bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effectiveness of tacrolimus concomitant with biological disease-modifying antirheumatic drugs in patients with rheumatoid arthritis
Authors: Terabe Kenya , Takahashi Nobunori , Asai Shuji , Hirano Yuji , Kanayama Yasuhide , Yabe Yuichiro , Oguchi Takeshi , Fujibayashi Takayoshi , Ishikawa Hisato , Hanabayashi Masahiro , Hattori Yosuke , Suzuki Mochihito , Kishimoto Kenji , Ohashi Yoshifumi , Imaizumi Takahiro , Imagama Shiro , Kojima Toshihisa 
Published: March 2022

ABSTRACTObjectivesThe study aimed to investigate the effectiveness and tolerance of biological disease-modifying antirheumatic drugs (bDMARDs) therapy administered concomitantly with tacrolimus (TAC) treatment in patients with rheumatoid arthritis.Methods2792 patients who underwent therapy with five bDMARDs (etanercept: ETN, adalimumab, golimumab, tocilizumab, and abatacept: ABT) were enrolled. Among the study subjects, 1582 were concomitant methotrexate (MTX group), 147 were concomitant TAC (TAC group), and 1063 were non-concomitant MTX and TAC (non-MTX/TAC group). The primary outcome was the incident rate of discontinuation of bDMARDs by adverse events (AEs) or loss of efficacy.ResultsConcerning the analysis for each reasons of discontinuation, including AEs and loss of efficacy, the hazards ratio (HR) was significantly lower in the TAC group than in non-MTX/TAC groups (AEs: HR = 0.39, 95% confidence interval, 0.23–0.68, loss of efficacy: HR = 0.49, 95% confidence interval, 0.30–0.78). The loss of efficacy with the use of ETN and ABT was lower in the TAC group than in non-MTX/TAC groups. Concomitant TAC did not induce elevated risk for discontinuation of AEs in all bDMARD analyses.ConclusionsConcomitant TAC with ABT or ETN showed higher retention rates than bDMARDs therapy without TAC or MTX. AEs did not increase over long-term observation.
scREMOTE: Using multimodal single cell data to predict regulatory gene relationships and to build a computational cell reprogramming model
Authors: Tran Andy , Yang Pengyi , Yang Jean Y H , Ormerod John T 
Published: March 2022

Abstract
Cell reprogramming offers a potential treatment to many diseases, by regenerating specialized somatic cells. Despite decades of research, discovering the transcription factors that promote cell reprogramming has largely been accomplished through trial and error, a time-consuming and costly method. A computational model for cell reprogramming, however, could guide the hypothesis formulation and experimental validation, to efficiently utilize time and resources. Current methods often cannot account for the heterogeneity observed in cell reprogramming, or they only make short-term predictions, without modelling the entire reprogramming process. Here, we present scREMOTE, a novel computational model for cell reprogramming that leverages single cell multiomics data, enabling a more holistic view of the regulatory mechanisms at cellular resolution. This is achieved by first identifying the regulatory potential of each transcription factor and gene to uncover regulatory relationships, then a regression model is built to estimate the effect of transcription factor perturbations. We show that scREMOTE successfully predicts the long-term effect of overexpressing two key transcription factors in hair follicle development by capturing higher-order gene regulations. Together, this demonstrates that integrating the multimodal processes governing gene regulation creates a more accurate model for cell reprogramming with significant potential to accelerate research in regenerative medicine.
Neurocognitive function and survival in children with average-risk medulloblastoma treated with hyperfractionated radiation therapy alone: Long-term mature outcomes of a prospective study
Authors: Gupta Tejpal , Kalra Babusha , Goswami Savita , Deodhar Jayita , Rane Pallavi , Epari Sridhar , Moiyadi Aliasgar , Dasgupta Archya , Chatterjee Abhishek , Chinnaswamy Girish 
Published: March 2022

Abstract

Background
The purpose of this study was to report long-term neurocognitive and clinical outcomes in children treated for average-risk medulloblastoma with hyperfractionated radiation therapy (HFRT) alone.

Methods
Between 2006 and 2010, 20 children with rigorously staged average-risk medulloblastoma were treated on a prospective study with HFRT without upfront adjuvant systemic chemotherapy after written informed consent. HFRT was delivered as twice-daily fractions (1 Gy/fraction, 6–8 hours apart, 5 days/week) to craniospinal axis (36 Gy/36 fractions) plus conformal tumor-bed boost (32 Gy/32 fractions). Neurocognitive function was assessed at baseline and periodically on follow-up using age-appropriate intelligence quotient (IQ) scales.

Results
Median age was 8 years (range 5–14 years) with 70% being males. Mean and standard deviation (SD) scores at baseline were 90.5 (SD = 17.08), 88 (SD = 16.82) and 88 (SD = 17.24) for Verbal Quotient (VQ), Performance Quotient (PQ), and Full-Scale IQ (FSIQ) respectively. Mean scores remained stable in the short-to-medium term but declined gradually beyond 5 years with borderline statistical significance for VQ (P = .042), but nonsignificant decline in PQ (P = .259) and FSIQ (P = .108). Average rate of neurocognitive decline was &lt;1 IQ point per year over a 10-year period. Regression analysis stratified by age, gender, and baseline FSIQ failed to demonstrate any significant impact of the tested covariates on longitudinal neurocognitive function. At a median follow-up of 145 months, 10-year Kaplan-Meier estimates of progression-free survival and overall survival were 63.2% and 74.1% respectively.

Conclusion
HFRT alone without upfront adjuvant chemotherapy in children with average-risk medulloblastoma is associated with modest decline in neurocognitive functioning with acceptable long-term survival outcomes and may be most appropriate for resource-constrained settings.
Corticosteroids use and neurocognitive functioning in patients with recurrent glioblastoma: Evidence from European Organization for Research and Treatment of Cancer (EORTC) trial 26101
Authors: Caramanna Ivan , de Kort Julie M , Brandes Alba A , Taal Walter , Platten Michael , Idbaih Ahmed , Frenel Jean Sebastien , Wick Wolfgang , Preetha Chandrakanth Jayachandran , Bendszus Martin , Vollmuth Philipp , Reijneveld Jaap C , Klein Martin 
Published: March 2022

AbstractBackgroundIn patients with recurrent glioblastoma, corticosteroids are frequently used to mitigate intracranial pressure and to improve patient neurological functioning. To date, in these patients, no systematic studies have been performed to assess neurocognitive functioning (NCF) in relation to corticosteroid treatment.MethodsUsing baseline data (ie, prior to randomization) of European Organization for Research and Treatment of Cancer (EORTC) trial 26101, we performed regression analysis to assess the predictive value of corticosteroid intake on performance of the EORTC brain tumor clinical trial NCF test battery. The battery is comprised of the Hopkins Verbal Learning Test—Revised (HVLT-R), Controlled Oral Word Association Test (COWA), and Trail Making Test (A and B).ResultsOut of 321 patients, 148 (46.1%) were not using corticosteroids, and 173 were using dexamethasone (34.3%), methylprednisolone (9.7%), or other corticosteroids (9.9%). Patients on corticosteroids had worse performance on all neurocognitive tests. Regression analyses demonstrated a negative association between corticosteroids use and the HVLT-R free recall score (R2 change = 0.034, F change (1, 272) = 13.392, P &lt; .001) and HVLT-R Delayed Recall score (R2 change = 0.028, F change (1, 270) = 10.623, P = .002). No statistically significant association was found for HVLT-R Delayed recognition, COWA, TMT part A and TMT part B (P &gt; .05).ConclusionsGlioblastoma patients prescribed with corticosteroids show poorer memory functions, expressive language, visual-motor scanning speed, and executive functioning than patients not using corticosteroids. Furthermore, we found a negative association between corticosteroid intake and memory functions. The possibility of deleterious effects of corticosteroids on NCF should be considered during clinical decision making.
Platinum-Group Element Geochemistry and Magma Evolution of the Mount Hagen (Papua New Guinea) Magmatic System
Authors: Misztela M A , Campbell I H , Arculus R J 
Published: March 2022

Abstract
Mount Hagen is a mid-Pleistocene stratovolcano located in the Papua New Guinea Highlands. It was selected for this study because of (1) its close location to several giant Cu–Au porphyry deposits in the region; (2) its high-K calc-alkaline character (absarokite–shoshonite) and (3) its wide compositional range (2 to 12 wt % MgO). Whole-rock geochemistry, petrography and QEMSCAN observations are consistent with fractional crystallisation of the evolving magma being controlled by the phases now represented by the megacrysts in the lavas: olivine and clinopyroxene at high MgO and hornblende and plagioclase at low MgO. However, the role of plagioclase is enigmatic. Although it is an abundant megacryst phase in the low-MgO samples, plagioclase has little or no influence on fractional crystallisation, suggesting that it may be an antecryst. The appearance of plagioclase megacrysts does not slow the rate of increase in Al2O3 or Sr with decreasing sample MgO and the low-MgO samples do not have Eu anomalies. At ~5.5 wt % MgO, there are significant changes in the system that are inconsistent with simple fractional crystallisation. These changes include hornblende and plagioclase replacing olivine and clinopyroxene as the principal megacryst phases, a sharp rise in platinum-group elements (PGE) concentrations, the brief reappearance of high Fo olivine megacrysts and reversed zoning in the plagioclase megacrysts. These changes are interpreted to have resulted from a new pulse of magma entering the system, with higher water, MgO, SiO2 and PGE concentrations than the original parent magma. Scatter in the PGE data is attributed to the presence of micronuggets in all samples, including the most mafic samples. We conclude that the magma system became sulphide saturated during an early stage in its fractionation history, probably before leaving the crust to deep crustal magma chamber, and then became undersaturated as a consequence of decreasing pressure as magma ascended into a mid-crustal magma chamber. The early saturation episode had a pronounced influence on PGE concentration but had little affect Cu and Au, due to their lower partition coefficient into sulphides. The magma became sulphide saturated again in the crustal magma chamber at ~8.5 wt % MgO, this time affecting all chalcophile elements. Given the early episodes of sulphide saturation, depletion in Au in the Mount Hagen magma system and the absence of a known porphyry system, it is unlikely that Mount Hagen produced economic porphyry mineralisation.
The Disparate Effect of Nudges on Minority Groups
Authors: Haran Rosen Maya , Sade Orly 
Published: March 2022

AbstractWe compare the effect of a text message sent to mobile phones on the actions of minority groups versus the general population in Israel. Using proprietary data from a dedicated survey, we show that the text message had an overall positive effect, but a significantly smaller effect on minority groups. We provide insights into potential channels (low digital literacy, low financial literacy, and low trust) that contribute to the differential effect. This evidence suggests that policy interventions relying on voluntary take-up by participants may be disproportionately taken up by nonmarginalized groups, an unintended effect that can exacerbate rather than mitigate disparities. (JEL D14, G38, G41, G51, G53, I38)
Sleep–wake states change the interictal localization of candidate epileptic source generators
Authors: McLeod Graham A , Abbasian Parandoush , Toutant Darion , Ghassemi Amirhossein , Duke Tyler , Rycyk Conrad , Serletis Demitre , Moussavi Zahra , Ng Marcus C 
Published: March 2022

Abstract

Study Objectives
To compare estimated epileptic source localizations from 5 sleep–wake states (SWS): wakefulness (W), rapid eye movement sleep (REM), and non-REM 1-3.

Methods
Electrical source localization (sLORETA) of interictal spikes from different SWS on surface EEG from the epilepsy monitoring unit at spike peak and take-off, with results mapped to individual brain models for 75% of patients. Concordance was defined as source localization voxels shared between 2 and 5 SWS, and discordance as those unique to 1 SWS against 1–4 other SWS.

Results
563 spikes from 16 prospectively recruited focal epilepsy patients across 161 day-nights. SWS exerted significant differences at spike peak but not take-off. Source localization size did not vary between SWS. REM localizations were smaller in multifocal than unifocal patients (28.8% vs. 54.4%, p = .0091). All five SWS contributed about 45% of their localizations to converge onto 17.0 ± 15.5% voxels. Against any one other SWS, REM was least concordant (54.4% vs. 66.9%, p = .0006) and most discordant (39.3% vs. 29.6%, p = .0008). REM also yielded the most unique localizations (20.0% vs. 8.6%, p = .0059).

Conclusions
REM was best suited to identify candidate epileptic sources. sLORETA proposes a model in which an “omni-concordant core” of source localizations shared by all five SWS is surrounded by a “penumbra” of source localizations shared by some but not all SWS. Uniquely, REM spares this core to “move” source voxels from the penumbra to unique cortex not localized by other SWS. This may reflect differential intra-spike propagation in REM, which may account for its reported superior localizing abilities.
Re-examining extreme sleep duration in bats: implications for sleep phylogeny, ecology, and function
Authors: Harding Christian D , Yovel Yossi , Peirson Stuart N , Hackett Talya D , Vyazovskiy Vladyslav V 
Published: March 2022

AbstractBats, quoted as sleeping for up to 20 h a day, are an often used example of extreme sleep duration amongst mammals. Given that duration has historically been one of the primary metrics featured in comparative studies of sleep, it is important that species specific sleep durations are well founded. Here, we re-examined the evidence for the characterization of bats as extreme sleepers and discuss whether it provides a useful representation of the sleep behavior of Chiroptera. Although there are a wealth of activity data to suggest that the diurnal cycle of bats is dominated by rest, estimates of sleep time generated from electrophysiological analyses suggest considerable interspecific variation, ranging from 83% to a more moderate 61% of the 24 h day spent asleep. Temperature-dependent changes in the duration and electroencephalographic profile of sleep suggest that bats represent a unique model for investigating the relationship between sleep and torpor. Further sources of intra-specific variation in sleep duration, including the impact of artificial laboratory environments and sleep intensity, remain unexplored. Future studies conducted in naturalistic environments, using larger sample sizes and relying on a pre-determined set of defining criteria will undoubtedly provide novel insights into sleep in bats and other species.
From dawn to dusk—mimicking natural daylight exposure improves circadian rhythm entrainment in patients with severe brain injury
Authors: Angerer Monika , Pichler Gerald , Angerer Birgit , Scarpatetti Monika , Schabus Manuel , Blume Christine 
Published: March 2022

AbstractStudy ObjectivesWhile light therapy has proven effective in re-entraining circadian rhythms, the potential of such an intervention has not been evaluated systematically in post-comatose patients with disorders of consciousness (DOC), who often have strongly altered circadian rhythms.MethodsWe recorded skin temperature over 7–8 days in patients with DOC in each of two conditions: habitual light (HL), and dynamic daylight (DDL) condition. While patients were in a room with usual clinic lighting in the HL condition, they were in an otherwise comparable room with biodynamic lighting (i.e. higher illuminance and dynamic changes in spectral characteristics during the day) in the DDL condition. To detect rhythmicity in the patients’ temperature data, we computed Lomb–Scargle periodograms and analyzed normalized power, and peak period. Furthermore, we computed interdaily stability and intradaily variability, which provide information about rhythm entrainment and fragmentation.ResultsWe analyzed data from 17 patients with DOC (i.e. unresponsive wakefulness syndrome [n = 15] and minimally conscious state [n = 2]). The period length of the patients’ temperature rhythms was closer to 24 h in the DDL as compared to the HL condition (median median deviation from 24 h: DDL = 0.52 h, HL = 3.62 h). Specifically, in 11/17 (65%) patients the period length was closer to 24 h in the DDL condition. Furthermore, the patients’ rhythm was more pronounced, more stable, and less variable in the DDL condition.ConclusionsOur results indicate that DDL stimulation entrains and stabilizes circadian rhythms. This highlights the importance of adequate room lighting as an adjunct therapeutic approach for improving circadian rhythms in severely brain-injured patients.Trial Registration InformationGerman Clinical Trials Register (DRKS00016041); registration: 18.01.2019; recording start: 04.06.2019 https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00016041
Race, Gender, and Police Violence in the Shadow of Controlling Images
Authors: Remster Brianna , Smith Chris M , Kramer Rory 
Published: March 2022

Abstract
Despite the emergence of the #SayHerName movement alongside #BlackLivesMatter, research on police encounters is rarely intersectional and has largely neglected the potentially violent consequences of gendered and racialized “controlling images.” Using New York City investigatory stop data (2007–2014), and drawing on controlling images theory, our analysis shows that Black men and women experience higher rates of police violence than White men and women. Within race, analyses indicate that Black men experience more police violence than Black women. The same gender gap exists for Whites, Asians, and Latinx persons, suggesting that broad cultural perceptions of femininity and masculinity shape police violence. However, these gendered frames mostly dissolve in instances of potentially fatal violence, as we find no gender differences within race or ethnicity in these extreme cases with one exception: police point their guns at Black men slightly more than at Black women. Further, the controlling image criminalizing Black men casts a long shadow—police are more likely to use violence on individuals stopped in the company of a Black man across gender, race, and ethnicity. This study provides a comprehensive, intersectional analysis of police encounters, both reaffirming and extending controlling images to understand why race, ethnicity, and gender disparities in state violence experiences persist.
Applying the Value Transformation Framework in Federally Qualified Health Centers to Increase Clinical Measures Performance
Authors: Modica Cheryl , Bay Curt , Lewis Joy H. , Silva Camila 
Published: March 2022

ABSTRACT

Introduction:
The transition in health care from a volume-based to value-based model of care, combined with pressures brought about by the COVID-19 pandemic, makes the need for efficiency and coordination of the health center system imperative. The Value Transformation Framework (VTF), developed with health centers in mind, provides an organizing framework to support transformation of infrastructure, care delivery, and people systems.

Methods:
NACHC applied the VTF within a cohort of health centers across the country to drive systems change and improve performance on measures of clinical care.

Results:
A comparison of health centers “participating” in application of the VTF relative to “nonparticipating” health centers nationally showed improvement during 3 years of program implementation. Significant differences (p < .05) favoring health centers who participated were noted for screening of colorectal cancer (p < .001), depression (p < .001), hypertension (p < .001), obesity (p = .001), and cervical cancer (p = .011). Performance for diabetes control also favored participating programs, although the difference did not quite reach significance (p = .45).

Conclusions:
Applying a systems approach, organized by the VTF, with evidence-based interventions and deployed in a learning community, can result in improved performance across multiple measures of clinical care.
Higher polygenic risk for melanoma is associated with improved survival
Authors: Seviiri Mathias , Scolyer Richard A. , Bishop D. Timothy , Iles Mark M. , Lo Serigne N. , Stretch Johnathan R. , Saw Robyn P.M. , Nieweg Omgo E. , Shannon Kerwin F. , Spillane Andrew J. , Gordon Scott D. , Olsen Catherine M. , Whiteman David C. , Landi Maria T. , Thompson John F. , Long Georgina V. , MacGregor Stuart , Law Matthew H. 
Published: March 2022

ABSTRACTBackgroundAlthough there are well-known prognostic factors for survival from cutaneous melanoma (CM) such as primary tumour thickness and stage of the tumour at diagnosis, the role of germline genetic factors in determining survival is not well understood.ObjectiveTo perform a genome-wide association study (GWAS) meta-analysis of melanoma-specific survival (MSS), and test whether a CM-susceptibility polygenic risk score (PRS) is associated with MSS.MethodsWe conducted two Cox proportional-hazard GWAS of MSS using data from the Melanoma Institute Australia (MIA; 5,762 patients with melanoma; 800 deaths from melanoma) and UK Biobank (UKB: 5,220 patients with melanoma; 241 deaths from melanoma). The GWAS were adjusted for age, sex and the first ten genetic principal components, and combined in a fixed-effects inverse-variance-weighted meta-analysis. Significant (P<5×10−8) results were investigated in the Leeds Melanoma Cohort (LMC; 1,947 patients with melanoma; 370 melanoma deaths). We also developed a CM-susceptibility PRS using a large independent GWAS meta-analysis (23,913 cases, 342,870 controls). The PRS was tested for an association with MSS in the MIA and UKB cohorts, with replication in the LMC.ResultsTwo loci were significantly associated with MSS in the meta-analysis of MIA and UKB with lead SNPs rs41309643 (G allele frequency 1.6%, hazard ratio [HR] 2.09, 95% confidence interval [CI] 1.61-2.71, P=2.08×10−8) on chromosome 1, and rs75682113 (C allele frequency 1.8%, HR=2.38, 95% CI=1.77—3.21, P=1.07×10−8) on chromosome 7. While neither SNP replicated (P>0.05) in the LMC, rs75682113 was significantly associated in the combined discovery and replication sets and requires confirmation in additional cohorts.After adjusting for age at diagnosis, sex and the first ten principal components, a one standard deviation increase in the CM-susceptibility PRS was associated with improved MSS in the discovery meta-analysis (HR=0.88, 95% CI=0.83—0.94, P=6.93×10−5; I2=88%). The association with the PRS was not replicated (P > 0.05) in LMC, but remained significantly associated with MSS in the meta-analysis of the discovery and replication results.ConclusionWe found two loci potentially associated with MSS, and evidence that increased germline genetic susceptibility to develop CM may be associated with improved MSS.