bluuebunny/crossref_metadata_2025_split huggingface dataset:
INSPECT: A Retrospective Study to Evaluate Long-term Effectiveness and Safety of Darvadstrocel in Patients With Perianal Fistulizing Crohn’s Disease Treated in the ADMIRE-CD Trial
Authors: Panés Julian , Bouma Gerd , Ferrante Marc , Kucharzik Torsten , Nachury Maria , de la Portilla de Juan Fernando , Reinisch Walter , Selvaggi Francesco , Tschmelitsch Jörg , Brett Neil R , Ladouceur Martin , Binek Matthias , Hantsbarger Gary , Campbell-Hill Sarah , Karki Chitra , Buskens Christianne 
Published: January 2022

Abstract

Background
The efficacy of a single administration of darvadstrocel (expanded allogeneic adipose-derived mesenchymal stem cells) for treating complex perianal fistulas in patients with Crohn’s disease was demonstrated in a randomized, double-blind trial (ADMIRE-CD [Adipose Derived Mesenchymal Stem Cells for Induction of Remission in Perianal Fistulizing Crohn\'s Disease] trial). The current chart review study (INSPECT [A retrospectIve chart review study evaluatINg the longer-term effectiveneSs of darvadstrocel in PatiEnts who CompleTed ADMIRE-CD]) evaluated the longer-term effectiveness and safety of darvadstrocel.

Methods
Eligible patients had completed at least 52 weeks in the ADMIRE-CD trial. Data on clinical remission and fistula relapse outcomes were collected retrospectively at 104 and 156 weeks after treatment. Adverse events of special interest (tumorigenicity and ectopic tissue formation) were collected up to 208 weeks after treatment.

Results
Eighty-nine patients were included (43 darvadstrocel patients, 46 control subjects). At 52, 104, and 156 weeks posttreatment, clinical remission was observed in 29 (67.4%) of 43, 23 (53.5%) of 43, and 23 (53.5%) of 43 darvadstrocel-treated patients, compared with 24 (52.2%) of 46, 20 (43.5%) of 46, and 21 (45.7%) of 46 control subjects, respectively. In patients with clinical remission at week 52, this remission was sustained at 104 and 156 weeks after treatment in 19 (65.5%) of 29 and 16 (55.2%) of 29 darvadstrocel-treated patients and in 17 (70.8%) of 24 and 13 (54.2%) of 24 control subjects, respectively. Time to fistula relapse and incidence of fistula relapse or new fistula occurrence were not significantly different between groups. Tumorigenicity was reported for 1 (2.2%) patient in the control group (malignant epidermoid carcinoma). No ectopic tissue formation was reported.

Conclusions
Real-world follow-up of patients from the ADMIRE-CD trial indicates that clinical remission of complex perianal fistulas can be sustained in the long term irrespective of whether it is achieved through darvadstrocel administration or maintenance treatment regimens and confirms a favorable long-term safety profile of darvadstrocel.
The avoidance of unwanted catch and cooperation: the case of the British Columbia groundfish trawl fishery
Authors: Grønbæk L , Lindroos M , Munro G , Pintassilgo P , Turris B 
Published: January 2022

AbstractThis paper focuses on a particularly successful avoidance of unwanted catch of protected, endangered, and threatened (PET) species in the form of ecologically important sponge and coral, to be found off Canada's Pacific coast. The fishery causing the unwanted catch—the British Columbia groundfish trawl fishery. A campaign to protect the sponge/coral led by environmental NGOs (ENGOs) resulted in the industry's access to the key California market being threatened. For reasons explained, the national resource manager's ability to take effective direct action had become severely compromised. The groundfish trawl fishing industry responded to the economic threat with a bottom up approach to the unwanted catch problem, by negotiating a habitat agreement with a consortium of ENGOs, with the blessing and full support of the national resource manager. The agreement, now in its tenth year of operation, has proved to be a remarkable success in avoidance of unwanted catch. The paper argues that the success rests fundamentally upon the fact that the fishers have been and are playing a stand alone stable cooperative game, which has led them in turn to play stable cooperative games with both the national resource manager and the ENGO consortium. The paper analyses the factors leading to the stand alone stable cooperative fisher game, doing so by necessity through the lens of game theory.
Heartmate 3 implantation in small patients: CT-guided chest diameter assessment
Authors: Van Puyvelde Joeri , Jacobs Steven , Vlasselaers Dirk , Meyns Bart 
Published: January 2022

Abstract
In recent years, the Heartmate 3 (HM3) has largely replaced the use of other intracorporeal left ventricular assist devices in the adult field. Because the HM3 is larger than the Heartware Ventricular Assist Device, the general consensus was that for small patients, the Heartware Ventricular Assist Device was the most appropriate implantable device option. Our goal was to describe our experiences with the successful implantation of the HM3 in 2 children, aged 9 and 11. We report on the chest cavity dimensions, as measured on computed tomography, that can be used to assess the feasibility of HM3 implantation in small patients.
Immunogenicity of a Third Scheduled Dose of Rotarix in Australian Indigenous Infants: A Phase IV, Double-blind, Randomized, Placebo-Controlled Clinical Trial
Authors: Middleton Bianca F , Danchin Margie , Jones Mark A , Leach Amanda J , Cunliffe Nigel , Kirkwood Carl D , Carapetis Jonathan , Gallagher Sarah , Kirkham Lea-Ann , Granland Caitlyn , McNeal Monica , Marsh Julie A , Waddington Claire S , Snelling Thomas L 
Published: January 2022

Abstract

Background
Rotarix (GlaxoSmithKline) oral rotavirus vaccine is licensed as 2 doses in the first 6 months of life. In settings with high child mortality rates, clinical protection conferred by 2 doses of Rotarix is reduced. We assessed vaccine immune response when an additional dose of Rotarix was given to Australian Aboriginal children 6 to &lt;12 months old.

Methods
ORVAC is a 2-stage, double-blind, randomized, placebo-controlled trial. Australian Aboriginal children 6 to &lt;12 months old who had received 1 or 2 prior doses of Rotarix rotavirus vaccine were randomized 1:1 to receive an additional dose of Rotarix or matched placebo. The primary immunological end point was seroresponse defined as an anti-rotavirus immunoglobulin A level ≥20 AU/mL, 28–56 days after the additional dose of Rotarix or placebo.

Results
Between March 2018 and August 2020, a total of 253 infants were enrolled. Of these, 178 infants (70%) had analyzable serological results after follow-up; 89 were randomized to receive Rotarix, and 89 to receive placebo. The proportion with seroresponse was 85% after Rotarix compared with 72% after placebo. There were no occurrences of intussusception or any serious adverse events.

Conclusions
An additional dose of Rotarix administered to Australian Aboriginal infants 6 to &lt;12 months old increased the proportion with a vaccine seroresponse.

Clinical Trials Registration
NCT02941107.
Strategic Litigation in International Criminal Justice
Authors: Jeßberger Florian , Steinl Leonie 
Published: January 2022

Abstract
This article inquires into strategic litigation in international criminal justice. Drawing on the findings of an empirical study, it sheds light on the practice and self-perception of Strategic Litigation NGOs (so-called SLiNGOs) who employ international criminal law not only as an advocacy tool but use litigation to target perpetrators of international crimes as part of a larger juridical–political strategy transcending the individual case. Following a brief reflection on the role and significance of NGOs in international criminal justice in general and an examination of the basic idea of strategic litigation, the article delves into an analysis of the concept of strategic litigation as employed by SLiNGOs as well as the various functions of strategic litigation specifically in the international criminal justice context. Relying on interviews with SLiNGO representatives, the authors examine whether SLiNGOs — in their self-perception — serve merely as ‘assistant prosecutors’ or rather as kickstarters, pacemakers and watchdogs of the enforcement of international criminal law. They further explore the counter-hegemonic potential of strategic litigation and SLiNGO’s attitudes towards international criminal justice as such. Analysing potential pitfalls and critiques directed at strategic litigation and the responses of SLiNGOs to such criticisms, the authors conclude that strategic litigation can indeed fill a gap in the current state-based system of international criminal justice and suggest an agenda for further research.
A New Approach to Disease, Risk, and Boundaries Based on Emergent Probability
Authors: Daly Patrick 
Published: January 2022

AbstractThe status of risk factors and disease remains a disputed question in the theory and practice of medicine and healthcare, and so does the related question of delineating disease boundaries. I present a framework based on Bernard Lonergan’s account of emergent probability for differentiating (1) generically distinct levels of systematic function within organisms and between organisms and their environments and (2) the methods of functional, genetic, and statistical investigation. I then argue on this basis that it is possible to understand disease in terms of biological or higher intra-level dysfunction, risk factors—including genetic risk factors—in terms of statistical inter-level conditioning of a given stage or developmental sequence of systematic functioning, and the empirical boundaries of disease in terms of the limits of both functional categorization (from an epistemic standpoint) and upper-level integration of lower-level processes and events (from an ontological standpoint).
Inflammation, Attention, and Processing Speed in Patients With Breast Cancer Before and After Chemotherapy
Authors: Belcher Elizabeth K , Culakova Eva , Gilmore Nikesha J , Hardy Sara J , Kleckner Amber S , Kleckner Ian R , Lei Lianlian , Heckler Charles , Sohn Michael B , Thompson Bryan D , Lotta Louis T , Werner Zachary A , Geer Jodi , Hopkins Judith O , Corso Steven W , Rich David Q , van Wijngaarden Edwin , Janelsins Michelle C 
Published: January 2022

AbstractBackgroundInflammation may contribute to cognitive difficulties in patients with breast cancer. We tested 2 hypotheses: inflammation is elevated in patients with breast cancer vs noncancer control participants and inflammation in patients is associated with worse attention and processing speed over the course of chemotherapy.MethodsSerum cytokines (interleukin [IL]–4, 6, 8, 10; tumor necrosis factor [TNF]–α) and soluble receptors [sTNFRI, II]) were measured in 519 females with breast cancer before and after chemotherapy and 338 females without cancer serving as control participants. Attention and processing speed were measured by Rapid Visual Processing (RVP), Backward Counting (BCT), and Trail Making-A (TMT-A) tests. Linear regression models examined patient vs control cytokines and receptor levels, adjusting for covariates. Linear regression models also examined relationships between patient cytokines and receptor levels and test performance, adjusting for age, body mass index, anxiety, depression, cognitive reserve, and chemotherapy duration. Statistical tests were 2-sided (α = .05).ResultssTNFRI and sTNFRII increased over time in patients relative to controls, whereas IL-4, IL-6, and IL-10 decreased. Prechemotherapy, higher IL-8 associated with worse BCT (β = 0.610, SE = 0.241, P = .01); higher IL-4 (β = −1.098, SE = 0.516, P = .03) and IL-10 (β = −0.835, SE = 0.414, P = .04) associated with better TMT-A. Postchemotherapy, higher IL-8 (β = 0.841, SE = 0.260, P = .001), sTNFRI (β = 6.638, SE = 2.208, P = .003), and sTNFRII (β = 0.913, SE = 0.455, P = .045) associated with worse BCT; higher sTNFRII also associated with worse RVP (β = −1.316, SE = 0.587, P = .03). At prechemotherapy, higher IL-4 predicted RVP improvement over time (β = 0.820, SE = 0.336, P = .02); higher sTNFRI predicted worse BCT over time (β = 5.566, SE = 2.367, P = .02). Longitudinally, increases in IL-4 associated with BCT improvement (β = −0.564, SE = 0.253, P = .03).ConclusionsGenerally, worse attention and processing speed were associated with higher inflammatory cytokines and receptors and lower anti-inflammatory cytokines in patients; future confirmatory studies are needed.
Counting Advanced Precancerous Lesions as True Positives When Determining Colorectal Cancer Screening Test Specificity
Authors: Ladabaum Uri , Church Timothy R , Feng Ziding , Ransohoff David F , Schoen Robert E 
Published: January 2022

Abstract
The landmark Centers for Medicare & Medicaid Services (CMS) decision memo on blood-based biomarkers to screen for colorectal cancer (CRC) sets thresholds of 74% or higher for sensitivity and 90% or higher for specificity for CRC. This approach does not consider detection of advanced precancerous lesions as true positives. We contrasted the impact of counting advanced precancerous lesions as true vs false positives and projected CRC outcomes under contrasting tests in a validated model. A test with the threshold performance set by CMS decreased CRC incidence by 30% and CRC mortality by 48% in individuals aged 45 years. If this test also detected advanced precancerous lesions with 30% sensitivity, CRC incidence decreased by 45% and mortality by 58%, but the CRC specificity of the test of only 88% would not satisfy the CMS threshold. CMS should reconsider its definition of threshold specificity for CRC screening biomarkers. Future coverage determinations on biomarkers to screen for cancer should consider detection of relevant precursor lesions and projected outcomes.
Sex Differences in the Relation Between Supervision and Injury Risk Across Motor Development Stages: Transitioning From Infancy Into Toddlerhood
Authors: Morrongiello Barbara A , Corbett Michael , Bryant, MA Lindsay , Cox, MA Amanda 
Published: January 2022

Abstract

Rationale
Addressing a notable gap in research on injuries during infancy, this longitudinal study examined sex differences in the relationship between parents’ typical levels of supervision and infants’ injuries across motor development stages.

Method
Parents were recruited and completed biweekly phone calls about their infant’s motor skills. Once the infant was able to sit up independently, then a home visit was scheduled. Applying a participant-event monitoring method, parents were taught to complete diary forms (injury, supervision), which they started doing once the child could move from their seated location on the floor in some way (e.g., roll, crawl). Recordings continued until a month after the child could walk independently. Data (injury, supervision) were averaged within each motor development stage (low, high), and associations across stages were examined.

Results
Model testing indicated that supervision level moderated the relation between injury rate across motor development stages, but the strength of this association varied by sex of the child. More intense supervision predicted lower injury rates for girls more so than for boys.

Conclusions
Although the emergence of motor milestones has been associated with increased risk of injury during infancy, the current findings indicate that greater supervision can reduce this risk. However, supervision alone is not as effective to moderate injury risk for boys as it is for girls. Thus, for boys, additional strategies (e.g., hazard removal) may also be warranted to maximize reduction in their risk of injury as they acquire increasing motor skills.
FRAGILE CULM 18 encodes a UDP-glucuronic acid decarboxylase required for xylan biosynthesis and plant growth in rice
Authors: Ruan Nan , Dang Zhengjun , Wang Meihan , Cao Liyu , Wang Ye , Liu Sitong , Tang Yijun , Huang Yuwei , Zhang Qun , Xu Quan , Chen Wenfu , Li Fengcheng 
Published: January 2022

Abstract
Although UDP-glucuronic acid decarboxylases (UXSs) have been well studied with regard to catalysing the conversion of UDP-glucuronic acid into UDP-xylose, their biological roles in grasses remain largely unknown. The rice (Oryza sativa) genome contains six UXSs, but none of them has been genetically characterized. Here, we reported on the characterization of a novel rice fragile culm mutant, fc18, which exhibited brittleness with altered cell wall and pleiotropic defects in growth. Map-based cloning and transgenic analyses revealed that the FC18 gene encodes a cytosol-localized OsUXS3 and is widely expressed with higher expression in xylan-rich tissues. Monosaccharide analysis showed that the xylose level was decreased in fc18, and cell wall fraction determinations confirmed that the xylan content in fc18 was lower, suggesting that UDP-xylose from FC18 participates in xylan biosynthesis. Moreover, the fc18 mutant displayed defective cellulose properties, which led to an enhancement in biomass saccharification. Furthermore, expression of genes involved in sugar metabolism and phytohormone signal transduction was largely altered in fc18. Consistent with this, the fc18 mutant exhibited significantly reduced free auxin (indole-3-acetic acid) content and lower expression levels of PIN family genes compared with wild type. Our work reveals the physiological roles of FC18/UXS3 in xylan biosynthesis, cellulose deposition, and plant growth in rice.
Towards understanding inner nuclear membrane protein degradation in plants
Authors: Calvanese Enrico , Gu Yangnan 
Published: January 2022

AbstractThe inner nuclear membrane (INM) hosts a unique set of membrane proteins that play essential roles in various aspects of the nuclear function. However, overaccumulation or malfunction of INM protein has been associated with a range of rare genetic diseases; therefore, maintaining the homeostasis and integrity of INM proteins by active removal of aberrantly accumulated proteins and replacing defective molecules through proteolysis is of critical importance. Within the last decade, it has been shown that INM proteins are degraded in yeasts by a process very similar to endoplasmic reticulum-associated degradation (ERAD), which is accomplished by retrotranslocation of membrane substrates followed by proteasome-dependent proteolysis, and this process was named inner nuclear membrane-associated degradation (INMAD). INMAD is distinguished from ERAD by specific INM-localized E3 ubiquitin ligases and proteolysis regulators. While much is yet to be determined about the INMAD pathway in yeasts, virtually no knowledge of it exists for higher eukaryotes, and only very recently have several critical regulators that participate in INM protein degradation been discovered in plants. Here, we review key molecular components of the INMAD pathway and draw parallels between the yeast and plant system to discuss promising directions in the future study of the plant INMAD process.
A quantitative analysis of temperature-dependent seasonal dormancy cycling in buried Arabidopsis thaliana seeds can predict seedling emergence in a global warming scenario
Authors: Batlla Diego , Malavert Cristian , Farnocchia Rocío Belén Fernández , Footitt Steven , Benech-Arnold Roberto Luis , Finch-Savage William E 
Published: January 2022

Abstract
Understanding how the environment regulates seed-bank dormancy changes is essential for forecasting seedling emergence in actual and future climatic scenarios, and to interpret studies of dormancy mechanisms at physiological and molecular levels. Here, we used a population threshold modelling approach to analyse dormancy changes through variations in the thermal range permissive for germination in buried seeds of Arabidopsis thaliana Cvi, a winter annual ecotype. Results showed that changes in dormancy level were mainly associated with variations in the higher limit of the thermal range permissive for germination. Changes in this limit were positively related to soil temperature during dormancy release and induction, and could be predicted using thermal time. From this, we developed a temperature-driven simulation to predict the fraction of the seed bank able to germinate in a realistic global warming scenario that approximated seedling emergence timing. Simulations predicted, in accordance with seedling emergence observed in the field, an increase in the fraction of the seed bank able to emerge as a result of global warming. In addition, our results suggest that buried seeds perceive changes in the variability of the mean daily soil temperature as the signal to change between dormancy release and induction according to the seasons.
Jasmonate regulates seed dormancy in wheat via modulating the balance between gibberellin and abscisic acid
Authors: Nguyen Tran-Nguyen , Tuan Pham Anh , Ayele Belay T 
Published: January 2022

Abstract
Jasmonate (JA) regulates seed dormancy and germination; however, the underlying mechanisms remain poorly understood. Furthermore, it is unclear if JA is an essential regulator of dormancy and germination. We investigated whether the role of JA in regulating seed dormancy in wheat (Triticum aestivum L.) is mediated by modulation of gibberellin (GA)/abscisic acid (ABA) balance and if the reciprocal modulation of JA level and sensitivity is required for GA-mediated dormancy loss using physiological, pharmacological, and targeted transcriptomic and metabolomic approaches. JA-induced dormancy release in wheat seeds was associated with no change in GA level but up-regulation of GA signaling and ABA catabolism genes, and reduction of the ABA level. Although JA did not affect the expression levels of ABA signaling genes, up-regulation of germination-associated genes indicates a contribution of reduced ABA sensitivity to dormancy release. After-ripening-mediated dormancy loss was also associated with JA–GA synergistic and JA–ABA antagonistic interplays. The prevalence of no effect of GA, which effectively broke dormancy, on the JA-Ile level and expression patterns of JA biosynthesis/signaling and responsive genes reflects that GA-mediated dormancy release occurs independently of JA. Our study concludes that JA induces seed dormancy release in wheat via modulating ABA/GA balance; however, JA is not an essential regulator of dormancy and germination.
Investigation of Cases (III)
Authors: Sauer Ralf , Blanco Luis Ortiz 
Published: January 2022

Abstract
This chapter describes inspections. The European Commission enjoys ‘considerable room for manoeuvre’ in deciding whether an inspection is warranted and is entitled in each case to choose among the various means of investigation, irrespective of its approach with respect to other undertakings. Article 20(1) of Regulation 1/2003 grants the Commission powers to conduct ‘all necessary inspections’ of undertakings. This concerns investigations at the undertaking's premises, land, and means of transport. Although the powers of inspection pursuant to Regulation 1/2003 are very similar to those stipulated in Article 14 of Regulation 17, there are a number of significant extensions, including the power to carry out inspections on domestic property. In addition, Regulation 1/2003 incorporates some of the case law on inspections developed under Regulation 17. According to Article 20(2), inspectors may examine the books and other records related to the business, ‘irrespective of the medium on which they are stored’. This and the related power ‘to take or obtain in any form copies of or extracts from’ such records provides the Commission with a legal basis allowing it to search and copy electronic data. The Commission is also entitled to seal any business premises and books or records for the period and to the extent necessary for the inspection, and to ask any representative or member of staff of the undertaking for explanations on facts or documents relating to the subject matter and purpose of the inspection and to record the answers.