bluuebunny/crossref_metadata_2025_split huggingface dataset:
Systemic Opioid Prescribing Patterns and Total Cost of Care in Patients Initiating Spinal Cord Stimulation Therapy: A Retrospective Analysis
Authors: Fraifeld Eduardo M , Hatheway John A , Ricker Christine N 
Published: January 2021

Abstract

Background
Few studies have evaluated patterns of systemic opioid use among patients initiating spinal cord stimulation therapy for chronic pain. This study evaluated systemic opioid discontinuation and/or dose reduction and total health care cost after the start of spinal cord stimulation therapy.

Methods
Using a commercial insurance claims database (2008–2017), we analyzed opioid utilization patterns in patients initiating spinal cord stimulation therapy over a 1-year baseline and 2-year follow-up. The primary end point was defined as either discontinuation (≥365-day gap between prescription fills or total days’ supply in follow-up ≤30 days) or ≥50% reduction in average daily morphine milligram equivalent dose. “Costs” were defined as total payer plus patient out-of-pocket payments.

Results
A total of 5,878 patients met the selection criteria. Of these, 152 (2.6%) showed no opioid prescription data at any point in the study period. Among patients with one or more prescriptions, 42.0% met the primary end point (22.0% discontinued, and 20.0% reduced their dose by 50% or more). Mean total adjusted costs were significantly reduced in years 1 and 2 of follow-up relative to baseline (excluding device insertion costs). The average time to breakeven when accounting for device trial and permanent insertion cost was 3.1 years among those who met the composite end point and 4.2 years among those who did not.

Conclusions
This analysis shows that among patients who continued spinal cord stimulation therapy for at least 2 years, a significant proportion were able to reduce and/or discontinue systemic opioid use, with costs after the start of therapy significantly reduced relative to baseline.
The Index Theorem for Toeplitz Operators as a Corollary of Bott Periodicity
Authors: Baum Paul F , Van Erp Erik 
Published: January 2021

Abstract
This is an expository paper about the index of Toeplitz operators, and in particular Boutet de Monvel’s theorem [5]. We prove Boutet de Monvel’s theorem as a corollary of Bott periodicity, and independently of the Atiyah-Singer index theorem.
Peripheral ulcerative keratitis in rheumatoid arthritis patients taking tocilizumab: paradoxical manifestation or insufficient efficacy?
Authors: Cohen Florian , Gabison Eric Ernest , Stéphan Sophie , Belkhir Rakiba , Nocturne Gaetane , Best Anne-Laurence , Haigh Oscar , Barreau Emmanuel , Labetoulle Marc , Seror Raphaele , Rousseau Antoine 
Published: January 2021

Abstract

Objectives
Peripheral ulcerative keratitis (PUK) is a severe corneal condition associated with uncontrolled RA. Tocilizumab (TCZ) is used to control RA, however, episodes of paradoxical ocular inflammation have been reported in TCZ-treated patients. We report a case series of PUK in TCZ-treated RA patients with ophthalmological and systemic findings and discuss the potential underlying mechanisms.

Methods
Four patients (six eyes), 47–62 years of age, were included. At the onset of PUK, the median duration of RA was 13 years [interquartile range (IQR) 3–13] and the median treatment with TCZ was 9 months (IQR 3–14). Two patients had active disease [28-joint DAS (DAS28) &gt;3.2] and the disease was controlled in two patients (DAS28 ≤3.2).

Results
TCZ was initially replaced by another immunomodulatory treatment in all patients and later reintroduced in two patients without PUK recurrence. Corneal inflammation was controlled in all cases with local and systemic treatments, with severe visual loss in one eye.

Conclusion
PUK may occur in patients with long-standing RA after a switch to TCZ and can be interpreted, depending on the context, as insufficient efficacy or a paradoxical manifestation. These cases highlight the urgent need for reliable biomarkers of the efficacy and paradoxical reactions of biologics.
A Method for Tapering Antipsychotic Treatment That May Minimize the Risk of Relapse
Authors: Horowitz Mark Abie , Jauhar Sameer , Natesan Sridhar , Murray Robin M , Taylor David 
Published: January 2021

Abstract
The process of stopping antipsychotics may be causally related to relapse, potentially linked to neuroadaptations that persist after cessation, including dopaminergic hypersensitivity. Therefore, the risk of relapse on cessation of antipsychotics may be minimized by more gradual tapering. There is converging evidence that suggests that adaptations to antipsychotic exposure can persist for months or years after stopping the medication—from animal studies, observation of tardive dyskinesia in patients, and the clustering of relapses in this time period after the cessation of antipsychotics. Furthermore, PET imaging demonstrates a hyperbolic relationship between doses of antipsychotic and D2 receptor blockade. We, therefore, suggest that when antipsychotics are reduced, it should be done gradually (over months or years) and in a hyperbolic manner (to reduce D2 blockade “evenly”): ie, reducing by one quarter (or one half) of the most recent dose of antipsychotic, equivalent approximately to a reduction of 5 (or 10) percentage points of its D2 blockade, sequentially (so that reductions become smaller and smaller in size as total dose decreases), at intervals of 3–6 months, titrated to individual tolerance. Some patients may prefer to taper at 10% or less of their most recent dose each month. This process might allow underlying adaptations time to resolve, possibly reducing the risk of relapse on discontinuation. Final doses before complete cessation may need to be as small as 1/40th a therapeutic dose to prevent a large decrease in D2 blockade when stopped. This proposal should be tested in randomized controlled trials.
Neural Processing of Repeated Emotional Scenes in Schizophrenia, Schizoaffective Disorder, and Bipolar Disorder
Authors: Trotti Rebekah L , Abdelmageed Sunny , Parker David A , Sabatinelli Dean , Tamminga Carol A , Gershon Elliot S , Keedy Sarah K , Keshavan Matcheri S , Pearlson Godfrey D , Sweeney John A , McDowell Jennifer E , Clementz Brett A 
Published: January 2021

Abstract
Impaired emotional processing and cognitive functioning are common in schizophrenia, schizoaffective disorder, and bipolar disorders, causing significant socioemotional disability. While a large body of research demonstrates abnormal cognition/emotion interactions in these disorders, previous studies investigating abnormalities in the emotional scene response using event-related potentials (ERPs) have yielded mixed findings, and few studies compare findings across psychiatric diagnoses. The current study investigates the effects of emotion and repetition on ERPs in a large, well-characterized sample of participants with schizophrenia-bipolar syndromes. Two ERP components that are modulated by emotional content and scene repetition, the early posterior negativity (EPN) and late positive potential (LPP), were recorded in healthy controls and participants with schizophrenia, schizoaffective disorder, bipolar disorder with psychosis, and bipolar disorder without psychosis. Effects of emotion and repetition were compared across groups. Results displayed significant but small effects in schizophrenia and schizoaffective disorder, with diminished EPN amplitudes to neutral and novel scenes, reduced LPP amplitudes to emotional scenes, and attenuated effects of scene repetition. Despite significant findings, small effect sizes indicate that emotional scene processing is predominantly intact in these disorders. Multivariate analyses indicate that these mild ERP abnormalities are related to cognition, psychosocial functioning, and psychosis severity. This relationship suggests that impaired cognition, rather than diagnosis or mood disturbance, may underlie disrupted neural scene processing in schizophrenia-bipolar syndromes.
Effects of sleep restriction on the sleep electroencephalogram of adolescents
Authors: Campbell Ian G , Cruz-Basilio Alejandro , Darchia Nato , Zhang Zoey Y , Feinberg Irwin 
Published: January 2021

Abstract

Study Objectives
This report describes findings from an ongoing longitudinal study of the effects of varied sleep durations on wake and sleep electroencephalogram (EEG) and daytime function in adolescents. Here, we focus on the effects of age and time in bed (TIB) on total sleep time (TST) and nonrapid eye movement (NREM) and rapid eye movement (REM) EEG.

Methods
We studied 77 participants (41 male) ranging in age from 9.9 to 16.2 years over the 3 years of this study. Each year, participants adhered to each of three different sleep schedules: four consecutive nights of 7, 8.5, or 10 h TIB.

Results
Altering TIB successfully modified TST, which averaged 406, 472 and 530 min on the fourth night of 7, 8.5, and 10 h TIB, respectively. As predicted by homeostatic models, shorter sleep durations produced higher delta power in both NREM and REM although these effects were small. Restricted sleep more substantially reduced alpha power in both NREM and REM sleep. In NREM but not REM sleep, sleep restriction strongly reduced both the all-night accumulation of sigma EEG activity (11–15 Hz energy) and the rate of sigma production (11–15 Hz power).

Conclusions
The EEG changes in response to TIB reduction are evidence of insufficient sleep recovery. The decrease in sigma activity presumably reflects depressed sleep spindle activity and suggests a manner by which sleep restriction reduces waking cognitive function in adolescents. Our results thus far demonstrate that relatively modest TIB manipulations provide a useful tool for investigating adolescent sleep biology.
Effects of moderate sleep restriction during 8-week calorie restriction on lipoprotein particles and glucose metabolism
Authors: Sparks Joshua R , Porter Ryan R , Youngstedt Shawn D , Bowyer Kimberly P , Durstine J Larry , Wang Xuewen 
Published: January 2021

AbstractStudy ObjectivesThis study examined how glucose, glucose regulatory hormones, insulin sensitivity, and lipoprotein subclass particle concentrations and sizes change with sleep restriction during weight loss elicited by calorie restriction.MethodsOverweight or obese adults were randomized into an 8-week calorie restriction intervention alone (CR, n = 12; 75% female; body mass index = 31.4 ± 2.9 kg/m2) or combined with sleep restriction (CR+SR, n = 16; 75% female; body mass index = 34.5 ± 3.1 kg/m2). Participants in both groups were given the same instructions to reduce calorie intake. Those in the CR+SR group were instructed to reduce their habitual time-in-bed by 30–90 minutes 5 days each week with 2 ad libitum sleep days. Fasting venous blood samples were collected at pre- and post-intervention.ResultsDifferential changes were found between the two groups (p = 0.028 for group × time interaction) in glucagon concentration, which decreased in the CR group (p = 0.016) but did not change in CR+SR group. Although changes in mean HDL particle (HDL-P) size and visfatin concentration were not statistically different between groups (p = 0.066 and 0.066 for group×time interaction, respectively), mean HDL-P size decreased only in the CR+SR group (Cohen’s d = 0.50, p = 0.022); visfatin concentrations did not change significantly in either group but appeared to decrease in the CR group (Cohen’s d = 0.67, p = 0.170) but not in the CR+SR group (Cohen’s d = 0.43, p = 0.225).ConclusionThese results suggest that moderate sleep restriction, despite the presence of periodic ad libitum sleep, influences lipoprotein subclass particles and glucose regulation in individuals undergoing calorie restriction.Clinical trial registration: ClinicalTrials.gov (NCT02413866, Weight Outlooks by Restriction of Diet and Sleep)
The role of reproductive loss on flock performance: a comparison of nine industry flocks
Authors: Shorten Paul R , Edwards Sara J , Juengel Jenny L 
Published: January 2021

AbstractThe reproductive performance of a sheep flock is dependent on a multitude of complex interacting factors. Attaining optimal flock performance requires information about how the reproductive steps are linked and relate to readily available measurements of the state of the flock. The goal was to use data from nine commercial flocks (greater than 300,000 records) to investigate and model the key reproductive steps affecting flock reproductive performance. We also developed a maximum-likelihood based methodology to predict flock ovulation rate based on measurements of the number of fetuses at mid-pregnancy (detected by ultrasound-scanning). The model was used to determine how changes in premating liveweight, age, predicted ovulation rate, number of fetuses at mid-pregnancy, lamb survival and lamb growth rate affect the total lamb liveweight at weaning per ewe exposed to the ram in each flock. The data from the commercial flocks were also used to investigate the role of ewe age and premating liveweight on each reproductive step. Sensitivity analyses were conducted to identify the key reproductive steps affecting flock reproductive performance, with a focus on understanding how these steps vary between flocks. The elasticity for embryo survival was 60% of that for lamb survival for these flocks and the elasticities for ovulation rate were highly variable between flocks (0.16 to 0.50 for mature ewes). This indicates that ovulation rate was near-optimal for some flocks, whereas there was potential to significantly improve flock performance in suboptimal flocks. The elasticity for ewe premating liveweight was highly variable between flocks (−0.03 to 0.84 for mature ewes and −0.18 to 1.39 for ewe lambs), indicating that premating liveweight ranged from optimal to suboptimal between flocks. For these suboptimal farms, the opportunity exists to increase flock performance through improved management of ewe premating liveweight. Reproductive loss was significantly greater in ewe lambs than mature ewes, although the difference is dependent on the stage of reproduction and flock. Predicted ovulation rate was 25% lower for ewe lambs and there was a 30% relative decrease in the predicted embryo survival probability from ovulation to scanning for ewe lambs. There was a 10% relative decrease in lamb survival probability from birth to weaning for ewe lambs and lamb growth rate was 25% lower for ewe lambs.
Ending the ‘Cult of the Broken Home’: Divorce, Children and the Changing Emotional Dynamics of Separating British Families, c. 1945–90
Authors: Miller Ian 
Published: January 2021

Abstract
From the 1960s, rising divorce rates forced a re-thinking of family dynamics beyond the nuclear. Traditionally, experts and the public had presumed that children from ‘broken homes’ typically drifted into juvenile delinquency and crime. Children of divorce were blamed for a plethora of social problems. The increasingly common nature of divorce meant that this model was no longer sustainable. Post-war children of divorce were more likely to be framed as ‘emotionally vulnerable’ and studied in more nuanced ways, not least because it seemed increasingly obvious that not all affected children grew up delinquent. However, a new consensus emerged that problems could only be avoided if parents created appropriate emotional conditions while separating and divorcing, and if parents and children openly communicated their feelings throughout the process. Children themselves were actively encouraged, through a new genre of divorce manuals often aimed at them, to express their emotions with parents and friends. Using Britain as a case study, this article argues that emotions became central to discussion of divorce in the post-war period, placing onuses on breaking down families to create a positive emotional space for affected children.
High-Throughput Transcriptomics Platform for Screening Environmental Chemicals
Authors: Harrill Joshua A , Everett Logan J , Haggard Derik E , Sheffield Thomas , Bundy Joseph L , Willis Clinton M , Thomas Russell S , Shah Imran , Judson Richard S 
Published: January 2021

AbstractNew approach methodologies (NAMs) that efficiently provide information about chemical hazard without using whole animals are needed to accelerate the pace of chemical risk assessments. Technological advancements in gene expression assays have made in vitro high-throughput transcriptomics (HTTr) a feasible option for NAMs-based hazard characterization of environmental chemicals. In this study, we evaluated the Templated Oligo with Sequencing Readout (TempO-Seq) assay for HTTr concentration-response screening of a small set of chemicals in the human-derived MCF7 cell model. Our experimental design included a variety of reference samples and reference chemical treatments in order to objectively evaluate TempO-Seq assay performance. To facilitate analysis of these data, we developed a robust and scalable bioinformatics pipeline using open-source tools. We also developed a novel gene expression signature-based concentration-response modeling approach and compared the results to a previously implemented workflow for concentration-response analysis of transcriptomics data using BMDExpress. Analysis of reference samples and reference chemical treatments demonstrated highly reproducible differential gene expression signatures. In addition, we found that aggregating signals from individual genes into gene signatures prior to concentration-response modeling yielded in vitro transcriptional biological pathway altering concentrations (BPACs) that were closely aligned with previous ToxCast high-throughput screening assays. Often these identified signatures were associated with the known molecular target of the chemicals in our test set as the most sensitive components of the overall transcriptional response. This work has resulted in a novel and scalable in vitro HTTr workflow that is suitable for high-throughput hazard evaluation of environmental chemicals.
Genome Sequence Data of Peronophythora litchii, an Oomycete Pathogen Causing Litchi Downy Blight
Authors: Guo Hengyuan , Bao Jiandong , Lin Lianyu , Wang Zhixin , Shi Mingyue , Huang Yuting , Wang Rongbo , Li Benjin , Liu Peiqing , Chen Qinghe 
Published: January 2021

Peronophythora litchii is an oomycete pathogen that exclusively infects litchi, with infection stages affecting a broad range of tissues. In this study, we obtained a near chromosome-level genome assembly of P. litchii ZL2018 from China using Oxford Nanopore Technologies long-read sequencing and Illumina short-read sequencing. The genome assembly was 64.15 Mb in size and consisted of 81 contigs with an N50 of 1.43 Mb and a maximum length of 4.74 Mb. Excluding 34.67% of repeat sequences, 14,857 protein-coding genes were identified, among which 14,447 genes were annotated. We also predicted 306 candidate RxLR effectors in the assembly. The high-quality genome assembly and annotation resources reported in this study will provide new insight into the infection mechanisms of P. litchii. [Formula: see text] The author(s) have dedicated the work to the public domain under the Creative Commons CC0 “No Rights Reserved” license by waiving all of his or her rights to the work worldwide under copyright law, including all related and neighboring rights, to the extent allowed by law. 2021
Management of Ralstonia solanacearum in Tomato Using ZnO Nanoparticles Synthesized Through Matricaria chamomilla
Authors: Khan Raja Asad Ali , Tang Yuanyang , Naz Ishrat , Alam Syed Sartaj , Wang Wenzhao , Ahmad Musharaf , Najeeb Saba , Rao Crist , Li Yanlin , Xie Bingyan , Li Yan 
Published: January 2021

Matricaria chamomilla flower extract was used as a biocompatible material for synthesis of zinc oxide nanoparticles (ZnONPs). The synthesized NPs were evaluated for their antibacterial potential in vitro and in vivo against the Gram-negative bacterium Ralstonia solanacearum, which causes devastating bacterial wilt disease in tomato and other crops. Synthesized ZnONPs were further analyzed by UV-visible spectroscopy, Fourier transform infrared spectroscopy, x-ray diffraction, transmission electron microscopy, and scanning electron microscopy with energy-dispersive spectroscopy. The synthesized polydisperse ZnONPs were found to be in the size range of 8.9 to 32.6 nm, and at 18.0 µg ml−1 exhibited maximum in vitro growth inhibition of the pathogen R. solanacearum. Scanning electron microscopy analysis of affected bacterial cells showed morphological deformation such as disruption of the cell membrane and wall, and the leakage of cell contents. Results of in vivo studies also showed that application of ZnONPs to the artificially inoculated tomato plants with the pathogen R. solanacearum significantly enhanced the plant growth by reducing bacterial soil population and disease severity as compared with the untreated control. Biosynthesized ZnONPs could be an effective approach to control the bacterium R. solanacearum.
Effect of Ozone on Inactivation of Purified Pepper Mild Mottle Virus and Contaminated Pepper Seed
Authors: Stommel John R. , Dumm Judith M. , Hammond John 
Published: January 2021

Pepper mild mottle virus (PMMoV) is a major viral pathogen of pepper (Capsicum spp.). PMMoV is readily mechanically transmitted and is seed transmissible. Trisodium phosphate (TSP) treatment is commonly used to reduce the level of viable PMMoV in contaminated seed. Ozone is efficacious in disinfecting fungal-contaminated seed and disrupting bacterial and viral pathogens on various substrates. The purpose of this study was to evaluate efficacy of ozone and chemical treatment on PMMoV viability. Treated pepper seed infectivity was evaluated via bioassay with Nicotiana benthamiana. Symptoms of PMMoV infection were not observed in bioassays of TSP-treated seed. Sufficient viable PMMoV remained on ozone-treated seed to cause infection, which was confirmed by ELISA. Neither treatment affected seed germination. Ozone treatment of purified PMMoV was assessed to determine the extent, if any, of PMMoV inactivation by ozone. At the low PMMoV concentration (0.01 mg/ml), 14-h ozone exposure eliminated infectivity as determined by N. benthamiana bioassays with ELISA confirmations. At the higher PMMoV concentration (0.1 mg/ml), ozone treatment was insufficient to prevent infection. Ozone inactivation of purified PMMoV was quantified via bioassay using the local lesion host N. glutinosa and quantitative real-time PCR. Ozone exposure reduced lesion counts and PMMoV concentration, and PMMoV degradation increased with exposure time. Although PMMoV infection was eliminated at the low PMMoV concentration, bioassays using naturally infected seed and purified PMMoV preparations at relatively higher concentrations demonstrated that ozone is not efficacious as a standard treatment to sufficiently reduce levels of infective PMMoV in contaminated pepper seed. [Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Clinical Validation of a Proteomic Biomarker Threshold for Increased Risk of Spontaneous Preterm Birth
Authors: Burchard Julja , Polpitiya Ashoka D. , Fox Angela C. , Randolph Todd , Fleischer Tracey C. , Dufford Max , Garite Thomas J. , Critchfield Greg C. , Boniface J. Jay , Kearney Paul E. 
Published: January 2021

AbstractPreterm births are prevalent and a leading cause of neonatal death in the United States. Despite the availability of effective interventions, to date there is not a robust and widely applicable test to identify pregnancies at high risk for spontaneous preterm birth (sPTB). Previously, a sPTB predictor based on the ratio of two proteins, IBP4/SHBG, was validated as an accurate predictor of sPTB in the observational study Proteomic Assessment of Preterm Risk (PAPR). Here it is demonstrated that the same predictor threshold associated with 2-fold increased risk of sPTB, namely −1.4, is also statistically significant for predicting elevated risk of sPTB in the observational study Multicenter Assessment of a Spontaneous Preterm Birth Risk Predictor (TreeToP).