bluuebunny/crossref_metadata_2025_split huggingface dataset:
Indications for Lumbar Fusion in the Skeletally Mature Adolescent: How to Address Oblique Takeoff and Limb Length Discrepancy
Authors: Li Ying , Fletcher Nicholas D. 
Published: June 2021

Background:
Indications for posterior spinal fusion (PSF) with segmental spinal instrumentation (SSI) of a scoliotic deformity in a skeletally mature individual are based on the balance between the anticipated benefit of stopping future curve progression and the potential downside of loss of spinal mobility. The dilemma regarding PSF with SSI in the adolescent population is exacerbated by the patient’s participation in athletics requiring flexibility and motion of the spine, the location of the curve, the presence of pelvic obliquity, and the impact of a limb length discrepancy. The purpose of this review is to discuss the potential advantages and disadvantages of PSF with SSI in a hypothetical skeletally mature adolescent with a 45-degree lumbar curve, pelvic obliquity, and limb length discrepancy.

Discussion:
Natural history studies of untreated adolescent idiopathic scoliosis (AIS) have shown that slow curve progression throughout adulthood is likely. Adults with untreated AIS may also have more back pain and dissatisfaction with their appearance. Although the clinical and radiographic outcomes of PSF with SSI are excellent, patients should be counseled about the impact of fusing the lumbar spine on back pain, decreased spinal mobility, and potential inability to return to athletics at the same level. Adults who undergo surgery for AIS have greater operative morbidity and number of levels fused compared with adolescents.

Conclusion:
These factors should be presented when discussing observation versus PSF with SSI with patients and families. Delaying surgery until formal athletic participation is complete should be considered.
Streamlining Postoperative Care After Pediatric Supracondylar Humerus Fractures: Is Follow-up After Pin Removal Routinely Needed?
Authors: Patel Harshadkumar A. , Chaudhry Sonia , Lee Mark C. , Solomito Matthew 
Published: June 2021

Background:
Closed reduction and percutaneous pinning is the standard of care for displaced supracondylar humerus fractures (SCHFs). Although the operative management of SCHFs has achieved good consensus with low complication rates, there remains a paucity of literature on postoperative management. We hypothesized that routine office visits after pin removal can safely be avoided in uncomplicated SCHFs without compromising patient care.

Method:
A retrospective review was conducted to query the electronic medical record for SCHFs, treated with closed reduction and percutaneous pinning. Patients with complicated SCHFs were excluded. Patients were divided into 2 cohorts: follow-up (FU) and nonfollow-up (NFU), depending on the presence or absence of after-pin removal (APR) FU visits. Demographics, surgical variables, number of x-rays, referrals for physical therapy, total FU visits, complications, and clinical events after pin removal up to 3 months were compared. Subgroup analysis was performed according to Gartland fracture types.

Results:
A total of 179 patients were included in the study, 111 in the FU group and 68 in the NFU group. There were no significant differences found in demographics between the 2 groups. There were no significant differences in complications and APR clinical events between 2 groups (P>0.05). An average of 1.98 additional x-rays were taken APR in FU group. None of the NFU group patients required physical therapy. Excluding patients with pin site infections, 15/108 (13.9%) of FU group patients had >1 APR visits.

Summary:
For operatively managed uncomplicated SCHFs, patients who do not have routinely scheduled FU APR have no greater incidence of clinical events APR than patients with a scheduled FU. With a detailed discussion including expectations, timeframe for resuming activities, home exercises, and reassurance of the ease of FU if desired, routine FU APR can be safely eliminated after uncomplicated SCHFs in order to streamline postoperative care.

Level of Evidence:
Level III.
‘Cooperative game’ inspired approach for multi-area power system security management taking advantage of grid flexibilities
Authors: Karangelos Efthymios , Panciatici Patrick 
Published: June 2021

This paper advocates for a progressive rethinking of the day-ahead/intra-day power system security management practice in the low-carbon energy transition era. As a starting point, the need for coordination between multi-area transmission system operators in order to efficiently exploit the value of grid flexibility towards operating the low-carbon, multi-area power system securely and economically is emphasized. On this basis, the core proposal of this paper is the adoption of a new approach to day-ahead/intra-day multi-area power system security management, inspired by the principles of cooperative game theory. The proposed approach relies on counterfactual analysis to evaluate the (positive and/or negative) impact of each distinctive control area to the common security of the multi-area system, thus providing clear economic incentives to achieve the required coordination. This proposal is not a marginal approach and notably facilitates the integration of more detailed physical modelling (including the non-convexities of the power system) in the inter-TSO settlement of the multi-area interconnected system security management cost. The proposed framework allows some level of subsidiarity and the definition of hedging products to cover ex-post costs. Further from the blueprint of the proposed approach, the paper presents a demonstrative implementation in the context of static N-1 security management and discusses prominent research and development pathways in order to progressively put such vision into practice.This article is part of the theme issue ‘The mathematics of energy systems’.
On incorporating forecasts into linear state space model Markov decision processes
Authors: de Chalendar Jacques A. , Glynn Peter W. 
Published: June 2021

Weather forecast information will very likely find increasing application in the control of future energy systems. In this paper, we introduce an augmented state space model formulation with linear dynamics, within which one can incorporate forecast information that is dynamically revealed alongside the evolution of the underlying state variable. We use the martingale model for forecast evolution (MMFE) to enforce the necessary consistency properties that must govern the joint evolution of forecasts with the underlying state. The formulation also generates jointly Markovian dynamics that give rise to Markov decision processes (MDPs) that remain computationally tractable. This paper is the first to enforce MMFE consistency requirements within an MDP formulation that preserves tractability.
This article is part of the theme issue ‘The mathematics of energy systems’.
An econometric model for intraday electricity trading
Authors: Kremer Marcel , Kiesel Rüdiger , Paraschiv Florentina 
Published: June 2021

This paper develops an econometric price model with fundamental impacts for intraday electricity markets of 15-min contracts. A unique dataset of intradaily updated forecasts of renewable power generation is analysed. We use a threshold regression model to examine how 15-min intraday trading depends on the slope of the merit order curve. Our estimation results reveal strong evidence of mean reversion in the price formation mechanism of 15-min contracts. Additionally, prices of neighbouring contracts exhibit strong explanatory power and a positive impact on prices of a given contract. We observe an asymmetric effect of renewable forecast changes on intraday prices depending on the merit-order-curve slope. In general, renewable forecasts have a higher explanatory power at noon than in the morning and evening, but price information is the main driver of 15-min intraday trading.
This article is part of the theme issue ‘The mathematics of energy systems’.
Evolutionary tracking of cancer haplotypes at single-cell resolution
Authors: Williams Marc J , Funnell Tyler , O’Flanagan Ciara H , McPherson Andrew , Salehi Sohrab , Vázquez-García Ignacio , Kabeer Farhia , Lee Hakwoo , Masud Tehmina , Eirew Peter , Yap Damian , Wang Beixi , Brimhall Jazmine , Biele Justina , Ting Jerome , Beatty Sean , Lai Daniel , Pham Jenifer , Grewal Diljot , Abrams Douglas , Havasov Eliyahu , Leung Samantha , Bojilova Viktoria , Weiner Adam C , Rusk Nicole , Uhlitz Florian , Ceglia Nicholas ,   IMAXT consortium, Aparicio Samuel , Shah Sohrab P. 
Published: June 2021

AbstractCancer genomes exhibit extensive chromosomal copy number changes and structural variation, yet how allele specific alterations drive cancer genome evolution remains unclear. Here, through application of a new computational approach we report allele specific copy number alterations in 11,097 single cell whole genomes from genetically engineered mammary epithelial cells and 21,852 cells from high grade serous ovarian and triple negative breast cancers. Resolving single cell copy number profiles to individual alleles uncovered genomic background distributions of gains, losses and loss of heterozygosity, yielding evidence of positive selection of specific chromosomal alterations. In addition specific genomic loci in maternal and paternal alleles were commonly found to be altered in parallel with convergent phenotypic transcriptional effects. Finally we show that haplotype specific alterations trace the cyclical etiology of high level amplifications and reveal clonal haplotype decomposition of complex structures. Together, our results illuminate how allele and haplotype specific alterations, here determined across thousands of single cell cancer genomes, impact the etiology and evolution of structural variations in human tumours.
Single-cell RNA-sequencing reveals widespread personalized, context-specific gene expression regulation in immune cells
Authors: Oelen Roy , de Vries Dylan H. , Brugge Harm , Gordon Gracie , Vochteloo Martijn ,   BIOS Consortium, Ye Chun J. , Westra Harm-Jan , Franke Lude , van der Wijst Monique G.P. 
Published: June 2021

AbstractGene expression and its regulation can be context-dependent. To dissect this, using samples from 120 individuals, we single-cell RNA-sequenced 1.3M peripheral blood mononuclear cells exposed to three different pathogens at two time points or left unexposed. This revealed thousands of cell type-specific expression changes (eQTLs) and pathogen-induced expression changes (response QTLs) that are influenced by genetic variation. In monocytes, the strongest responder to pathogen stimulations, genetics also affected co-expression of 71.4% of these eQTL genes. For example, the pathogen recognition receptor CLEC12A showed many such co-expression interactions, but only in monocytes after 3h pathogen stimulation. Further analysis linked this to interferon-regulating transcription factors, a finding that we recapitulated in an independent cohort of patients with systemic lupus erythematosus, a condition characterized by increased interferon activity. Altogether, this study highlights the importance of context for gaining a better understanding of the mechanisms of gene regulation in health and disease.
Differentiation of Peritubular Myoid-Like Cells from Human Induced Pluripotent Stem Cells
Authors: Robinson Meghan , Witherspoon Luke , Willerth Stephanie , Flannigan Ryan 
Published: June 2021

ABSTRACTSpermatogenesis is a complex process requiring intricate cellular interactions between multiple cell types to produce viable sperm. Peritubular myoid cells (PTMs) are smooth muscle cells that line the seminiferous tubules and play a critical role in sperm production by providing mechanical support and molecular signaling factors. In vitro investigation of their contribution to spermatogenesis and their dysfunction in infertility is currently limited by the rare accessibility of human testicular tissue for research. Therefore, this study set forth to generate an alternative source of PTMs using human induced pluripotent stem cells (hiPSCs) - adult cells that have been reprogrammed into a pluripotent state, making them capable of indefinite expansion and the regeneration of any cell type in the body. PTMs and Leydig cells arise from a common progenitor, so we hypothesized that PTMs could be derived by modifying an existing differentiation protocol for Leydig cell differentiation from hiPSCs. These hiPSC-derived cells, or hPTMs, were characterized and compared to hiPSC-derived Leydig cells (hLCs) and human primary Sertoli cells as a negative control. Our findings show that the substitution of the molecular patterning factor Platelet-Derived Growth Factor Subunit B (PDGF-BB) for Platelet-Derived Growth Factor Subunit A (PDGF-AA) in a molecule-based differentiation protocol for deriving Leydig-like cells, is sufficient to derive peritubular myoid-like cells. This study describes a method for generating PTM-like cells from hiPSCs. These cells will allow for ongoing understanding of the cellular interactions required for normal spermatogenesis in an in vitro setting.
Self-reported adaptability among postgraduate dental learners and their instructors: accelerated change induced by COVID-19
Authors: Otaki Farah , Amir-Rad Fatemeh , Al-Halabi Manal , Baqain Zaid , Zary Nabil 
Published: June 2021

AbstractIt is forecasted that the skills and competencies necessary for post-pandemic success in higher education need to be founded upon adaptability, coping, and Self-regulated Learning (SRL). It is worth investigating how stakeholders perceived their adaptability and coping with the accelerated change accompanying COVID-19. Accordingly, the purpose of this study was to assess the self-reported adaptability of postgraduate dental learners and their instructors in the context of abrupt transition to distance learning induced by the pandemic.This study utilized a convergent mixed methods study design. The qualitative and quantitative data were concurrently collected from instructors and learners. The datasets were analyzed independently, and the generated information was integrated using a joint model analysis.The percentage of average of self-reported adaptability of both groups was 81.15%. The instructors, with a mean of satisfaction of 17.94 (±1.76), rated their adaptability significantly higher than the learners, with a mean of satisfaction of 15.66 (±2.77) (p=0.002). The thematic analysis resulted in two interrelated themes: Self and Environment. Within the Self theme, three subthemes surfaced: Cognitions, Emotions, Behaviors. As for the Environment theme, it encapsulated two subthemes: Enablers and Impediments.The stakeholders perceived themselves to have adapted well to the transition, and SRL appeared as a cornerstone in the adaptation to the accelerated change (accompanying COVID-19). There appeared to be an interplay between the cognitions, emotions, and behaviors on the level of the self as part of the adaptation process. Also, building upon existent models of SRL, this study uncovered that the stakeholders considered the environment to play a crucial role in their adaptation process. This highlights the importance of developing a climate that remains, despite external pressures, conducive to attaining learning and teaching goals. It is also crucial for university-level mental health promotion activities to proactively foster, among learners and instructors, adaptability, building ‘academic resilience’.
Epitope-Based Peptide prediction of vaccine against European bat lyssaviruses type 2 Glycoprotein G with Immunoinformatic Approach
Authors: Gumaa Manal A. , Idris Abeer Babiker , Bashir H. , Dawoud Enas dk. , Lina Elhassn. , Hassan Mohamed A. 
Published: June 2021

AbstractObjectiveEuropean bat lyssaviruses (EBLV) type 2 is present in many European countries. Infection is usually seen in bats, the primary reservoirs of the viruses. Human deaths have been documented within few days following bat exposures. So, it is very useful to design an insilco peptide vaccine for European bat lyssaviruses type 2 virus using glycoprotein G as an immunogen to stimulate protective immune responseResultsB cell tests were conducted for Bepipred with 15 conserved epitopes, Emini surface accessibility prediction with 7 conserved epitopes in the surface and Kolaskar and Tongaonkar antigenicity tested with three conserved epitopes being antigenic. 357 conserved epitopes were predicted to interact with different MHC-1 alleles with (IC50) ≤500 while 282 conserved epitopes found to interact with MHC-II alleles with IC50≤ 1000. Among all tested epitopes for world population coverage the epitope VFSYMELKV binding to MHC11 alleles was 97.94% and it found to bind 10 different alleles that indicate strong potential to formulate peptide vaccine for lyssaviruses type 2 virus. To the best of our knowledge this is the first study to propose peptide vaccine for European bat lyssavirus type 2.
Postnatal lymph node expansion of stromal progenitors towards reticular and CD34+stromal cell subsets is determined by distinct transcriptional programs
Authors: Pezoldt Joern , Wiechers Carolin , Litovchenko Maria , Biocanin Marjan , Zou Mangge , Sitnik Katarzyna , Beckstette Michael , Chen Wanze , Gardeux Vincent , Floess Stefan , Ebel Maria , Russeil Julie , Arampatzi Panagiota , Vafardanejad Ehsan , Saliba Antoine-Emmanuel , Deplancke Bart , Huehn Jochen 
Published: June 2021

AbstractGut-draining mesenteric lymph nodes (mLN) provide the framework and microenvironment to shape intestinal adaptive immune responses. We previously delineated transcriptional signatures in LN stromal cells (SC), pointing to tissue-specific variability in composition and immuno-modulatory function of SCs.Here, we dissect the tissue-specific epigenomic DNA accessibility and CpG methylation landscape of LN non-endothelial SCs and identify a microbiota-independent core epigenomic signature of LN SCs. By combined analysis of transcription factor (TF) binding sites together with the gene expression profiles of non-endothelial SCs, we delineated TFs poising skin-draining peripheral LN (pLN) SCs for pro-inflammatory responses. Furthermore, using scRNA-seq, we dissected the developmental trajectory of mLN SCs derived from postnatal to aged mice, identifying two distinct putative progenitors, namely CD34+SC and fibroblastic reticular stromal cell (FRC) progenitors, which both feed the rapid postnatal LN expansion. Finally, we identifiedIrf3as a key differentiation TF inferred from the epigenomic signature of mLN SCs that is dynamically expressed along the differentiation trajectories of FRCs, and validatedIrf3as a regulator of Cxcl9+FRC differentiation.Together, our data constitute a comprehensive transcriptional and epigenomic map of mLN development and dissect location-specific, microbiota-independent properties of mLN non-endothelial SCs. As such, our findings represent a valuable resource to identify core transcriptional regulators that impinge on the developing mLN early in life, thereby shaping long-lasting intestinal adaptive immune responses.
In-depth sequence-function characterization reveals multiple paths to enhance phenylalanine ammonia-lyase (PAL) activity
Authors: Trivedi Vikas D. , Chappell Todd C. , Krishna Naveen B. , Shetty Anuj , Sigamani Gladstone G. , Mohan Karishma , Ramesh Athreya , R. Pravin Kumar , Nair Nikhil U. 
Published: June 2021

ABSTRACTPhenylalanine ammonia-lyases (PALs) deaminate L-phenylalanine to trans-cinnamic acid and ammonium and have idespread application in chemo-enzymatic synthesis, agriculture, and medicine. In particular, the PAL from Anabaena variabilis (Trichormus variabilis) has garnered significant attention as the active ingredient in Pegvaliase®, the only FDA-approved drug treating classical phenylketonuria (PKU). Although an extensive body of literature exists on structure, substrate-specificity, and catalytic mechanism, protein-wide sequence determinants of function remain unknown, which limits the ability to rationally engineer these enzymes. Previously, we developed a high-throughput screen (HTS) for PAL, and here, we leverage it to create a detailed sequence-function landscape of PAL by performing deep mutational scanning (DMS). Our method revealed 79 hotspots that affected a positive change in enzyme fitness, many of which have not been reported previously. Using fitness values and structure-function analysis, we picked a subset of residues for comprehensive single- and multi-site saturation mutagenesis to improve the catalytic activity of PAL and identified combinations of mutations that led to improvement in reaction kinetics in cell-free and cellular contexts. To understand the mechanistic role of the most beneficial mutations, we performed QM/MM and MD and observed that different mutants confer improved catalytic activity via different mechanisms, including stabilizing first transition and intermediate states and improving substrate diffusion into the active site, and decreased product inhibition. Thus, this work provides a comprehensive sequence-function relationship for PAL, identifies positions that improve PAL activity when mutated and assesses their mechanisms of action.
Linking parasitism to network centrality and the impact of sampling bias in its interpretation
Authors: Xu Zhihong , MacIntosh Andrew J. J. , Castellano-Navarro Alba , Macanás-Martínez Emilio , Suzumura Takafumi , Duboscq Julie 
Published: June 2021

AbstractGroup living is beneficial for individuals, but also comes with costs. One such cost is the increased possibility of pathogen transmission because increased numbers or frequencies of social contacts are often associated with increased parasite abundance or diversity. The social structure of a group or population is paramount to patterns of infection and transmission. Yet, for various reasons, studies investigating the links between sociality and parasitism in animals, especially in primates, have only accounted for parts of the group (e.g., only adults), which is likely to impact the interpretation of results. Here, we investigated the relationship between social network centrality and an estimate of gastrointestinal helminth infection intensity in a whole group of Japanese macaques (Macaca fuscata). We then tested the impact of omitting parts of the group on this relationship. We aimed to test: (1) whether social network centrality – in terms of the number of partners (degree), frequency of interactions (strength), and level of social integration (eigenvector) – was linked to parasite infection intensity (estimated by eggs per gram of faeces, EPG); and, (2) to what extent excluding portions of individuals within the group might influence the observed relationship. We conducted social network analysis on data collected from one group of Japanese macaques over three months on Koshima Island, Japan. We then ran a series of knock-out simulations. General linear mixed models showed that, at the whole-group level, network centrality was positively associated with geohelminth infection intensity. However, in partial networks with only adult females, only juveniles, or random subsets of the group, the strength of this relationship - albeit still generally positive - lost statistical significance. Furthermore, knock-out simulations where individuals were removed but network metrics were retained from the original whole-group network showed that these changes are partly a power issue and partly an effect of sampling the incomplete network. Our study indicates that sampling bias can thus hamper our ability to detect real network effects involving social interaction and parasitism. In addition to supporting earlier results linking geohelminth infection to Japanese macaque social networks, this work introduces important methodological considerations for research into the dynamics of social transmission, with implications for infectious disease epidemiology, population management, and health interventions.