bluuebunny/crossref_metadata_2025_split huggingface dataset:
Frameshift mutation (690delG) in cpxA contributes to the extensive drug resistance of a Serratia marcescens clinical isolate
Authors: Gravrand Victor , Ariey Frédéric , Terracol Laura , Poupet Hélène , Doloy Alexandra , Poyart Claire , Mammeri Hedi 
Published: March 2022

Abstract

Objectives
To identify the genetic change responsible for resistance to penicillins, extended-spectrum cephalosporins (ESCs), aminoglycosides and ciprofloxacin in a Serratia marcescens clinical isolate recovered from a pancreatic abscess 6 weeks after a WT strain was isolated from the same patient. The impact on the fitness was also assessed.

Methods
The genomes of both S. marcescens isolates were sequenced using Illumina technology, assembled, annotated and compared with each other. PCR amplification followed by Sanger sequencing was carried out to confirm the mutation. Complementation of the resistant isolate with a recombinant plasmid harbouring the WT gene was performed. The growth rates were measured for both isolates in LB medium.

Results
Comparative genomic analysis disclosed only one frameshift mutation (690delG) in the cpxA gene, which codes for the histidine kinase of a two-component system (TCS). This change introduced a premature termination codon, leading to the truncated CpxA_HatR variant that contained 234 amino acids instead of 464. Complementation, which consisted of transfer of the WT cpxA into the resistant S. marcescens derivative, restored completely its susceptibility to ESCs, aminoglycosides and ciprofloxacin, thus confirming the contribution of the CpxA_HatR variant to resistance. Growth analysis showed that the fitness of the resistant isolate was unchanged.

Conclusions
This study shows for the first time that constitutive activation of the Cpx pathway can per se confer resistance to ESCs and ciprofloxacin, in addition to the aminoglycoside resistance usually described. It sheds new light on the role of altered TCSs in fostering bacterial survival.
Implementation of a data control framework to ensure confidentiality, integrity, and availability of high-quality real-world data (RWD) in the NeuroTransData (NTD) registry
Authors: Wehrle Knut , Tozzi Viola , Braune Stefan , Roßnagel Fabian , Dikow Heidi , Paddock Silvia , Bergmann Arnfin , van Hövell Philip 
Published: March 2022

Abstract

Objective
To implement a dynamic data management and control framework that meets the multiple demands of high data quality, rigorous information technology security, and flexibility to continuously incorporate new methodology for a large disease registry.

Materials and Methods
Guided by relevant sections of the COBIT framework and ISO 27001 standard, we created a data control framework supporting high-quality real-world data (RWD) studies in multiple disease areas. We first mapped and described the entire data journey and identified potential risks for data loss or inconsistencies. Based on this map, we implemented a control framework adhering to best practices and tested its effectiveness through an analysis of random data samples. An internal strategy board was set up to regularly identify and implement potential improvements.

Results
We herein describe the implementation of a data management and control framework for multiple sclerosis, one disease area in the NeuroTransData (NTD) registry that exemplifies the dynamic needs for high-quality RWD analysis. Regular manual and automated analysis of random data samples at multiple checkpoints guided the development and implementation of the framework and continue to ensure timely identification of potential threats to data accuracy.

Discussion and conclusions
High-quality RWD, especially those derived from long-term disease registries, are of increasing importance from regulatory and reimbursement perspectives, requiring owners to provide data of comparable quality to clinical trials. The framework presented herein responds to the call for transparency in real-world analyses and allows doctors and patients to experience an immediate benefit of the collected data for individualized optimal care.
Combining frog-leg lateral view may serve as a more sensitive X-ray position in monitoring collapse in osteonecrosis of the femoral head
Authors: Wei Qiu-Shi , He Min-Cong , He Xiao-Ming , Lin Tian-Ye , Yang Peng , Chen Zhen-Qiu , Zhang Qing-Wen , He Wei 
Published: March 2022

ABSTRACT
Load-bearing capacity of the bone structures of anterolateral weight-bearing area plays an important role in the progressive collapse in osteonecrosis of the femoral head (ONFH). The purpose of this study is to assess the efficacy of combined evaluation of anteroposterior (AP) and frog-leg lateral (FLL) view in diagnosing collapse. Between December 2016 and August 2018, a total of 478 hips from 372 patients with ONFH (268 male, 104 female; mean age 37.9 ± 11.4 years) were retrospectively evaluated. All patients received standard AP and FLL views of hip joints. Japanese Investigation Committee (JIC) classification system was used to classify necrotic lesion in AP view. Anterior necrotic lesion was evaluated by FLL view. All patients with pre-collapse ONFH underwent non-operative hip-preserving therapy. The collapse rates were calculated and compared with Kaplan–Meier survival analysis with radiological collapse as endpoints. Forty-four (44/478, 9.2%) hips were classified as type A, 65 (65/478, 13.6%) as type B, 232 (232/478, 48.5%) as type C1 and 137 (137/478, 28.7%) as type C2. Three hundred cases (300/478, 62.5%) were collapsed at the initial time point. Two hundred and twenty six (226/300, 75.3%) hips and 298 (298/300, 99.3%) hips collapse were identified with AP view and FLL view, respectively. An average follow-up of 37.0 ± 32.0 months was conducted to evaluate the occurrence of collapse in 178 pre-collapse hips. Collapses occurred in 89 hips (50.0%). Seventy-seven (77/89, 86.5%) hips were determined with AP view alone and 85 (85/89, 95.5%) hips were determined with the combination of AP and FLL views. The collapse rates at five years were reported as 0% and 0%, 16.2% and 24.3%, 58.3% and 68.1% and 100% and 100% according to AP view alone or combination of AP and FLL views for types A, B, C1 and C2, respectively. The collapse can be diagnosed more accurately by combination of AP and FLL views. Besides, JIC type A and type B ONFH can be treated with conservative hip preservation, but pre-collapse type C2 ONFH should be treated with joint-preserving surgery. Type C1 needs further study to determine which subtype has potential risk of collapse.
Bringing PROMIS to Early Childhood: Introduction and Qualitative Methods for the Development of Early Childhood Parent Report Instruments
Authors: Cella David , Blackwell Courtney K , Wakschlag Lauren S 
Published: March 2022

Abstract

Objective
Provide an overview of the Patient-Reported Outcomes Measurement Information System (PROMIS®) Early Childhood Parent Report measurement development project and describe its qualitative methods.

Methods
The PROMIS Early Childhood (PROMIS EC) initiative used the PROMIS mixed-methods approach to patient-reported outcome development, with insight from the developmental specification framework to create parent report measures appropriate for assessing young children’s health-related quality of life. Qualitative methods to develop these instruments included expert input, literature and measure review, and parent concept elicitation and cognitive interviews to confirm the measure frameworks, item understandability, and developmental appropriateness.

Results
Twelve measures resulted from the PROMIS EC initiative. These parent report instruments cover young children’s physical, mental, and social health.

Conclusions
The new PROMIS EC Parent Report instruments offer clinicians and researchers brief and psychometrically robust tools to evaluate young children’s physical, mental, and social health outcomes. Aligned with the PROMIS Pediatric instruments, the early childhood versions enable coherent lifespan measurement starting at age 1 while maintaining developmental sensitivity.
Measuring PROMIS® Physical Activity and Sleep Problems in Early Childhood
Authors: Lai Jin-Shei , Blackwell Courtney K , Tucker Carole A , Jensen Sally E , Cella David 
Published: March 2022

Abstract

Objective
Physical activity (PA) and sleep are leading health indicators for individuals of all ages. Monitoring young children’s PA and sleep using psychometrically sound instruments could help facilitate timely interventions to promote healthy development. This article describes the development of the PROMIS® Early Childhood (EC) Parent Report Physical Activity (PA) and Sleep Problems (SP) measures for children aged 1–5 years.

Methods
Item pools were generated by interviewing parents, input from content experts, and literature review. Data from a U.S. general population sample were used to determine factor structures of item pools via factor analytic approaches, estimate item parameters via item response theory (IRT) models, and establish norms. Pearson correlations were used to evaluate across-domain associations. Analysis of variance was used and known-groups’ validity of PA and SP by comparing their scores to PROMIS EC Parent Report Global Health: child’s physical, emotional, and mental conditions.

Results
Initial item pools consisted of 19 and 26 items for PA and SP, respectively. Factor analyses’ results supported unidimensionality of 5 and 16 items measuring PA and SP, respectively, which were then calibrated using IRT. Norms were established by centering to a probability-based U.S. general population. Computerized adaptive testing algorithms were established. Some analyses supported initial measure validity.

Conclusions
The PROMIS EC PA calibrated scale and SP item banks are user-friendly and brief, yet produce precise scores. Both measures enable psychometrically sound assessment of PA behavior and sleep problems. Future studies to comprehensively evaluate the validity of these two measures are warranted.
Measuring PROMIS® Well-Being in Early Childhood
Authors: Blackwell Courtney K , Kallen Michael A , Lai Jin-Shei , Bevans Katherine B , Wakschlag Lauren S , Cella David 
Published: March 2022

Abstract

Objective
Expand the current Patient-Reported Outcome Measurement Information System (PROMIS®) well-being measures to early childhood (1–5 years) using best practices from PROMIS and developmental science.

Methods
Qualitative methods included expert input, literature and measure review, and parent interviews to confirm measure frameworks, item understandability, and developmental appropriateness. Quantitative methods included two waves of field testing and item response theory (IRT)-based psychometric evaluation of reliability and validity, as well as IRT centering and item calibration. Correlational analyses with other PROMIS Early Childhood (EC) Parent Report measures and known-group differences analyses by health status were conducted to evaluate construct validity. All measures were normed to the general U.S. population.

Results
Qualitative results suggested three primary early childhood well-being domains: Positive Affect, Engagement, and Self-Regulation. Quantitative results revealed a unidimensional factor structure for Positive Affect and multidimensional factor structures for Engagement and Self-Regulation, both of which had two factors accounting for &gt;10% of modeled variance reflecting unique unidimensional domains. This resulted in five final PROMIS EC well-being measures: Positive Affect, Engagement—Curiosity, Engagement—Persistence, Self-Regulation—Flexibility, and Self-Regulation—Frustration Tolerance. Correlations and known-groups differences analyses showed robust construct validity across a range of chronic health conditions.

Conclusions
The new PROMIS EC Parent Report well-being measures offer clinicians and researchers a brief, efficient, and precise way to evaluate young children’s well-being. All five measures include only positively valanced item content, which pushes the field to evaluate the presence of children’s positive assets rather than the absence of problems.
Towards improved dynamic photosynthesis in C3 crops by utilizing natural genetic variation
Authors: Sakoda Kazuma , Adachi Shunsuke , Yamori Wataru , Tanaka Yu 
Published: March 2022

AbstractUnder field environments, fluctuating light conditions induce dynamic photosynthesis, which affects carbon gain by crop plants. Elucidating the natural genetic variations among untapped germplasm resources and their underlying mechanisms can provide an effective strategy to improve dynamic photosynthesis and, ultimately, improve crop yields through molecular breeding approaches. In this review, we first overview two processes affecting dynamic photosynthesis, namely (i) biochemical processes associated with CO2 fixation and photoprotection and (ii) gas diffusion processes from the atmosphere to the chloroplast stroma. Next, we review the intra- and interspecific variations in dynamic photosynthesis in relation to each of these two processes. It is suggested that plant adaptations to different hydrological environments underlie natural genetic variation explained by gas diffusion through stomata. This emphasizes the importance of the coordination of photosynthetic and stomatal dynamics to optimize the balance between carbon gain and water use efficiency under field environments. Finally, we discuss future challenges in improving dynamic photosynthesis by utilizing natural genetic variation. The forward genetic approach supported by high-throughput phenotyping should be introduced to evaluate the effects of genetic and environmental factors and their interactions on the natural variation in dynamic photosynthesis.
The cosmic web connection to the dark matter halo distribution through gravity
Authors: Kitaura F-S , Balaguera-Antolínez A , Sinigaglia F , Pellejero-Ibáñez M 
Published: March 2022

ABSTRACT
This work investigates the connection between the cosmic web and the halo distribution through the gravitational potential at the field level. We combine three fields of research, cosmic web classification, perturbation theory expansions of the halo bias, and halo (galaxy) mock catalogue making methods. In particular, we use the invariants of the tidal field and the velocity shear tensor as generating functions to reproduce the halo number counts of a reference catalogue from full gravity calculations, populating the dark matter field on a mesh well into the non-linear regime ($3\, h^{-1}\, {\rm Mpc}$ scales). Our results show an unprecedented agreement with the reference power spectrum within 1 per cent up to $k=0.72\, h\, {\rm Mpc}^{-1}$. By analysing the three-point statistics on large scales (configurations of up to $k=0.2\, h\, {\rm Mpc}^{-1}$), we find evidence for non-local bias at the 4.8σ confidence level, being compatible with the reference catalogue. In particular, we find that a detailed description of tidal anisotropic clustering on large scales is crucial to achieve this accuracy at the field level. These findings can be particularly important for the analysis of the next generation of galaxy surveys in mock galaxy production.
Ravel’s Octatonic Scripts
Authors: Blättler Damian 
Published: March 2022

AbstractThis article investigates the use of octatonic chord progressions at deeper structural levels in the music of Maurice Ravel. Octatonic chord progressions are successions of triads and seventh chords derived from a single octatonic collection that are incompatible with other scales. These are shown to form the foundation for large spans of music, even when their constituent chords are embellished with non-octatonic macroharmony; the Discrete Fourier Transform is used to distinguish between the octatonicity of an underlying progression and the various surface colors that adorn it. Deeper-level octatonic chord progressions are woven into the formal scripts of several of Ravel’s major compositions: the two piano concerti, the Violin Sonata, and the Rapsodie espagnole. In these pieces, long-range motion through octatonic progressions undergirds entire sections or movements, and interacts with other elements of the work to create dynamic formal processes.
Asymmetric information, strategic transfers, and the design of long-term care policies
Authors: Canta Chiara , Cremer Helmuth 
Published: March 2022

Abstract
We study the optimal design of social long-term care (LTC) insurance when the utility of informal caregivers is taken into account. Informal care is exchange-based. Children’s cost of providing care is continuously distributed over some interval and is not observable. Parents choose a rule specifying transfers conditional on the level of informal care. We study first uniform provision of LTC and then a nonlinear policy depending on family transfers. In both cases, informal care increases with the children’s welfare weight. Our theoretical analysis is completed by calibrated numerical solutions. Uniform public care should represent up to 40% of total care but its share decreases to about 30% as the weight of children increases. In the nonlinear case, public care increases with the children’s cost of providing care at a faster rate when children’s weight in social welfare is higher. It represents 100% of total care for families with high-cost children.
Detection of HIV Virologic Failure and Switch to Second-Line Therapy: A Systematic Review and Meta-analysis of Data From Sub-Saharan Africa
Authors: Bernabé Kerlly J , Siedner Mark , Tsai Alexander C , Marconi Vincent C , Murphy Richard A 
Published: March 2022

Abstract

Background
The late recognition of virologic failure (VF) places persons with HIV in Sub-Saharan Africa at risk for HIV transmission, disease progression, and death. We conducted a systematic review and meta-analysis to determine if the recognition and response to VF in the region has improved.

Methods
We searched for studies reporting CD4 count at confirmed VF or at switch to second-line antiretroviral therapy (ART). Using a random-effects metaregression model, we analyzed temporal trends in CD4 count at VF—or at second-line ART switch—over time. We also explored temporal trends in delay between VF and switch to second-line ART.

Results
We identified 26 studies enrolling patients with VF and 10 enrolling patients at second-line ART switch. For studies that enrolled patients at VF, pooled mean CD4 cell count at failure was 187 cells/mm3 (95% CI, 111 to 263). There was no significant change in CD4 count at confirmed failure over time (+4 cells/year; 95% CI, –7 to 15). Among studies that enrolled patients at second-line switch, the pooled mean CD4 count was 108 cells/mm3 (95% CI, 63 to 154). CD4 count at switch increased slightly over time (+10 CD4 cells/year; 95% CI, 2 to 19). During the same period, the mean delay between confirmation of VF and switch was 530 days, with no significant decline over time (–14 days/year; 95% CI, –58 to 52).

Conclusions
VF in Africa remains an event recognized late in HIV infection, a problem compounded by ongoing delays between VF and second-line switch.
Excellent Traits in Public Health: Virtuous Structures and the Structure of Virtue
Authors: Meagher Karen M 
Published: March 2022

AbstractMacKay’s Public Health Virtue Ethics offers a distinctive approach to public health ethics, with social structures at the forefront. MacKay’s helpful overview of the recent literature considers three distinct referents for ascribing virtues in public health ethics: (i) individuals, such as public health practitioners, (ii) social structures, such as public health institutions and policies and (iii) the communities affected by public health policy. While MacKay is interested in virtuous structures, I am interested in the structure of virtue as a precursor to this approach. In this commentary, I seek to unpack the structure of virtue itself, to delineate what various accounts of public health virtues offer, including MacKay’s new account. For such clarity, I turn to David Pears’ neo-Aristotelian essay on moral courage, in which he distinguishes external goals, internal goals and countergoals. Additional virtue vocabulary advances discussion of how the moral psychology of virtue traditions can be best adapted to public health professions, policy and practice.
Development and carotenoid synthesis in dark-grown carrot taproots require PHYTOCHROME RAPIDLY REGULATED1
Authors: Arias Daniela , Ortega Angélica , González-Calquin Christian , Quiroz Luis Felipe , Moreno-Romero Jordi , Martínez-García Jaime F , Stange Claudia 
Published: March 2022

Abstract
Light stimulates carotenoid synthesis in plants during photomorphogenesis through the expression of PHYTOENE SYNTHASE (PSY), a key gene in carotenoid biosynthesis. The orange carrot (Daucus carota) synthesizes and accumulates high amounts of carotenoids in the taproot that grows underground. Contrary to other organs, light impairs carrot taproot development and represses the expression of carotenogenic genes, such as DcPSY1 and DcPSY2, reducing carotenoid accumulation. By means of RNA sequencing, in a previous analysis, we observed that carrot PHYTOCHROME RAPIDLY REGULATED1 (DcPAR1) is more highly expressed in the underground grown taproot compared with those grown in light. PAR1 is a transcriptional cofactor with a negative role in shade avoidance syndrome regulation in Arabidopsis (Arabidopsis thaliana) through the dimerization with PHYTOCHROME-INTERACTING FACTORs (PIFs), allowing a moderate synthesis of carotenoids. Here, we show that overexpressing AtPAR1 in carrot increases carotenoid production in taproots grown underground as well as DcPSY1 expression. The high expression of AtPAR1 and DcPAR1 led us to hypothesize a functional role of DcPAR1 that was verified through in vivo binding to AtPIF7 and overexpression in Arabidopsis, where AtPSY expression and carotenoid accumulation increased together with a photomorphogenic phenotype. Finally, DcPAR1 antisense carrot lines presented a dramatic decrease in carotenoid levels and in relative expression of key carotenogenic genes as well as impaired taproot development. These results suggest that DcPAR1 is a key factor for secondary root development and carotenoid synthesis in carrot taproot grown underground.