bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evolving therapies, neurocognitive outcomes, and functional independence in adult survivors of childhood glioma
Authors: Papini Chiara , Mirzaei S. Sedigheh , Xing Mengqi , Tonning Olsson Ingrid , de Blank Peter M K , Lange Katharine R , Salloum Ralph , Srivastava Deokumar , Leisenring Wendy M , Howell Rebecca M , Oeffinger Kevin C , Robison Leslie L , Armstrong Gregory T , Krull Kevin R , Brinkman Tara M 
Published: September 2023

Abstract

Background
Treatment of childhood glioma has evolved to reduce radiotherapy exposure with the goal of limiting late toxicity. However, the associations between treatment changes and neurocognition, and the contribution of neurocognition and chronic health conditions to attainment of adult independence, remain unknown.

Methods
Adult survivors of childhood glioma diagnosed in 1970-1999 in the Childhood Cancer Survivor Study (n = 1284; median [minimum-maximum] 30 [18-51] years of age at assessment; 22 [15-34] years from diagnosis) self-reported neurocognitive impairment and chronic health conditions. Multivariable models evaluated associations between changes in treatment exposures (surgery only, chemotherapy [with or without surgery], cranial radiation [with or without chemotherapy and/or surgery]), and neurocognitive impairment. Latent class analysis with 5 indicators (employment, independent living, assistance with routine and/or personal care needs, driver’s license, marital or partner status) identified classes of functional independence. Path analysis tested associations among treatment exposures, neurocognitive impairment, chronic health conditions, and functional independence. Statistical tests were 2-sided.

Results
Cranial radiation exposure decreased over time (51%, 1970s; 46%, 1980s; 27%, 1990s]. However, compared with siblings, survivors with any treatment exposure were at elevated risk for neurocognitive impairment, including surgery only (eg, memory: relative risk = 2.22; task efficiency: relative risk = 1.88; both P &lt; .001). Three classes of functional independence were identified: independent (58%), moderately independent (20%), and nonindependent (22%). Cranial radiation was associated with nonindependence through impaired task efficiency (β = 0.06), sensorimotor (β = 0.06), and endocrine (β = 0.10) chronic health conditions and through the associations between these conditions and task efficiency (each β = 0.04). Sensorimotor and endocrine chronic health conditions were associated with nonindependence through memory.

Conclusion
Most long-term glioma survivors achieve adult independence. However, functional nonindependence is associated with treatment-related neurocognitive impairment and chronic health conditions.
Deciphering the protein ubiquitylation system in plants
Authors: Hua Zhihua 
Published: September 2023

Abstract
Protein ubiquitylation is a post-translational modification (PTM) process that covalently modifies a protein substrate with either mono-ubiquitin moieties or poly-ubiquitin chains often at the lysine residues. In Arabidopsis, bioinformatic predictions have suggested that over 5% of its proteome constitutes the protein ubiquitylation system. Despite advancements in functional genomic studies in plants, only a small fraction of this bioinformatically predicted system has been functionally characterized. To expand our understanding about the regulatory function of protein ubiquitylation to that rivalling several other major systems, such as transcription regulation and epigenetics, I describe the status, issues, and new approaches of protein ubiquitylation studies in plant biology. I summarize the methods utilized in defining the ubiquitylation machinery by bioinformatics, identifying ubiquitylation substrates by proteomics, and characterizing the ubiquitin E3 ligase-substrate pathways by functional genomics. Based on the functional and evolutionary analyses of the F-box gene superfamily, I propose a deleterious duplication model for the large expansion of this family in plant genomes. Given this model, I present new perspectives of future functional genomic studies on the plant ubiquitylation system to focus on core and active groups of ubiquitin E3 ligase genes.
Proteomic biomarker evaluation using antibody microarrays: association between analytical methods such as microarray and ELISA
Authors: Gumanova Nadezhda G , Bogdanova Natalya L , Metelskaya Victoria A 
Published: September 2023

Abstract

Objective
To evaluate the associations between analytical methods, such as microarray and enzyme-linked immunosorbent assay (ELISA); expedient cutoffs; and the lowest possible number of microarrays in analysis for target biomarker estimation in case-control studies.

Methods
This study included 321 serum specimens, gathered in different case-control studies to test for atherosclerosis and atrial fibrillation. Among them, 48 serum specimens were analyzed using microarray technology. We used ELISA and commercial kits for confirmation of the results.

Results
Three proteins—cadherin-P, neuronal nitric oxide synthase, and adenovirus fiber—were shown to have distinctly different values in the case group vs the control group. As a result, we used those proteins as the target for confirmation using our alternative analytical method. Also, these protein values represented the limiting range between the highest and lowest differences in case-control groups. The results of microarray assay were confirmed using ELISA and commercial kits in the same specimens, in which microarray profiling was performed, and also in separate large case-control groups.

Conclusions
A 1.5-fold difference in the protein content, as measured using microarray technology, was shown to be sufficient for further investigation of the candidate proteins. As few as 3 microarrays were considered sufficient for perspective evaluation of the target proteins. Microarray serum profiling, therefore, provides semiquantitative determination of protein in serum.
Optimizing an exercise training program in pediatric brain tumour survivors: Does timing postradiotherapy matter?
Authors: Baudou Éloïse , Ryan Jennifer L , Cox Elizabeth , Nham Lisa , Johnston Krista , Bouffet Éric , Bartels Ute , Timmons Brian , de Medeiros Cynthia , Mabbott Donald J 
Published: September 2023

Abstract

Background
While exercise training (ET) programs show positive outcomes in cognition, motor function, and physical fitness in pediatric brain tumor (PBT) survivors, little is known about the optimal timing of intervention. The aim of this work was to explore the feasibility and benefits of ET based on its timing after radiotherapy.

Methods
This retrospective analysis (ClinicalTrials.gov, NCT01944761) analyzed data based on the timing of PBT survivors' participation in an ET program relative to their completion of radiotherapy: &lt;2 years (n = 9), 2–5 years (n = 10), and &gt; 5 years (n = 13). We used repeated measures analysis of variance to compare feasibility and efficacy indicators among groups, as well as correlation analysis between ET program timing postradiotherapy and preliminary treatment effects on cognition, motor function and physical fitness outcomes.

Results
Two to five years postradiotherapy was the optimal time period in terms of adherence (88.5%), retention (100%), and satisfaction (more fun, more enjoyable and recommend it more to other children). However, the benefits of ET program on memory recognition (r = −0.379, P = .047) and accuracy (r = −0.430, P = .032) decreased with increased time postradiotherapy. Motor function improved in all groups, with greater improvements in bilateral coordination (P = .043) earlier postradiotherapy, and in running (P = .043) later postradiotherapy. The greatest improvement in pro-rated work rate occurred in the &lt; 2-year group (P = .008).

Conclusion
Participation in an ET program should be offered as part of routine postradiotherapy care in the first 1–2 years and strongly encouraged in the first 5 years.
The Impact of Infectious Disease Syndromes on Activities During Military Travel
Authors: Boatwright Michael A , Kuo Huai-Ching , Lindholm David A , Griffith Tara , Colombo Rhonda E , Tribble David R , O’Connell Robert , Lalani Tahaniyat 
Published: September 2023

Abstract

Background
We evaluated the impact of infectious disease (ID) syndromes on US active duty (AD) servicemembers returning from overseas deployment (DEP), military training exercises (EXR), or short-term military travel (eg, temporary assignment of duty [TDY]).

Methods
We conducted a survey-based assessment of US AD servicemembers returning from DEP, EXR, or TDY between 2015 and 2019. Subjects completed a post-travel survey capturing symptoms of travelers’ diarrhea (TD), influenza-like illness (ILI), and febrile illness (FI). Risk factors associated with any ID syndrome (ie, either TD, ILI, or FI) that impacted daily activities were assessed using a logistic regression model with backward selection.

Results
One-third of servicemembers (654/1822) experienced an ID syndrome, and 26% (471/1822) reported a ≥50% reduction in activity level due to an ID syndrome (median duration, 3 days). TD was the most common ID syndrome experienced and accounted for 73% (346/471) of ID syndromes impacting daily activities. The greatest impact of ID syndromes was observed in servicemembers on DEP. Compared with servicemembers on EXR or TDY, those on DEP had a longer duration of travel and a delayed period of risk for ID syndromes. Multivariate analysis identified high-risk exposures (ie, environmental exposures, close contact with locals, consuming food from street vendors) and behaviors (ie, inability to sanitize hands before meals) that could be used to inform mitigation strategies.

Conclusions
ID syndromes result in a significant loss of productivity during military travel. Addressing modifiable risk factors and access to TD self-treatment in high-risk settings may help mitigate the impact of ID threats during military travel.
Predator exclosures increase nest success but reduce adult survival and increase dispersal distance of Piping Plovers, indicating exclosures should be used with caution
Authors: Stantial Michelle L , Cohen Jonathan B , Darrah Abigail J , Maslo Brooke 
Published: September 2023

Abstract
Diagnosing unsuccessful population outcomes for endangered species requires understanding relationships among vital rates, ecological conditions, and management variables, including unintended consequences of management actions. The federally threatened Piping Plover (Charadrius melodus) has remained below recovery goals, despite intensive management, including the use of nest exclosures to protect eggs from predation. We studied ecological factors and management actions affecting nest success, survival, site fidelity, and dispersal of the New Jersey, USA population of Piping Plovers over a 7-yr period, focused on evaluating the impact of exclosures on demography. While exclosures increased nest success by 62% over a 34-day period, exclosed nests were 4.7 times more likely to be abandoned, which was likely a consequence of adult mortality. Abandoned nests were associated with lower adult survival, particularly for males, but there was evidence that site fidelity was greater for birds whose last nest was exclosed vs. unexclosed. Regardless of exclosure status, females who abandoned their first nesting attempt dispersed 10 times farther between attempts than those whose first nest attempts were lost to other causes. Moreover, females that abandoned their last nesting attempts dispersed farther than females that lost their last nest to predation or flooding. This difference was more substantial for males. Our results corroborate studies documenting adverse impacts of exclosures on survival, and, for the first time, demonstrate that surviving mates (particularly females) emigrate from the breeding site, resulting in a realized loss of a local breeding pair. Further, we used an online population project model (i.e., PiperEx) to demonstrate that exclosures are not expected to improve growth rates in New Jersey. We conclude that there is a trade-off among increased nest survival, reduced adult survival and increased emigration rates, and we encourage managers to consider whether exclosures are worth the protection of eggs from predators using online decision support tools.
Integrative analysis reveals the recurrent genetic etiologies in idiopathic pulmonary fibrosis
Authors: Guo S , Dong Y , Wang C , Jiang Y , Xiang R , Fan L -L , Luo H , Liu L 
Published: September 2023

SummaryBackgroundIdiopathic pulmonary fibrosis (IPF) is increasingly recognized as a chronic, progressive and fatal lung disease with an unknown etiology. Current studies focus on revealing the genetic factors in the risk of IPF, making the integrative analysis of genetic variations and transcriptomic alterations of substantial value.AimThis study aimed to improve the understanding of the molecular basis of IPF through an integrative analysis of whole-exome sequencing (WES), bulk RNA sequencing (RNA-seq) and single-cell RNA sequencing (scRNA-seq) data.MethodsWES is a powerful tool for studying the genetic basis of IPF, allowing for the identification of genetic variants that may be associated with the development of the disease. RNA-seq data provide a comprehensive view of the transcriptional changes in IPF patients, while scRNA-seq data offer a more granule view of cell-type-specific alterations.ResultsIn this study, we identified a comprehensive mutational landscape of recurrent genomic and transcriptomic variations, including single-nucleotide polymorphisms, CNVs and differentially expressed genes, in IPF populations, which may play a significant role in the development and progression of IPF.ConclusionsOur study provided valuable insights into the genetic and transcriptomic variations associated with IPF, revealing changes in gene expression that may contribute to disease development and progression. These findings highlight the importance of an integrative approach to understanding the molecular mechanisms underlying IPF and may pave the way for identifying potential therapeutic targets.
Hand joints without radiographic osteoarthritis maintain their joint space width over 4 years despite what’s happening elsewhere in the hand
Authors: Driban Jeffrey B , Vo Nhung , Duryea Jeff , Schaefer Lena F , Haugen Ida K , Eaton Charles B , Roberts Mary B , Lu Bing , McAlindon Timothy 
Published: September 2023

Abstract

Objectives
We aimed to determine whether hand OA is characterized by systemic cartilage loss by assessing if radiographically normal joints had greater joint space width (JSW) loss over 4 years in hands with incident or prevalent OA elsewhere in the hand compared with hands without OA.

Methods
We used semi-automated software to measure JSW in the distal and proximal IP joints of 3368 participants in the Osteoarthritis Initiative who had baseline and 48-month hand radiographs. A reader scored 16 hand joints (including the thumb base) for Kellgren–Lawrence (KL) grade. A joint had OA if scored as KL ≥2. We identified three groups based on longitudinal hand OA status: no hand OA (KL &lt;2 in all 16 joints) at the baseline and 48-month visits, incident hand OA (KL &lt;2 in all 16 joints at baseline and then one or more joints with KL ≥2 at 48 months) and prevalent hand OA (one or more joints with KL ≥2 at baseline and 48 months). We then assessed if JSW in radiographically normal joints (KL 0) differed across these three groups. We calculated unpooled effect sizes to help interpret the differences between groups.

Results
We observed small differences in JSW loss that are unlikely to be clinically important in radiographically normal joints between those without hand OA (n = 1054) and those with incident (n = 102) or prevalent hand OA (n = 2212) (effect size range −0.01–0.24). These findings were robust when examining JSW loss dichotomized based on meaningful change and in other secondary analyses.

Conclusions
Hand OA is not a systemic disease of cartilage.
The impact of the Digital Content Directive on online platforms’ Terms of Service
Authors: Wiśniewska Katarzyna , Pałka Przemysław 
Published: September 2023

Abstract
The Digital Content Directive 2019/770 (the DCD), aiming to foster the Digital Single Market and improve consumer protection, became applicable on 1 January 2022. This article presents the results of the study of 100 Terms of Service (ToS) of online platforms, conducted to evaluate the Directive’s impact. By combining black letter analysis with qualitative and quantitative empirical research, the contribution sheds new light on the Directive’s assumptions, critically assesses its logic, and makes regulatory suggestions for European lawmakers. Our central finding is that a significant number of the studied contracts (28 per cent) do not contain descriptions of the digital content offered. Many of those that do, keep the descriptions extremely vague. Hence, the central institution of the Directive—conformity with the contract—might be less valuable than the lawmakers have assumed. Even though the DCD introduces the concept of ‘objective’ conformity, we show how, in the digital environment, it might lower legal certainty, defeating one of the purposes of the Directive. Moreover, we also demonstrate how the analysed ToS often fail to meet other requirements, such as the right to retrieve one’s content or the protection from unilateral content deletion. This begs the question about the regulatory approach, the efficacy of the chosen enforcement scheme and, more generally, the enforcement schemes used throughout the EU’s private law. To remedy these problems, we suggest engaging in more empirical research when designing future measures to protect consumers online and considering supplementing the existing enforcement schemes with administrative oversight like the one in the Digital Services Act.
Transcriptome and secretome profiling of sensory neurons reveals sex differences in pathways relevant to insulin sensing and insulin secretion
Authors: Moon Sohyun , Alsarkhi Lamyaa , Lin Tai‐Tu , Inoue Ryota , Tahiri Azeddine , Colson Cecilia , Cai Weikang , Shirakawa Jun , Qian Wei‐Jun , Zhao Jerry Yingtao , El Ouaamari Abdelfattah 
Published: September 2023

AbstractSensory neurons in the dorsal root ganglia (DRG) convey somatosensory and metabolic cues to the central nervous system and release substances from stimulated terminal endings in peripheral organs. Sex‐biased variations driven by the sex chromosome complement (XX and XY) have been implicated in the sensory–islet crosstalk. However, the molecular underpinnings of these male–female differences are not known. Here, we aim to characterize the molecular repertoire and the secretome profile of the lower thoracic spinal sensory neurons and to identify molecules with sex‐biased insulin sensing‐ and/or insulin secretion‐modulating activity that are encoded independently of circulating gonadal sex hormones. We used transcriptomics and proteomics to uncover differentially expressed genes and secreted molecules in lower thoracic T5‐12 DRG sensory neurons derived from sexually immature 3‐week‐old male and female C57BL/6J mice. Comparative transcriptome and proteome analyses revealed differential gene expression and protein secretion in DRG neurons in males and females. The transcriptome analysis identified, among others, higher insulin signaling/sensing capabilities in female DRG neurons; secretome screening uncovered several sex‐specific candidate molecules with potential regulatory functions in pancreatic β cells. Together, these data suggest a putative role of sensory interoception of insulin in the DRG–islet crosstalk with implications in sensory feedback loops in the regulation of β‐cell activity in a sex‐biased manner. Finally, we provide a valuable resource of molecular and secretory targets that can be leveraged for understanding insulin interoception and insulin secretion and inform the development of novel studies/approaches to fathom the role of the sensory–islet axis in the regulation of energy balance in males and females.
Dual Plate Fixation of Periprosthetic Distal Femur Fractures
Authors: Andring Nicholas A , Kaupp Shannon M , Henry Kaitlin A , Helmig Kathryn C , Sharon Babcock , Halvorson Jason J , Pilson Holly T , Carroll Eben A 
Published: September 2023

Abstract

Objectives:
Dual implants for distal femur periprosthetic fractures (DFPF) is a growing area of interest for these challenging fractures with dual plating (DP) emerging as a viable construct for these injuries. In the current study we review our experience with DP constructs.

Design:
Retrospective case series with comparison group

Setting:
Level 1 academic trauma center
Patients/Participants: Adults >50 years old sustaining comminuted OTA/AO 33-A2 or 33-A3 DFPF treated with either DP or a single distal femur locking plating (DFLP). Patients with simple 33-A1 fractures were excluded. Prior to 2018 patients underwent DFLP after which the treatment of choice at our institution became DP. 34 patients treated with DFLP and 38 with DP met inclusion and follow up criteria. The average patient age in the DFLP group was 74.8 +/- 7.3 years compared to 75.9 +/- 11.3 years in the DP group.

Intervention:
Dual plating or single DFLP

Main Outcome Measurements:
Reoperation rate, alignment, and complications

Results:
Average follow up was 18.2 +/- 13.8 months in the DFLP group and 19.8 +/- 16.1 months in the DP group (p=0.339). There were no statistical differences in demographics, fracture morphology, loss of reduction, or reoperation for any cause (p>.05). However, DP patients were more likely to be weight bearing in the twelve-week postoperative period (p <0.001) and return to their baseline ambulatory status (p = 0.004) compared to DFLP patients.

Conclusions:
Dual plating of distal femoral periprosthetic fractures maintained coronal alignment with a low reoperation rate even with immediate weight bearing and these patients regained baseline level of ambulation more reliably as compared to patients treated with a single distal femoral locking plate.