper is empirical. The analysis is based on a large vector auto-regression, estimated using Bayesian techniques and has as object the US economy.FindingsThe findings support a supply-side explanation of the loan puzzle, i.e. banks reshuffle their portfolio in favor of short-term business loans after a monetary tightening. Moreover, the authors achieve the following results. First, the analysis shows that loans to small firms increase as well, but less than what observed with large firms: small firms stay between large firms and households. Second, considering advances and other loans allows to conclude that finance companies behave very much as banks. Third, some limited evidence suggests that not just industrial and commercial loans to firms might increase but also more long-term loans, such as mortgages.Originality/valueThe authors develop an analysis, based on state-of-the-art Bayesian techniques, that reveals the differential response of well-distinguished loan categories to several shocks; monetary and real shocks in the first place. After showing their heterogenous response, the authors discuss it in detail, with specific reference to supply and demand factors of credit intrinsic to the transmission mechanism. With respect to previous contributions, the authors consider a plurality of loan categories functional to understand the reason behind each specific response. This allows to conclude in favor of supply factors as an explanation of the unexpected increase of loans to corporate firms in case of a monetary shock.
Integral representation method based efficient rule optimizing framework for anti-money laundering
Authors: Badics Tamás , Hajtó Dániel , Tornai Kálmán , Kiss Levente , Reguly István Zoltán , Pesti István , Sváb Péter , Cserey György 
Published: April 2022

Purpose
This paper aims to introduce a framework for optimizing rule-based anti-money laundering systems with a clear economic interpretation, and the authors introduce the integral representation method.

Design/methodology/approach
By using a microeconomic model, the authors reformulate the threshold optimization problem as a decision problem to gain insights from economics regarding the main properties of the optimum. The authors used algorithmic considerations to find an efficient implementation by using a kind of weak mode estimate of the distribution and the authors extend this approach to classes of alerts or cases.

Findings
The method provides a new and efficient alternative for the sampling method or the multidimensional optimization technique described in the literature to decrease the bias emanating from multiple alerts by smoothing the number of alerts across classes in the optimum and decrease the overlapping between scenarios at the case level. Using the method for real bank data, the authors were able to decrease the number of false positives cases by about 18% while retaining almost 98% of the true-positive cases.

Research limitations/implications
The model assumes that alerts from different scenarios are indifferent to the bank. To include scenario-specific preferences or constraints demands further research.

Originality/value
The new framework presented in the paper is a flexible extension of the usual above-the-line method, which makes it possible to include bank preferences and use the parallelization capabilities of modern processors.