bluuebunny/crossref_metadata_2025_split huggingface dataset:
Methylphenidate differentially alters corticostriatal connectivity after traumatic brain injury
Authors: Mallas Emma-Jane , De Simoni Sara , Jenkins Peter O , David Michael C B , Bourke Niall J , Sharp David J 
Published: October 2024

Abstract
Traumatic brain injury commonly impairs attention and executive function and disrupts the large-scale brain networks that support these cognitive functions. Abnormalities of functional connectivity are seen in corticostriatal networks, which are associated with executive dysfunction and damage to neuromodulatory catecholaminergic systems caused by head injury. Methylphenidate, a stimulant medication that increases extracellular dopamine and noradrenaline, can improve cognitive function following traumatic brain injury. In this experimental medicine add-on study to a randomized, double-blind, placebo-controlled clinical trial, we test whether administration of methylphenidate alters corticostriatal network function and influences drug response.
Forty-three moderate–severe traumatic brain injury patients received 0.3 mg/kg of methylphenidate or placebo twice a day in 2-week blocks. Twenty-eight patients were included in the neuropsychological and functional imaging analysis (four females, mean age 40.9 ± 12.7 years, range 20–65 years) and underwent functional MRI and neuropsychological assessment after each block. 123I-Ioflupane single-photon emission computed tomography dopamine transporter scans were performed, and specific binding ratios were extracted from caudate subdivisions. Functional connectivity and the relationship to cognition were compared between drug and placebo conditions.
Methylphenidate increased caudate to anterior cingulate cortex functional connectivity compared with placebo and decreased connectivity from the caudate to the default mode network. Connectivity within the default mode network was also decreased by methylphenidate administration, and there was a significant relationship between caudate functional connectivity and dopamine transporter binding during methylphenidate administration. Methylphenidate significantly improved executive function in traumatic brain injury patients, and this was associated with alterations in the relationship between executive function and right anterior caudate functional connectivity. Functional connectivity is strengthened to brain regions, including the anterior cingulate, that are activated when attention is focused externally. These results show that methylphenidate alters caudate interactions with cortical brain networks involved in executive control. In contrast, caudate functional connectivity reduces to default mode network regions involved in internally focused attention and that deactivate during tasks that require externally focused attention. These results suggest that the beneficial cognitive effects of methylphenidate might be mediated through its impact on the caudate.
Methylphenidate differentially influences how the caudate interacts with large-scale functional brain networks that exhibit co-ordinated but distinct patterns of activity required for attentionally demanding tasks.
Suture-anchored cutaneous tension induces persistent hypertrophic scarring in a novel murine model
Authors: Li Yashu , Liu Anqi , Wang Jingyan , Yang Changsheng , Lv Kaiyang , He Weifeng , Wu Jun , Chen Wenbin 
Published: October 2024

Abstract

Background
Hypertrophic scars cause impaired skin appearance and function, seriously affecting physical and mental health. Due to medical ethics and clinical accessibility, the collection of human scar specimens is frequently restricted, and the establishment of scar experimental animal models for scientific research is urgently needed. The four most commonly used animal models of hypertrophic scars have the following drawbacks: the rabbit ear model takes a long time to construct; the immunodeficient mouse hypertrophic scar model necessitates careful feeding and experimental operations; female Duroc pigs are expensive to purchase and maintain, and their large size makes it difficult to produce a significant number of models; and mouse scar models that rely on tension require special skin stretch devices, which are often damaged and shed, resulting in unstable model establishment. Our group overcame the shortcomings of previous scar animal models and created a new mouse model of hypertrophic scarring induced by suture anchoring at the wound edge.

Methods
We utilized suture anchoring of incisional wounds to impose directional tension throughout the healing process, restrain wound contraction, and generate granulation tissue, thus inducing scar formation. Dorsal paired incisions were generated in mice, with wound edges on the upper back sutured to the rib cage and the wound edges on the lower back relaxed as a control. Macroscopic manifestation, microscopic histological analysis, mRNA sequencing, bioinformatics, and in vitro cell assays were also conducted to verify the reliability of this method.

Results
Compared with those in relaxed controls, the fibrotic changes in stretched wounds were more profound. Histologically, the stretched scars were hypercellular, hypervascular, and hyperproliferative with disorganized extracellular matrix deposition, and displayed molecular hallmarks of hypertrophic fibrosis. In addition, the stretched scars exhibited transcriptional overlap with mechanically stretched scars, and human hypertrophic and keloid scars. Phosphatidylinositol 3-kinase-serine/threonine-protein kinase B signaling was implicated as a profibrotic mediator of apoptosis resistance under suture-induced tension.

Conclusions
This straightforward murine model successfully induces cardinal molecular and histological features of pathological hypertrophic scarring through localized suture tension to inhibit wound contraction. The model enables us to interrogate the mechanisms of tension-induced fibrosis and evaluate anti-scarring therapies.
Linezolid Pharmacokinetic-Anemia Modeling in Children With Rifampicin-Resistant Tuberculosis
Authors: Brooks Jordan T , Solans Belén P , Béranger Agathe , Schaaf H Simon , van der Laan Louvina , Sharma Sangeeta , Furin Jennifer , Draper Heather R , Hesseling Anneke C , Garcia-Prats Anthony J , Savic Radojka M 
Published: October 2024

Abstract

Background
Linezolid, a component of rifampicin-resistant/multidrug-resistant tuberculosis (RR/MDR-TB) treatment, is associated with treatment-limiting toxicities, including anemia. Patient-level and linezolid pharmacokinetic risk factors for anemia have not been well described in children treated for RR/MDR-TB.

Methods
We evaluated the pharmacokinetics of linezolid and longitudinal hemoglobin data to validate an existing population linezolid pharmacokinetic model. We assessed the impact of linezolid pharmacokinetics and the risk of developing anemia in a prospectively enrolled cohort of children. A previously published population pharmacokinetic linezolid model was validated using nonlinear mixed effects modeling. A multivariable ordinal logistic regression model was built to predict the incidence of anemia.

Results
A total of 112 children, median age 7.2 years (interquartile range, 2.2–16.3), were included from South Africa (n = 87) and India (n = 25). Of these, 24 children contributed new linezolid pharmacokinetic data. The population pharmacokinetic model, which informs the currently recommended linezolid dosing in children (10–15 mg/kg), was validated with these additional new data. For every 1 g/dL lower baseline hemoglobin level, the odds of developing grade 3 or 4 anemia increased by 2.64 (95% confidence interval [CI], 1.98–3.62). For every 1 mg/L × h higher linezolid area under the concentration-time curve, the odds of developing grade 3 or 4 anemia increased by 1.012 (95% CI, 1.007–1.017).

Conclusions
Taken together, these data confirm currently recommended linezolid doses for children. The risk of anemia in children should be carefully considered and monitored. Initiating linezolid in children with low baseline hemoglobin increases the probability of experiencing grade 3 or 4 anemia.
Current Legal Fictions in Public Law
Authors: Allison John W F 
Published: October 2024

Abstract
The use of legal fiction in public law has shown no sign of abating, as demonstrated in the enactment of the Safety of Rwanda (Asylum and Immigration) Act 2024. Accompanying questions or concerns are about the degree to which they are problematic, useful, or detrimental, what is to be done about them, and whether their prevalence is specific to British or English legal culture. This article examines what has been done, or what has happened, to deal or to cope with them, in orthodox constitutional legal doctrine and administrative law liability. After adopting a working definition of legal fiction and showing Dicey’s own preoccupation with the constitution’s legal forms and fiction, it does so through two case studies. Both involve basic orthodox constitutional legal doctrines—parliamentary sovereignty and the rule of law—with which Dicey has long been associated. The one case study is of Parliament’s sovereignty, limitless in law, and limited in actuality. The other case study is of legal fiction in relation to developments in public authority liability under equality before the law, particularly for omissions, or non-conferrals of benefit. Through these studies, this article will argue that the fortunes of legal fiction in the British or English legal context have been not simply of all-or-nothing rejection or retention. They have been, because of the unease accompanying the use of legal fiction, also of their domestication, in analytical distinctions, and refinement of judicial language in common law reasoning. The extraordinary legal forms have been made more ordinary or so to appear, showing them as domesticated to have been and to remain of current, ongoing and present, relevance.
Novel troponin fragmentation assay to discriminate between Takotsubo syndrome and acute myocardial infarction
Authors: Airaksinen Juhani K E , Tuominen Tuulia , Paana Tuomas , Hellman Tapio , Vasankari Tuija , Salonen Selma , Junes Helea , Linko-Parvinen Anna , Pallari Hanna-Mari , Strandberg Marjatta , Teppo Konsta , Jaakkola Samuli , Wittfooth Saara 
Published: October 2024

Abstract

Aims
Cardiac troponin levels are elevated in Takotsubo syndrome (TTS) with significant overlap to acute myocardial infarction (MI). Long and intact cardiac troponin T (cTnT) forms are typical for MI. This study sought to assess whether the fragmentation composition of cTnT release in TTS differs from MI.

Methods and results
The concentration of long molecular forms of cTnT (long cTnT) was measured with a novel upconversion luminescence immunoassay and total cTnT with a commercial high-sensitivity cTnT assay in 24 TTS patients and in 84 Type 1 MI patients. The ratio of long to total cTnT (troponin ratio) was determined as a measure of cTnT fragmentation. Troponin ratio was lower in TTS patients [0.13 (0.10–0.20) vs. 0.62 (0.29–0.96), P &lt; 0.001]. In the receiver operating characteristic curve analyses, troponin ratio showed a better predictive power than total cTnT in discriminating TTS and MI patients {area under the curve [AUC] 0.869 [95% confidence interval (CI) 0.789–0.948] vs. 0.766 [95% CI 0.677–0.855], P = 0.047}. When restricting the analysis to patients with total cTnT below 1200 ng/L (maximal value in TTS patients), the respective AUC values for total cTnT and troponin ratio were 0.599 (95% CI 0.465–0.732) and 0.816 (95% CI 0.712–0.921) (P = 0.003). At a cut-off point of 0.12, troponin ratio correctly identified 95% of MI patients and 50% of TTS patients.

Conclusion
In contrast to Type 1 MI, only a small fraction of circulating cTnT in TTS exists in intact or long molecular forms. This clear difference in troponin composition could be of diagnostic value when evaluating patients with cTnT elevations and suspicion of TTS.

Clinical trial registration
URL: https://www.clinicaltrials.gov; Unique identifier: NCT04465591
Remote workers’ life quality and stress during COVID-19: a systematic review
Authors: Elisabetta Carraro , Paola Rapisarda , Acquadro Maran Daniela , Filippetti Sofia , Marco Palella , Pellegrino Eliana , Ferrante Margherita , Giuseppe La Torre , Fiore Maria 
Published: October 2024

Abstract
COVID-19 pandemic led to the adoption of a different working approach: “The remote working.” Evidence about the association of remote working with stress outcomes and life quality is lacking. This systematic review provides an overview of the effects of COVID-19 pandemic on remote-workers’ stress and life quality. We conducted systematic literature searches in databases including Pubmed, Scopus and Web of science, from September 2020 to September 2023. Screening of titles, abstracts, and full texts were performed according to the Preferred Reporting Item for Systematic Review and Meta-analyses. The quality of the included studies was assessed using the Newcastle-Ottawa Scale. The review highlighted possible predictors (work-family conflict or a condition of social isolation) associated with improvement or worsening of quality of life and stress. The results highlighted the association between stress and family difficulties (β: −0.02, P-value &lt;0.05), isolation during the first (β: −0.22, P-value &lt;0.05) and second pandemic waves (β: −0.40, P-value &lt;0.05) or due to the advancing age of workers (β:0.19, P-value &lt;0.05) and (β: −0.05, P-value &lt;0.05), furthermore some job categories presented greater stress such as teachers (16.94 ± 5.46). Conversely, remote working positively affected life quality, enhancing factors such as creativity (Average Variance Extracted, AVE: 0.41, R2: 0.17) and self-efficacy (AVE: 0.60, R2: 0.36). Future research should focus more on the relationship between work and family and on interventions that counteract social isolation.
Promoting physical activity among cancer survivors through general practice: a realist review
Authors: Sugiarto Matthew Patrio , Jabbour Victoria , Uebel Kerry , Agaliotis Maria , Clifford Briana , Chin Melvin , Harris Mark , Caperchione Cristina M , Vuong Kylie 
Published: October 2024

Abstract

Background
Multiple studies have shown that physical activity improves cancer survivorship, by decreasing risk of second primary cancers and chronic conditions. However, cancer survivor physical activity levels remain low. General practice presents more opportunities for lifestyle interventions, such as increasing physical activity. We conducted a realist review of physical activity interventions relevant to general practice.

Methods
A total of 9728 studies were obtained from a systematic search of the CINAHL, Embase, PsycINFO, PubMed, and SPORTDiscus databases from the inception of the electronic database to 21 June 2024. We focussed on intervention studies that improved physical activity among cancer survivors and were relevant to general practice. Data extraction focussed on: what makes physical activity interventions effective for cancer survivors (what works) and what factors promote physical activity for cancer survivors (for whom it works).

Results
Thirty-seven studies were used to generate themes on the components of physical activity interventions that are likely to work and for whom; these studies facilitated goal setting, action planning, self-monitoring, social support, and shaping of knowledge; through delivering tailored motivational support, evoking a teachable moment, and promoting the use of self-monitoring tools. Interventions that were cost-effective and easily implementable improved sustainability, deployability, and uptake by cancer survivors. Cancer survivor psychological and physical factors, such as baseline motivational levels and post-treatment symptoms, influenced the uptake of physical activity interventions.

Conclusion
Our realist review has highlighted opportunities for general practices to promote physical activity among cancer survivors through collaborative goal setting, action planning, self-monitoring, social support, and shaping of knowledge.
LukProt: A Database of Eukaryotic Predicted Proteins Designed for Investigations of Animal Origins
Authors: Sobala Łukasz F 
Published: October 2024

Abstract
The origins and early evolution of animals are subjects with many outstanding questions. One problem faced by researchers trying to answer them is the absence of a comprehensive database with sequences from nonbilaterians. Publicly available data are plentiful but scattered and often not associated with proper metadata. A new database presented in this paper, LukProt, is an attempt at solving this issue. The database contains protein sequences obtained mostly from genomic, transcriptomic, and metagenomic studies and is an extension of EukProt (Richter DJ, Berney C, Strassert JFH, Poh Y-P, Herman EK, Muñoz-Gómez SA, Wideman JG, Burki F, de Vargas C. EukProt: a database of genome-scale predicted proteins across the diversity of eukaryotes. Peer Community J. 2022:2:e56. https://doi.org/10.24072/pcjournal.173). LukProt adopts the EukProt naming conventions and includes data from 216 additional animals. The database is associated with a taxonomic grouping (taxogroup) scheme suitable for studying early animal evolution. Minor updates to the database will contain species additions or metadata corrections, whereas major updates will synchronize LukProt to each new version of EukProt, and releases are permanently stored on Zenodo (https://doi.org/10.5281/zenodo.7089120). A BLAST server to search the database is available at: https://lukprot.hirszfeld.pl/. Users are invited to participate in maintaining and correcting LukProt. As it can be searched without downloading locally, the database aims to be a convenient resource not only for evolutionary biologists, but for the broader scientific community as well.
Neighborhood Stressors and Epigenetic Age Acceleration Among Older Americans
Authors: Choi Eun Young , Ailshire Jennifer A 
Published: October 2024

Abstract

Objectives
Exposure to stressful neighborhood environments is a well-established risk factor for health deterioration and premature death. However, the biological underpinnings are not fully understood. Epigenetic aging may function as a key molecular pathway to adverse health outcomes among residents of high-stress neighborhoods. This study examines the associations between neighborhood social stressors (socioeconomic deprivation, observed and perceived disorder, and low social cohesion) and epigenetic age (DunedinPACE and Principal component adjusted [PC] PCHorvath, PCHannum, PCPhenoAge, PCGrimAge). Further, we identify subpopulations most vulnerable to neighborhood stressors.

Methods
Respondent data are from the 2016 Health and Retirement Study (HRS) DNA methylation subsample. Neighborhood data come from respondent reports (2014/2016) and the census (2012–2016 ACS). The analytic sample included 3,146 adults ages 56 and older (mean age = 68.8), of whom 54.9% were women and 19.3% were non-White.

Results
In multilevel regression models adjusting for sociodemographic covariates, all neighborhood stressors were associated with faster DunedinPACE (B = 0.008 to 0.017). Neighborhood deprivation, perceived disorder, and low cohesion were associated with PCPhenoAge (B = 0.27 to 0.40) or PCGrimAge acceleration (B = 0.23). Health behaviors explained these associations to some degree. However, no significant associations were found with PCHorvath and PCHannum. In interaction analyses, adverse associations with deprivation, observed disorder, and low cohesion were more pronounced for women. No consistent interactions were found for race/ethnic and education groups.

Discussion
Our findings indicate that neighborhood stressors can accelerate epigenetic aging, with older women particularly vulnerable to their effects. These findings provide insights into the biological foundations of health disparities rooted in neighborhood environments.
Corticosteroid Use in Randomized Clinical Trials of Biologics and Small Molecules in Inflammatory Bowel Disease: A Systematic Review
Authors: da Silva Bruno César , Papasotiriou Sam , Hanauer Stephen B 
Published: October 2024

AbstractBackground and AimsThis systematic review aims to elucidate the use of corticosteroids in randomized clinical trials (RCTs) evaluating biologics and small molecules for inflammatory bowel disease (IBD). We analyzed corticosteroid use during both the induction and maintenance phases, highlighting areas needing standardization and improvement in clinical research.MethodsWe selected placebo-controlled phase 3 RCTs involving adults with moderate to severe IBD. These studies included detailed reports on corticosteroid use during induction and maintenance phases, with clinical remission and/or corticosteroid-free clinical remission (CSF-CR) as primary endpoints.ResultsInitially, 324 studies were identified and refined to 26 RCTs after screening. Analysis revealed variability in corticosteroid administration. Over time, corticosteroid use showed a decreasing trend (Spearman ρ = −0.42, P = .045). Studies allowing higher corticosteroid doses (up to 40 mg/day of prednisone or equivalent) reported a higher proportion of corticosteroid users (51.8%, range: 42.9%-61%) compared to those excluding patients on doses &gt;20 mg/day (37.5%, range: 31.6%-51.8%; P = .007) or &gt;30 mg/day (41.1%, range: 29.6%-53.7%; P = .023). Trials with mandatory tapering protocols showed a narrower gap between overall clinical remission and CSF-CR rates, with an average difference of 6% in the group without mandatory tapering and 1.2% in the group with forced tapering (T-test P = .038; Cohen’s d ≈ 1.1).ConclusionsThis review highlights the variability in corticosteroid use across RCTs and its impact on evaluating new IBD therapies. Standardizing tapering protocols and defining CSF-CR are essential for accurate outcomes.
Extracting social support and social isolation information from clinical psychiatry notes: comparing a rule-based natural language processing system and a large language model
Authors: Patra Braja Gopal , Lepow Lauren A , Kasi Reddy Jagadeesh Kumar Praneet , Vekaria Veer , Sharma Mohit Manoj , Adekkanattu Prakash , Fennessy Brian , Hynes Gavin , Landi Isotta , Sanchez-Ruiz Jorge A , Ryu Euijung , Biernacka Joanna M , Nadkarni Girish N , Talati Ardesheer , Weissman Myrna , Olfson Mark , Mann J John , Zhang Yiye , Charney Alexander W , Pathak Jyotishman 
Published: October 2024

Abstract

Objectives
Social support (SS) and social isolation (SI) are social determinants of health (SDOH) associated with psychiatric outcomes. In electronic health records (EHRs), individual-level SS/SI is typically documented in narrative clinical notes rather than as structured coded data. Natural language processing (NLP) algorithms can automate the otherwise labor-intensive process of extraction of such information.

Materials and Methods
Psychiatric encounter notes from Mount Sinai Health System (MSHS, n = 300) and Weill Cornell Medicine (WCM, n = 225) were annotated to create a gold-standard corpus. A rule-based system (RBS) involving lexicons and a large language model (LLM) using FLAN-T5-XL were developed to identify mentions of SS and SI and their subcategories (eg, social network, instrumental support, and loneliness).

Results
For extracting SS/SI, the RBS obtained higher macroaveraged F1-scores than the LLM at both MSHS (0.89 versus 0.65) and WCM (0.85 versus 0.82). For extracting the subcategories, the RBS also outperformed the LLM at both MSHS (0.90 versus 0.62) and WCM (0.82 versus 0.81).

Discussion and Conclusion
Unexpectedly, the RBS outperformed the LLMs across all metrics. An intensive review demonstrates that this finding is due to the divergent approach taken by the RBS and LLM. The RBS was designed and refined to follow the same specific rules as the gold-standard annotations. Conversely, the LLM was more inclusive with categorization and conformed to common English-language understanding. Both approaches offer advantages, although additional replication studies are warranted.