bluuebunny/crossref_metadata_2025_split huggingface dataset:
A case of clinically amyopathic dermatomyositis that was refractory to intensive immunosuppressive therapy including tofacitinib, but successfully treated with plasma exchange therapy
Authors: Hiraoka Daisuke , Ishizaki Jun , Horie Kenta , Matsumoto Takuya , Suemori Koichiro , Takenaka Katsuto , Hasegawa Hitoshi 
Published: January 2022

ABSTRACT
Clinically amyopathic dermatomyositis (CADM) patients often develop rapidly progressive interstitial lung disease (RP-ILD). A high level of anti-melanoma differentiation-associated gene 5 antibodies (anti-MDA5 Ab) before treatment is associated with RP-ILD development, a poor treatment response, and poor survival. The prognosis of CADM patients remains poor due to ILD even with combined intensive immunosuppressive therapy. Recently, several additional therapies, including tofacitinib (TOF) and plasma exchange (PE) therapy, have been reported to be effective. We herein report a case of CADM-ILD with a high level of anti-MDA5 Ab that was refractory to combined intensive immunosuppressive therapy including TOF, but successfully treated with PE. The following are possible reasons why TOF was ineffective: (1) cytokines that were not suppressed by TOF played an important role in RP-ILD; (2) TOF was administered later than previously reported; and (3) TOF did not suppress pathological substances such as antibodies. On the other hand, PE removes cytokines and various pathological substances. Therefore, PE may be a more reasonable additional therapy for intractable CADM-ILD.
A population study of clinical trial accrual for women and minorities in neuro-oncology following the NIH Revitalization Act
Authors: Reihl Sheantel J , Patil Nirav , Morshed Ramin A , Mehari Mulki , Aabedi Alexander , Chukwueke Ugonma N , Porter Alyx B , Fontil Valy , Cioffi Gino , Waite Kristin , Kruchko Carol , Ostrom Quinn , Barnholtz-Sloan Jill , Hervey-Jumper Shawn L 
Published: January 2022

Abstract

Background
The NIH Revitalization Act, implemented 29 years ago, set to improve the representation of women and minorities in clinical trials. In this study, we investigate progress made in all phase therapeutic clinical trials for neuroepithelial CNS tumors stratified by demographic-specific age-adjusted disease incidence and mortality. Additionally, we identify workforce characteristics associated with clinical trials meeting established accrual benchmarks.

Methods
Registry study of published clinical trials for World Health Organization defined neuroepithelial CNS tumors between January 2000 and December 2019. Study participants were obtained from PubMed and ClinicalTrials.gov. Population-based data originated from the CBTRUS for incidence analyses. SEER-18 Incidence-Based Mortality data was used for mortality analysis. Descriptive statistics, Fisher exact, and χ 2 tests were used for data analysis.

Results
Among 662 published clinical trials representing 49 907 participants, 62.5% of participants were men and 37.5% women (P &lt; .0001) representing a mortality specific over-accrual for men (P = .001). Whites, Asians, Blacks, and Hispanics represented 91.7%, 1.5%, 2.6%, and 1.7% of trial participants. Compared with mortality, Blacks (47% of expected mortality, P = .008), Hispanics (17% of expected mortality, P &lt; .001) and Asians (33% of expected mortality, P &lt; .001) were underrepresented compared with Whites (114% of expected mortality, P &lt; .001). Clinical trials meeting accrual benchmarks for race included minority authorship.

Conclusions
Following the Revitalization Act, minorities and women remain underrepresented in therapeutic clinical trials for neuroepithelial tumors, relative to disease incidence and mortality. Study accrual has improved with time. This study provides a framework for clinical trial accrual efforts and offers guidance regarding workforce considerations associated with enrollment of underserved patients.
The Mood Boost from Tobacco Cigarettes is More Erratic with the Additions of Cannabis and Alcohol
Authors: Kendall Ashley D , Hedeker Donald , Diviak Kathleen R , Mermelstein Robin J 
Published: January 2022

Abstract

Introduction
A large body of literature indicates that nicotine results in an acute mood “boost,” including increased positive affect and decreased negative affect. Young adults frequently engage in polysubstance use of cigarettes with cannabis and alcohol—a trend that is likely to accelerate with the expanding legalization of cannabis. However, little is known about whether polysubstance use, defined here as combustible tobacco cigarette use within the same hour as cannabis and alcohol, is associated with changes in the nicotine mood boost. The present study aimed to address this gap.

Methods
Young adults (N = 202, 52% female, mean age = 21 years at time 1) provided ecological moments assessment (EMA) reports of cigarette use over two 7-day bursts spaced 1 year apart. In each report, participants rated mood levels before and after smoking, and indicated cannabis and alcohol use. Mixed-effects location-scale modeling simultaneously tested changes in mood levels and variability related to smoking events with cannabis and/or alcohol compared with smoking-only events.

Results
From before to after smoking, positive affect increased and negative affect decreased, on average. Overall, the additions of cannabis and/or alcohol had nonsignificant associations with these mean changes. However, polysubstance use, as well as cigarette-cannabis co-use, were each associated with significantly greater within-person variability in the positive and negative affect changes related to smoking.

Conclusions
The mood benefits associated with smoking were more erratic in the contexts of polysubstance use and cigarette-cannabis co-use. Potential implications for young adults’ long-term nicotine use trajectories are discussed.

Implications
Among young adults who smoke cigarettes, the mood “boost” from smoking may be more erratic—which is to say, more likely to be either amplified or attenuated—with the additions of cannabis and alcohol together, or cannabis alone. On occasions when young adults seek out cannabis and alcohol to enhance their smoking mood boost, but instead experience a dampening effect, they might consume more nicotine, contributing over time to greater dependence. Future investigation is warranted, with particular attention to nicotine-cannabis co-use.
Treatment Patterns, Health Care Resource Utilization, and Cost in Patients with Myelofibrosis in the United States
Authors: Copher Ronda , Kee Arianna , Gerds Aaron 
Published: January 2022

Abstract

Background
This study analyses treatment patterns, health care resource utilization (HCRU), and costs in patients with myelofibrosis (MF) and a subgroup treated with ruxolitinib (RUX).

Materials and Methods
Treatment patterns, all-cause and MF-related HCRU, and costs were analyzed in adults with MF with continuous enrollment in a commercial or the Medicare Advantage health plan in the pre-index period, defined as the 12 months immediately prior to the index date (date of primary or secondary MF diagnosis), and the post-index period, defined as ≥6 months following the index date. In a subgroup analysis, outcomes were analyzed in patients treated with optimal RUX (OPT RUX, ≥30 mg) and suboptimal RUX (SUB RUX, &lt;30 mg) in the pre-index RUX period, defined as the 3 months immediately prior to the index RUX date (first date for an RUX claim), and the post-index RUX period, defined as ≥6 months following the index RUX date.

Results
Of 2830 patients with an MF diagnosis, 1191 met eligibility requirements. The median age of patients was 72 years, 54% were male, and comorbidities were frequent. Sixty percent of patients received ≥1 line of therapy (LOT), of which 46% (n = 331) had ≥2 LOTs during the post-index MF period. Costs increased considerably 6-month pre-index to 6-month post-index (all-cause: cause ($24,216 to $48,966) and MF-related ($16,502 to $39,383), driven by inpatient stays and pharmacy costs. In the subgroup analysis, patients treated with RUX (n = 495) experienced significant disease burden and high costs, regardless of dose. A shorter duration of therapy and a higher rate of discontinuation were observed in patients treated with SUB RUX (n = 191) versus OPT RUX (n = 304).

Conclusion
These findings suggest a significant disease and economic impacts associated with MF patients that persists with RUX therapy, highlighting the need for additional therapeutic options for MF.
The Role of Triacylglycerol in the Protection of Cells against Lipotoxicity under Drought in Lolium multiflorum/Festuca
arundinacea Introgression Forms
Authors: Perlikowski Dawid , Lechowicz Katarzyna , Skirycz Aleksandra , Michaelis Änna , Pawłowicz Izabela , Kosmala Arkadiusz 
Published: January 2022

Abstract
Triacylglycerol is a key lipid compound involved in maintaining homeostasis of both membrane lipids and free fatty acids (FFA) in plant cells under adverse environmental conditions. However, its role in the process of lipid remodeling has not been fully recognized, especially in monocots, including grass species. For our study, two closely related introgression forms of Lolium multiflorum (Italian ryegrass) and Festuca arundinacea (tall fescue), distinct in their level of drought tolerance, were selected as plant models to study rearrangements in plant lipidome under water deficit and further re-watering. The low drought tolerant (LDT) form revealed an elevated level of cellular membrane damage accompanied by an increased content of polyunsaturated FFA and triacylglycerol under water deficit, compared with the high drought tolerant (HDT) form. However, the LDT introgression form demonstrated also the ability to regenerate its membranes after stress cessation. The obtained results clearly indicated that accumulation of triacylglycerol under advanced drought in the LDT form could serve as a cellular protective mechanism against overaccumulation of toxic polyunsaturated FFA and other lipid intermediates. Furthermore, accumulation of triacylglycerol under drought conditions could serve also as storage of substrates required for further regeneration of membranes after stress cessation. The rearrangements in triacylglycerol metabolism were supported by the upregulation of several genes, involved in a biosynthesis of triacylglycerol. With respect to this process, diacylglycerol O-acyltransferase DGAT2 seems to play the most important role in the analyzed grasses.
Optimal Capital Structure with Imperfect Competition
Authors: Matveyev Egor , Zhdanov Alexei 
Published: January 2022

Abstract
We develop a model of optimal capital structure in imperfectly competitive markets by focusing on a duopoly. The model endogenizes both the financing and investment decisions of firms. We show that in equilibrium the industry leader uses debt conservatively, while the follower uses debt more aggressively and, as the result, defaults first. The model generates novel predictions about the leverage choices of the leader and the follower, their default likelihood, and the degree of leverage dispersion between competing firms. These predictions are strongly supported by the data. (JEL G13, G34, L13)
SLICC-Frailty Index is independently associated with impaired physical function, activities of daily living and quality of life measures
Authors: Keramiotou Kyriaki , Anagnostou Christos , Konstantonis George , Fragiadaki Kalliopi , Kataxaki Evangelia , Sfikakis Petros P , Tektonidou Maria G 
Published: January 2022

Abstract

Objective
The SLICC Frailty Index (SLICC-FI) was developed to assess health deficits including disease activity, organ damage, comorbidities and functional status. We examined any relationship between SLICC-FI and objective physical function measures, activities of daily living performance and quality of life in SLE.

Methods
SLICC-FI was estimated using data from patient files and patient-reported questionnaires. Jamar Dynamometer, pinch gauge and Purdue pegboard test measured grip strength, pinch strength and dexterity, respectively. Activities of daily living performance was assessed by the Disabilities of Arm, Shoulder and Hand (DASH) questionnaire and HAQ. Quality of life was evaluated by LupusQol questionnaire.

Results
This cross-sectional study included 240 SLE patients (90% female, mean (s.d.) age: 47.63 (13.01), median (IQR) disease duration: 9 (4–16)). Mean (s.d.) SLICC-FI was 0.09 (0.06). Forty-three (17.9%) patients were classified as robust, 105 (43.8%) as relatively less fit, 77 (32.1%) as least fit and 15 (6.2%) as frail. In univariate analysis, SLICC-FI was significantly associated with DASH and HAQ with an inverse association with grip strength, pinch strength and all purdue scores (all P &lt; 0.001). A negative correlation was found between SLICC-FI score and all LupusQoL domain scores (all P &lt; 0.001). All associations remained statistically significant in multivariate regression analysis, after adjustment for age, disease duration, SLEDAI-2K, SLICC, immunosuppressives, corticosteroids and Charlson score.

Conclusion
SLICC-FI is independently associated with poor physical function and activities of daily living performance and impaired quality of life and may help to identify patients in need of additional interventions beyond routine care.
Automatic analysis of muscular activity in the flexor digitorum superficialis muscles: a fast screening method for rapid eye movement sleep without atonia
Authors: Cesari Matteo , Heidbreder Anna , Gaig Carles , Bergmann Melanie , Brandauer Elisabeth , Iranzo Alex , Holzknecht Evi , Santamaria Joan , Högl Birgit , Stefani Ambra 
Published: January 2022

Abstract

Study objectives
To identify a fast and reliable method for rapid eye movement (REM) sleep without atonia (RWA) quantification.

Methods
We analyzed 36 video-polysomnographies (v-PSGs) of isolated REM sleep behavior disorder (iRBD) patients and 35 controls’ v-PSGs. Patients diagnosed with RBD had: i) RWA, quantified with a reference method, i.e. automatic and artifact-corrected 3-s Sleep Innsbruck Barcelona (SINBAR) index in REM sleep periods (RSPs, i.e. manually selected portions of REM sleep); and ii) v-PSG-documented RBD behaviors. We quantified RWA with other (semi)-automated methods requiring less human intervention than the reference one: the indices proposed by the SINBAR group (the 3-s and 30-s phasic flexor digitorum superficialis (FDS), phasic/”any”/tonic mentalis), and the REM atonia, short and long muscle activity indices (in mentalis/submentalis/FDS muscles). They were calculated in whole REM sleep (i.e. REM sleep scored following international guidelines), in RSPs, with and without manual artifact correction. Area under curves (AUC) discriminating iRBD from controls were computed. Using published cut-offs, the indices’ sensitivity and specificity for iRBD identification were calculated. Apnea-hypopnea index in REM sleep (AHIREM) was considered in the analyses.

Results
RWA indices from FDS muscles alone had the highest AUCs and all of them had 100% sensitivity. Without manual RSP selection and artifact correction, the “30-s phasic FDS” and the “FDS long muscle activity” had the highest specificity (85%) with AHIREM &lt; 15/h. RWA indices were less reliable when AHIREM≥15/h.

Conclusions
If AHIREM&lt;15/h, FDS muscular activity in whole REM sleep and without artifact correction is fast and reliable to rule out RWA.
Associations Between Physician Continuous Professional Development and Referral Patterns: A Systematic Review and Meta-Analysis
Authors: Cook David A. , Stephenson Christopher R. , Pankratz V. Shane , Wilkinson John M. , Maloney Stephen , Prokop Larry J. , Foo Jonathan 
Published: January 2022

Purpose
Both overuse and underuse of clinician referrals can compromise high-value health care. The authors sought to systematically identify and synthesize published research examining associations between physician continuous professional development (CPD) and referral patterns.

Method
The authors searched MEDLINE, Embase, PsycInfo, and the Cochrane Database on April 23, 2020, for comparative studies evaluating CPD for practicing physicians and reporting physician referral outcomes. Two reviewers, working independently, screened all articles for inclusion. Two reviewers reviewed all included articles to extract information, including data on participants, educational interventions, study design, and outcomes (referral rate, intended direction of change, appropriateness of referral). Quantitative results were pooled using meta-analysis.

Results
Of 3,338 articles screened, 31 were included. These studies enrolled at least 14,458 physicians and reported 381,165 referral events. Among studies comparing CPD with no intervention, 17 studies with intent to increase referrals had a pooled risk ratio of 1.91 (95% confidence interval: 1.50, 2.44; P < .001), and 7 studies with intent to decrease referrals had a pooled risk ratio of 0.68 (95% confidence interval: 0.55, 0.83; P < .001). Five studies did not indicate the intended direction of change. Subgroup analyses revealed similarly favorable effects for specific instructional approaches (including lectures, small groups, Internet-based instruction, and audit/feedback) and for activities of varying duration. Four studies reported head-to-head comparisons of alternate CPD approaches, revealing no clear superiority for any approach. Seven studies adjudicated the appropriateness of referral, and 9 studies counted referrals that were actually completed (versus merely requested).

Conclusions
Although between-study differences are large, CPD is associated with statistically significant changes in patient referral rates in the intended direction of impact. There are few head-to-head comparisons of alternate CPD interventions using referrals as outcomes.
10-year prevalence of diagnostic and screening colonoscopy use in Germany: a claims data analysis
Authors: Hornschuch Michel , Schwarz Sarina , Haug Ulrike 
Published: January 2022

Introduction
Studies providing detailed information on colonoscopy use are important for the interpretation of patterns and trends in colorectal cancer incidence and mortality, but there is a lack of such studies from Germany. To fill this gap, we aimed to describe the 10-year prevalence of colonoscopy use based on German health claims data.

Methods
Using the German Pharmacoepidemiological Research Database (short GePaRD; claims data from ~20% of the German population), we determined the 10-year prevalence of colonoscopy use for the year 2017. We determined this prevalence for any colonoscopy, screening (reimbursable from age 55) and diagnostic colonoscopy, stratified by sex, age, educational level and regional factors (e.g. federal state, physicians density in the district of residence).

Results
In men, the 10-year prevalence of colonoscopy use was as follows (not all age groups reported): 30–34 years: 8%, 40–44 years: 12%, 50–54 years: 21%, 55–59 years: 33% (screening: 10%), 60–64 years: 44% (screening: 23%), 70–74 years: 53% (screening: 23%), 80–84 years: 52% (screening: 15%). In women, the prevalences were similar, with differences mostly less than or equal to 3 percentage points. Also, in analyses stratified by educational level or regional factors, prevalences were mostly similar or varied by less than or equal to 4 percentage points.

Conclusion
In 2017, about 45–50% of men and women in Germany aged 60–84 years had any colonoscopy in the previous 10 years, and about 11–26% had a screening colonoscopy. Our findings suggest no relevant social or regional disparities in the utilization of colonoscopy in Germany.
Chronic fine particulate matter exposure, habitual exercise, and dyslipidemia: A longitudinal cohort study
Authors: Zeng Yi Qian , Chang Ly-yun , Guo Cui , Lin Changqing , Bo Yacong , Wong Martin C. S. , Tam Tony , Lau Alexis K. H. , Lao Xiang Qian 
Published: January 2022

Background:
Physical activity may increase the intake of air pollutants due to a higher ventilation rate, which may exacerbate the adverse health effects. This study investigated the combined effects of habitual exercise and long-term exposure to fine particulate matter (PM2.5) on the incidence of dyslipidemia in a large longitudinal cohort in Taiwan.

Methods:
A total of 121,948 adults (≥18 years) who received at least two medical examinations from 2001 to 2016 were recruited, yielding 407,821 medical examination records. A satellite-based spatiotemporal model was used to estimate the 2-year average PM2.5 concentration (i.e., the year of and the year before the medical examination) at each participant’s address. Information on habitual exercise within 1 month before the medical examination was collected using a standard self-administered questionnaire. A Cox regression model with time-dependent covariates was used to investigate the combined effects.

Results:
Compared with inactivity, moderate and high levels of exercise were associated with a lower incidence of dyslipidemia, with hazard ratios (HRs) (95% confidence intervals [CIs]) of 0.91 (0.88, 0.94) and 0.73 (0.71, 0.75), respectively. Participants with a moderate (22.37–25.96 μg/m3) or high (>25.96 μg/m3) level of PM2.5 exposure had a higher incidence of dyslipidemia than those with a low level of PM2.5 exposure (≤22.37 μg/m3), with HRs (95% CIs) of 1.36 (1.32, 1.40), and 1.90 (1.81, 1.99), respectively. We observed a statistically significant, but minor, interaction effect of PM2.5 exposure and exercise on the development of dyslipidemia, with an overall hazard ratios (95% CI) of 1.08 (1.05, 1.10), indicating that an incremental increase in the level of exercise was associated with an 8% increase in the risk of dyslipidemia associated with every 10 μg/m3 increase in PM2.5 exposure. However, the negative association between habitual exercise and dyslipidemia remained, regardless of the level of PM2.5 exposure, suggesting that the benefits of increased habitual exercise outweighed the adverse effects of the increase in PM2.5 intake during exercise.

Conclusions:
Increased levels of exercise and reduced levels of PM2.5 exposures were associated with a lower incidence of dyslipidemia. Although an increase in habitual exercise slightly increased the risk of dyslipidemia associated with PM2.5 exposure, the benefits of the increased habitual exercise outweighed the risks. Our findings suggest that habitual exercise is an effective approach for dyslipidemia prevention, even for people residing in relatively polluted areas.