bluuebunny/crossref_metadata_2025_split huggingface dataset:
GC-MS Based Metabolomics Analysis to Evaluate Short-Term Effect of Tumor Removal on Patients with Early-Stage Breast Cancer
Authors: Beksac Kemal , Reçber Tuba , Çetin Bahadır , Alp Orkun , Kaynaroğlu Volkan , Kır Sedef , Nemutlu Emirhan 
Published: April 2022

Abstract
In this study, it was aimed to demonstrate the short-term effect of breast cancer surgery and tumor removal on the metabolomic profiles of patients with early-stage breast cancer. This cohort consisted of 18 early-stage breast carcinoma patients who had breast cancer surgery to remove tumor and surrounding tissues. The blood samples obtained preoperatively and 24 h after surgery were used in this investigation. Gas chromatography–mass spectrometry (GC–MS) based metabolomic analysis was performed to determine the metabolites. The GC–MS-based metabolomics profile enabled the identification of 162 metabolites in the plasma samples. Postoperatively, glyceric acid, phosphoric acid, O-phosphocolamine, 2-hydroxyethyliminodiacetic acid, N-acetyl-D-mannosamine, N-acetyl-5-hydroxytryptamine, methyl stearate, methyl oleate, iminodiacetic acid, glycerol 1-phosphate, β-glycerol phosphate and aspartic acid were found to be significantly increased (P &lt; 0.05 for all), whereas saccharic acid, leucrose, gluconic acid, citramalic acid and acetol were significantly decreased (P &lt; 0.05 for all). Breast cancer surgery and tumor removal has an impact on the metabolomic profiles of patients with early-stage breast cancer. These findings can be used for understanding the pathogenesis of breast cancer biology and screening the success of the surgery.
Scotland’s Last Blasphemy Trials: Popular Unbelief and its Opponents, 1819–1844
Authors: Loughlin Felicity 
Published: April 2022

Abstract
This article provides the first detailed historical analysis of Scotland’s last blasphemy trials (1819–1844). During this period, numerous booksellers and publishers were convicted for selling printed works that denied, ridiculed and vilified the scriptures and the Christian religion. Despite their significance as the last cases of their kind in Scottish history, these trials are almost entirely absent from the existing scholarship. The article positions them as a response to the unprecedented rise of popular unbelief in the Scottish religious landscape, a phenomenon that has itself been overlooked or dismissed by historians. In doing so, it demonstrates their significance in the campaign to extend religious toleration to unbelievers and identifies the early nineteenth century as an important transitional period, in which public attitudes towards the right of unbelievers to express openly their disavowal of Christianity underwent a significant transformation. As the article shows, debates over Scottish blasphemy legislation intersected with wider debates between Scottish Christians over the validity of an established church protected by law, and with contemporary campaigns from English unbelievers and their liberal supporters for the unfettered freedom of opinion. By 1844, conflicting attitudes over the desirability, utility and legitimacy of policing unbelief deepened divisions between different groups of Scottish Christians, while opening new areas of common ground between certain kinds of Christians and unbelievers.
Evolution of Complex Regulation for Cell-Cycle Control
Authors: von der Dunk Samuel H. A. , Snel Berend , Hogeweg Paulien 
Published: April 2022

Abstract
Many questions remain about the interplay between adaptive and neutral processes leading to genome expansion and the evolution of cellular complexity. Genome size appears to be tightly linked to the size of the regulatory repertoire of cells (van Nimwegen E. 2003. Scaling laws in the functional content of genomes. Trends Gen. 19(9):479–484). In the context of gene regulation, we here study the interplay between adaptive and nonadaptive forces on genome and regulatory network in a computational model of cell-cycle adaptation to different environments. Starting from the well-known Caulobacter crescentus network, we report on ten replicate in silico evolution experiments where cells evolve cell-cycle control by adapting to increasingly harsh spatial habitats.
We find adaptive expansion of the regulatory repertoire of cells. Having a large genome is inherently costly, but also allows for improved cell-cycle behavior. Replicates traverse different evolutionary trajectories leading to distinct eco-evolutionary strategies. In four replicates, cells evolve a generalist strategy to cope with a variety of nutrient levels; in two replicates, different specialist cells evolve for specific nutrient levels; in the remaining four replicates, an intermediate strategy evolves. These diverse evolutionary outcomes reveal the role of contingency in a system under strong selective forces.
This study shows that functionality of cells depends on the combination of regulatory network topology and genome organization. For example, the positions of dosage-sensitive genes are exploited to signal to the regulatory network when replication is completed, forming a de novo evolved cell cycle checkpoint. Our results underline the importance of the integration of multiple organizational levels to understand complex gene regulation and the evolution thereof.
Frailty and COVID-19 mRNA Vaccine Antibody Response in the COVID-19 Community Research Partnership
Authors: Semelka Charles T , DeWitt Michael E , Callahan Kathryn E , Herrington David M , Alexander-Miller Martha A , Yukich Joshua O , Munawar Iqra , McCurdy Lewis H , Gibbs Michael A , Weintraub William S , Sanders John W 
Published: April 2022

Abstract

Background
COVID-19 has disproportionately affected older adults. Frailty has been associated with impaired vaccine response in other vaccine types, but the impact of frailty on mRNA vaccine response is undefined.

Methods
Observational study of adults aged 55 and older from 1 U.S. health care system between January 22, 2021 and September 16, 2021 with self-reported Moderna or Pfizer COVID-19 mRNA vaccine and an electronic frailty index (eFI) score from their medical record (n = 1 677). Participants’ frailty status was compared with positive antibody detection (seroconversion) following full vaccination and subsequent loss of positive antibody detection (seroreversion) using logistic regression models.

Results
Of 1 677 older adults with median (interquartile range) age, 67 (62 and 72) years, and frailty status (nonfrail: 879 [52%], prefrail: 678 [40%], and frail: 120 [7.2%]), seroconversion was not detected in 23 (1.4%) over 60 days following full vaccination. Frail individuals were less likely to seroconvert than nonfrail individuals, adjusted odds ratio (OR) 3.75, 95% confidence interval (CI; 1.04, 13.5). Seroreversion was detected in 50/1 631 individuals (3.1%) over 6 months of median follow-up antibody testing. Frail individuals were more likely to serorevert than nonfrail individuals, adjusted OR 3.02, 95% CI (1.17, 7.33).

Conclusion
Overall antibody response to COVID-19 mRNA vaccination was high across age and frailty categories. While antibody detection is an incomplete descriptor of vaccine response, the high sensitivity of this antibody combined with health-system data reinforce our conclusions that frailty is an independent predictor of impaired antibody response to the COVID-19 mRNA vaccines. Frailty should be considered in vaccine studies and prevention strategies.
Trajectories of Loneliness Among Older Women and Men: Variation by Sexual Identity?
Authors: Lam Jack , Campbell Alice 
Published: April 2022

AbstractBackground and ObjectivesThe aim of this study is to contribute to the literature on variation in later-life outcomes by sexual identity. Drawing on the Iridescent Life Course framework, we examined differences in loneliness trajectories, and tested the roles of social connectedness and support, and socioeconomic and health statuses in explaining any observed disparities.Research Design and MethodsUsing growth models, we analyzed 19 years of data (2001–2019) from adults aged 50 years and older from the Household, Income and Labour Dynamics in Australia Survey (n = 5,500 individuals), where a question on sexual identity was asked twice in the study.ResultsOne percent of our sample reported a change in their sexual identity, which we grouped with individuals who reported as bisexual. Our sample comprised of 45.3% heterosexual men, 52.2% heterosexual women, 0.6% gay men, 0.6% lesbian women, 0.6% bisexual-plus men, and 0.6% bisexual-plus women. We found bisexual-plus men were vulnerable to loneliness as they aged. This group had the highest levels of loneliness at age 50, and differences compared with heterosexual men persisted over time. Loneliness of bisexual-plus men increased steeply from age 70. Socioeconomic and health statuses did not explain the increased loneliness of older bisexual-plus men. Lower social support and connectedness partly accounted for these disparities.Discussion and ImplicationsFindings are discussed with regards to existing research and theories on social disadvantage and resilience over the life course. We expand knowledge on factors explaining loneliness and how it varies in women and men by sexual identity.
Evaluations of effective coverage of maternal and child health services: A systematic review
Authors: Ferede Gebremedhin Aster , Dawson Angela , Hayen Andrew 
Published: April 2022

Abstract
Conventionally used coverage measures do not reflect the quality of care. Effective coverage (EC) assesses the extent to which health care services deliver potential health gains to the population by integrating concepts of utilization, need and quality. We aimed to conduct a systematic review of studies evaluating EC of maternal and child health services, quality measurement strategies and disparities across wealth quantiles. A systematic search was performed in six electronic databases [MEDLINE, EMBASE, Cumulative Index of Nursing and Allied Health (CINAHL), Scopus, Web of Science and Maternity and Infant Care] and grey literature. We also undertook a hand search of references. We developed search terms having no restrictions based on publication period, country or language. We included studies which reported EC estimates based on the World Health Organization framework of measuring EC. Twenty-seven studies, all from low- and middle-income settings (49 countries), met the criteria and were included in the narrative synthesis of the results. Maternal and child health intervention(s) and programme(s) were assessed either at an individual level or as an aggregated measure of health system performance or both. The EC ranged from 0% for post-partum care to 95% for breastfeeding. When crude coverage measures were adjusted to account for the quality of care, the EC values turned lower. The gap between crude coverage and EC was as high as 86%, and it signified a low quality of care. The assessment of the quality of care addressed structural, process and outcome domains individually or combined. The wealthiest 20% had higher EC of services than the poorest 20%, an inequitable distribution of coverage. More efforts are needed to improve the quality of maternal and child health services and to eliminate the disparities. Moreover, considering multiple dimensions of quality and the use of standard measurements are recommended to monitor coverage effectively.
Hippocampals neurogenesis is impaired in mice with a deletion in the coiled coil domain of Talpid3—implications for Joubert syndrome
Authors: Bashford Andrew L , Subramanian Vasanta 
Published: April 2022

AbstractMutations in Talpid3, a basal body protein essential for the assembly of primary cilia, have been reported to be causative for Joubert Syndrome (JS). Herein, we report prominent developmental defects in the hippocampus of a conditional knockout mouse lacking the conserved exons 11 and 12 of Talpid3. At early postnatal stages, the Talpid3 mutants exhibit a reduction in proliferation in the dentate gyrus and a disrupted glial scaffold. The occurrence of mis-localized progenitors in the granule cell layer suggests a role for the disrupted glial scaffold in cell migration resulting in defective subpial neurogenic zone-to-hilar transition. Neurospheres derived from the hippocampus of Talpid3fl/flUbcCre mouse, in which Talpid3 was conditionally deleted, lacked primary cilia and were smaller in size. In addition, neurosphere cells showed a disrupted actin cytoskeleton and defective migration. Our findings suggest a link between the hippocampal defects and the learning/memory deficits seen in JS patients.
Emulating a target trial of intensive nurse home visiting in the policy-relevant population using linked administrative data
Authors: Moreno-Betancur Margarita , Lynch John W , Pilkington Rhiannon M , Schuch Helena S , Gialamas Angela , Sawyer Michael G , Chittleborough Catherine R , Schurer Stefanie , Gurrin Lyle C 
Published: April 2022

Abstract

Background
Populations willing to participate in randomized trials may not correspond well to policy-relevant target populations. Evidence of effectiveness that is complementary to randomized trials may be obtained by combining the ‘target trial’ causal inference framework with whole-of-population linked administrative data.

Methods
We demonstrate this approach in an evaluation of the South Australian Family Home Visiting Program, a nurse home visiting programme targeting socially disadvantaged families. Using de-identified data from 2004–10 in the ethics-approved Better Evidence Better Outcomes Linked Data (BEBOLD) platform, we characterized the policy-relevant population and emulated a trial evaluating effects on child developmental vulnerability at 5 years (n = 4160) and academic achievement at 9 years (n = 6370). Linkage to seven health, welfare and education data sources allowed adjustment for 29 confounders using Targeted Maximum Likelihood Estimation (TMLE) with SuperLearner. Sensitivity analyses assessed robustness to analytical choices.

Results
We demonstrated how the target trial framework may be used with linked administrative data to generate evidence for an intervention as it is delivered in practice in the community in the policy-relevant target population, and considering effects on outcomes years down the track. The target trial lens also aided in understanding and limiting the increased measurement, confounding and selection bias risks arising with such data. Substantively, we did not find robust evidence of a meaningful beneficial intervention effect.

Conclusions
This approach could be a valuable avenue for generating high-quality, policy-relevant evidence that is complementary to trials, particularly when the target populations are multiply disadvantaged and less likely to participate in trials.
Herpes Simplex Virus-2 Variation Contributes to Neurovirulence During Neonatal Infection
Authors: Hayes Cooper K , Villota Christopher K , McEnany Fiona B , Cerón Stacey , Awasthi Sita , Szpara Moriah L , Friedman Harvey M , Leib David A , Longnecker Richard , Weitzman Matthew D , Akhtar Lisa N 
Published: April 2022

AbstractHerpes simplex virus (HSV) infection of the neonatal brain causes severe encephalitis and permanent neurologic deficits. However, infants infected with HSV at the time of birth follow varied clinical courses, with approximately half of infants experiencing only external infection of the skin rather than invasive neurologic disease. Understanding the cause of these divergent outcomes is essential to developing neuroprotective strategies. To directly assess the contribution of viral variation to neurovirulence, independent of human host factors, we evaluated clinical HSV isolates from neonates with different neurologic outcomes in neurologically relevant in vitro and in vivo models. We found that isolates taken from neonates with encephalitis are more neurovirulent in human neuronal culture and mouse models of HSV encephalitis, as compared to isolates collected from neonates with skin-limited disease. These findings suggest that inherent characteristics of the infecting HSV strain contribute to disease outcome following neonatal infection.
On the misuse of regressions of price on the HHI in merger review
Authors: Miller Nathan , Berry Steven , Scott Morton Fiona , Baker Jonathan , Bresnahan Timothy , Gaynor Martin , Gilbert Richard , Hay George , Jin Ginger , Kobayashi Bruce , Lafontaine Francine , Levinsohn James , Marx Leslie , Mayo John , Nevo Aviv , Pakes Ariel , Rose Nancy , Rubinfeld Daniel , Salop Steven , Schwartz Marius , Seim Katja , Shapiro Carl , Shelanski Howard , Sibley David , Sweeting Andrew , Wosinska Marta 
Published: April 2022

Abstract
The article explains why regressions of price on HHI should not be used in merger review. Both price and HHI are equilibrium outcomes determined by demand, supply, and the factors that drive them. Thus, a regression of price on the HHI does not recover a causal effect that could inform the likely competitive effects of a merger. Nonetheless, economic theory is consistent with the legal presumption that a merger is likely to have adverse competitive effects if it occurs in a concentrated market and makes that market more concentrated.
Growth and nitrogen status of cotton (Gossypium hirsutum L.) under salt stress revealed using 15N-labeled fertilizer
Authors: Heng Tong , He Xin-Lin , Yang Guang , Tian Li-Jun , Li Fa-Dong , Yang Li-Li , Zhao Li , Feng Yue , Xu Xuan 
Published: April 2022

Abstract
Salt stress is a vital factor limiting nitrogen uptake and cotton growth in arid regions. The mechanisms underlying salt stress tolerance in cotton plants under high soil salinity have not been fully elucidated. Therefore, the aim of this study was to examine the proportion and mechanism of cotton nitrogen uptake under salt stress using the 15N isotope labeling technique. Cotton plants were grown in four undisturbed saline soils (1, 3, 6 and 9 dS m−1), and the experiment was designed using the ENVIRO-GRO (E-G) model. The results showed that the dry matter of roots, stems and leaves of the cotton parts in slightly saline soil (C2, 3 dS m−1) was not significant compared with the non-saline soil (C1, 1 dS m−1). The cotton fruit grown in low-salinity soil (C2, 3 dS m−1) had significantly higher dry matter than that grown in the other treatments, implying that cotton plants grown in 3 dS m−1 soil have the best nitrogen uptake and salt tolerance. Cotton plants grown in weakly (C3, 6 dS m−1) and moderately (C4, 9 dS m−1) saline soils exhibited premature senescence. The distribution of total nitrogen and nitrate content in cotton was the best explanatory variable of total 15N recovery, of which cotton 15N recovery was between 26.1% and 47.2%, and soil 15N recovery was between 7.7% and 14.9%. Our findings provide guidance for further exploitation and utilization of saline soil resources and sustainable development of the agricultural soil ecosystem in arid regions.
Child Posttraumatic Stress after Parental Cancer: Associations with Individual and Family Factors
Authors: Egberts Marthe R , Verkaik Dineke , van Baar Anneloes L , Mooren Trudy T M , Spuij Mariken , de Paauw-Telman Liesbeth G E , Boelen Paul A 
Published: April 2022

Abstract

Objective
This study aimed to examine the severity of posttraumatic stress disorder (PTSD) symptoms in children of parents with cancer and to identify individual and family factors associated with these symptoms.

Methods
The sample consisted of 175 children (52% girls, aged M = 11.98, SD = 3.20, range = 6–20 years) from 92 families, of which 90 parents with a current or past cancer diagnosis and 71 healthy co-parents also completed questionnaires. Children reported on PTSD symptoms, trauma-related cognitions, emotion regulation difficulties, general family functioning, and family communication. Both parents reported on their own PTSD symptoms. Associations were investigated using multilevel regression.

Results
Twenty-seven percentage of the children showed clinically relevant PTSD symptoms. Intraclass correlations indicated that children from the same family showed little overlap in these symptoms. Multilevel analyses showed that child trauma-related cognitions and emotion regulation difficulties were related to higher levels of PTSD symptoms at the individual level. General family functioning was only related to child PTSD symptoms at the family level. Child PTSD severity was unrelated to parental PTSD symptoms and family communication at the family level when taking into account the other factors.

Conclusions
The current study highlights the psychological impact of parental cancer on children. Individual factors contributed more strongly to child PTSD symptoms than family factors. Trauma-related cognitions and emotion regulation difficulties might be targeted through specific psychoeducation for children and parents, family-oriented support and interventions, and evidence-based treatments for child PTSD.
SETDB1 fuels the lung cancer phenotype by modulating epigenome, 3D genome organization and chromatin mechanical properties
Authors: Zakharova Vlada V , Magnitov Mikhail D , Del Maestro Laurence , Ulianov Sergey V , Glentis Alexandros , Uyanik Burhan , Williart Alice , Karpukhina Anna , Demidov Oleg , Joliot Veronique , Vassetzky Yegor S , Mège René-Marc , Piel Matthieu , Razin Sergey V , Ait-Si-Ali Slimane 
Published: April 2022

Abstract
Imbalance in the finely orchestrated system of chromatin-modifying enzymes is a hallmark of many pathologies such as cancers, since causing the affection of the epigenome and transcriptional reprogramming. Here, we demonstrate that a loss-of-function mutation (LOF) of the major histone lysine methyltransferase SETDB1 possessing oncogenic activity in lung cancer cells leads to broad changes in the overall architecture and mechanical properties of the nucleus through genome-wide redistribution of heterochromatin, which perturbs chromatin spatial compartmentalization. Together with the enforced activation of the epithelial expression program, cytoskeleton remodeling, reduced proliferation rate and restricted cellular migration, this leads to the reversed oncogenic potential of lung adenocarcinoma cells. These results emphasize an essential role of chromatin architecture in the determination of oncogenic programs and illustrate a relationship between gene expression, epigenome, 3D genome and nuclear mechanics.
TADeus2: a web server facilitating the clinical diagnosis by pathogenicity assessment of structural variations disarranging 3D chromatin structure
Authors: Poszewiecka Barbara , Pienkowski Victor Murcia , Nowosad Karol , Robin Jérôme D , Gogolewski Krzysztof , Gambin Anna 
Published: April 2022

Abstract
In recent years great progress has been made in identification of structural variants (SV) in the human genome. However, the interpretation of SVs, especially located in non-coding DNA, remains challenging. One of the reasons stems in the lack of tools exclusively designed for clinical SVs evaluation acknowledging the 3D chromatin architecture. Therefore, we present TADeus2 a web server dedicated for a quick investigation of chromatin conformation changes, providing a visual framework for the interpretation of SVs affecting topologically associating domains (TADs). This tool provides a convenient visual inspection of SVs, both in a continuous genome view as well as from a rearrangement’s breakpoint perspective. Additionally, TADeus2 allows the user to assess the influence of analyzed SVs within flaking coding/non-coding regions based on the Hi-C matrix. Importantly, the SVs pathogenicity is quantified and ranked using TADA, ClassifyCNV tools and sampling-based P-value. TADeus2 is publicly available at https://tadeus2.mimuw.edu.pl.