bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacological and cell-based treatments to increase local skin flap viability in animal models
Authors: Berry Charlotte E. , Le Thalia , An Nicholas , Griffin Michelle , Januszyk Micheal , Kendig Carter B. , Fazilat Alexander Z. , Churukian Andrew A. , Pan Phoebe M. , Wan Derrick C. 
Published: January 2024

AbstractLocal skin flaps are frequently employed for wound closure to address surgical, traumatic, congenital, or oncologic defects. (1) Despite their clinical utility, skin flaps may fail due to inadequate perfusion, ischemia/reperfusion injury (IRI), excessive cell death, and associated inflammatory response. (2) All of these factors contribute to skin flap necrosis in 10–15% of cases and represent a significant surgical challenge. (3, 4) Once flap necrosis occurs, it may require additional surgeries to remove the entire flap or repair the damage and secondary treatments for infection and disfiguration, which can be costly and painful. (5) In addition to employing appropriate surgical techniques and identifying healthy, well-vascularized tissue to mitigate the occurrence of these complications, there is growing interest in exploring cell-based and pharmacologic augmentation options. (6) These agents typically focus on preventing thrombosis and increasing vasodilation and angiogenesis while reducing inflammation and oxidative stress. Agents that modulate cell death pathways such as apoptosis and autophagy have also been investigated. (7) Implementation of drugs and cell lines with potentially beneficial properties have been proposed through various delivery techniques including systemic treatment, direct wound bed or flap injection, and topical application. This review summarizes pharmacologic- and cell-based interventions to augment skin flap viability in animal models, and discusses both translatability challenges facing these therapies and future directions in the field of skin flap augmentation.
Arachidonic acid-derived lipid mediators in multiple sclerosis pathogenesis: fueling or dampening disease progression?
Authors: Broos Jelle Y. , van der Burgt Rianne T. M. , Konings Julia , Rijnsburger Merel , Werz Oliver , de Vries Helga E. , Giera Martin , Kooij Gijs 
Published: January 2024

Abstract
Background
Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system (CNS), characterized by neuroinflammation, demyelination, and neurodegeneration. Considering the increasing prevalence among young adults worldwide and the disabling phenotype of the disease, a deeper understanding of the complexity of the disease pathogenesis is needed to ultimately improve diagnosis and personalize treatment opportunities. Recent findings suggest that bioactive lipid mediators (LM) derived from ω-3/-6 polyunsaturated fatty acids (PUFA), also termed eicosanoids, may contribute to MS pathogenesis. For example, disturbances in LM profiles and especially those derived from the ω-6 PUFA arachidonic acid (AA) have been reported in people with MS (PwMS), where they may contribute to the chronicity of neuroinflammatory processes. Moreover, we have previously shown that certain AA-derived LMs also associated with neurodegenerative processes in PwMS, suggesting that AA-derived LMs are involved in more pathological events than solely neuroinflammation. Yet, to date, a comprehensive overview of the contribution of these LMs to MS-associated pathological processes remains elusive.

Main body
This review summarizes and critically evaluates the current body of literature on the eicosanoid biosynthetic pathway and its contribution to key pathological hallmarks of MS during different disease stages. Various parts of the eicosanoid pathway are highlighted, namely, the prostanoid, leukotriene, and hydroxyeicosatetraenoic acids (HETEs) biochemical routes that include specific enzymes of the cyclooxygenases (COXs) and lipoxygenases (LOX) families. In addition, cellular sources of LMs and their potential target cells based on receptor expression profiles will be discussed in the context of MS. Finally, we propose novel therapeutic approaches based on eicosanoid pathway and/or receptor modulation to ultimately target chronic neuroinflammation, demyelination and neurodegeneration in MS.

Short conclusion
The eicosanoid pathway is intrinsically linked to specific aspects of MS pathogenesis. Therefore, we propose that novel intervention strategies, with the aim of accurately modulating the eicosanoid pathway towards the biosynthesis of beneficial LMs, can potentially contribute to more patient- and MS subtype-specific treatment opportunities to combat MS.

Graphical Abstract
Planning and implementing community-based drug checking services in Scotland: a qualitative exploration using the consolidated framework for implementation research
Authors: Falzon Danilo , Carver Hannah , Masterton Wendy , Wallace Bruce , Sumnall Harry , Measham Fiona , Craik Vicki , Gittins Rosalind , Aston Elizabeth V. , Watson Kira , Hunter Carole , Priyadarshi Saket , Parkes Tessa 
Published: January 2024

Abstract
Background
Drug checking services (DCS) provide harm reduction support and advice to individuals based on chemical analysis of submitted substances of concern. Whilst there are currently no DCS in Scotland, community-based services are being planned in three cities.

Methods
In this paper, we report qualitative findings based on interviews with 43 participants, focused on perceptions of DCS and their implementation. Participants were relevant professionals, those with experience of drug use, and family members of those with experience of drug use. The Consolidated Framework for Implementation Research (CFIR) was used to inform data collection and analysis. We report findings under nine constructs/themes across the five CFIR domains.

Results
Participants noted the importance of DCS being implemented in low-threshold, trusted services with a harm reduction ethos, and outlined a range of further service design considerations such as speed of testing, and information provided through the analysis process. In relation to the ‘inner setting’, a key finding related to the potential value of leveraging existing resources in order to expand both reach and effectiveness of drug trend communication. The approach of local and national police to DCS, and the attitudes of the public and local community, were described as important external factors which could influence the success (or otherwise) of implementation. Bringing together a range of stakeholders in dialogue and developing tailored communication strategies were seen as ways to build support for DCS. Overall, we found high levels of support and perceived need for DCS amongst all stakeholder groups.

Conclusions
Our findings present initial implementation considerations for Scotland which could be further explored as DCS are operationalised. Further, our focus on implementation contexts is relevant to research on DCS more generally, given the minimal consideration of such issues in the literature.
Different modalities of patellar management in primary total knee arthroplasty: a Bayesian network meta-analysis of randomized controlled trials
Authors: Liu Lun , Li Juebei , Wang Yunlu , Li Xiyong , Han Pengfei , Li Xiaodong 
Published: January 2024

Abstract
Background
The primary management modalities for the patella in TKA include patellar resurfacing, patellar non-resurfacing, patellar resurfacing with denervation, and patellar non-resurfacing with denervation. Traditionally, meta-analyses have predominantly focused on examining comparisons between two management modalities. However, this study performed a network meta-analysis to compare all four patellar management interventions to identify the most optimal approach for patellar management in TKA.

Methods
A computer-based search of PubMed, China National Knowledge Infrastructure (CNKI), The Cochrane Library, Web of science, Embase, and MEDLINE databases was performed to identify randomized controlled trials focusing on the four management interventions for the patella in TKA. Comparisons included two-by-two comparisons as well as those involving more than two concurrent comparisons. The search timeframe spanned from inception to June 30, 2023. Two independent authors extracted the data and evaluated the quality of the literature. The Cochrane Collaboration Risk of Bias (ROB) tool was used to evaluate the overall quality of the literature. Subsequently, a network meta-analysis was conducted using the “gemtc” package of the R-4.2.3 software. Outcome measures such as anterior knee pain (AKP), reoperation rate, and patient satisfaction rate were evaluated using odd ratio (OR) and 95% confidence intervals (CI). Additionally, the knee society score (KSS), function score (FS), and range of motion (ROM) were evaluated using mean differences (MD) with associated 95% CI. The different treatment measures were ranked using the surfaces under the cumulative ranking curves (SUCRA).

Results
A total of 50 randomized controlled trials involving 9,283 patients were included in the analysis. The findings from this network meta-analysis revealed that patellar resurfacing exhibited significantly lower postoperative reoperation rate (OR 0.44, 95% CI 0.24–0.63) and AKP (OR 0.58, 95% CI 0.32–1) compared to non-resurfacing. Additionally, patellar resurfacing exhibited higher postoperative KSS clinical scores in comparison with non-resurfacing (MD: 1.13, 95% CI 0.18–2.11). However, for postoperative FS, ROM, and patient satisfaction, no significant differences were observed among the four management interventions.

Conclusion
Patellar resurfacing emerges as the optimal management modality in primary TKA. However, future studies should aim to reduce sources of heterogeneity and minimize the influence of confounding factors on outcomes.

Systematic review registration
https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023434418 identifier: CRD42023434418
An engineered ligand-responsive Csy4 endoribonuclease controls transgene expression from Sendai virus vectors
Authors: Kishimoto Takumi , Nishimura Ken , Morishita Kana , Fukuda Aya , Miyamae Yusaku , Kumagai Yutaro , Sumaru Kimio , Nakanishi Mahito , Hisatake Koji , Sano Masayuki 
Published: January 2024

Abstract
Background
Viral vectors are attractive gene delivery vehicles because of their broad tropism, high transduction efficiency, and durable expression. With no risk of integration into the host genome, the vectors developed from RNA viruses such as Sendai virus (SeV) are especially promising. However, RNA-based vectors have limited applicability because they lack a convenient method to control transgene expression by an external inducer.

Results
We engineered a Csy4 switch in Sendai virus-based vectors by combining Csy4 endoribonuclease with mutant FKBP12 (DD: destabilizing domain) that becomes stabilized when a small chemical Shield1 is supplied. In this Shield1-responsive Csy4 (SrC) switch, Shield1 increases Csy4 fused with DD (DD-Csy4), which then cleaves and downregulates the transgene mRNA containing the Csy4 recognition sequence (Csy4RS). Moreover, when Csy4RS is inserted in the viral L gene, the SrC switch suppresses replication and transcription of the SeV vector in infected cells in a Shield1-dependent manner, thus enabling complete elimination of the vector from the cells. By temporally controlling BRN4 expression, a BRN4-expressing SeV vector equipped with the SrC switch achieves efficient, stepwise differentiation of embryonic stem cells into neural stem cells, and then into astrocytes.

Conclusion
SeV-based vectors with the SrC switch should find wide applications in stem cell research, regenerative medicine, and gene therapy, especially when precise control of reprogramming factor expression is desirable.
Thyroid storm in pregnancy: a review
Authors: Vadini Vidhu , Vasistha Prabhav , Shalit Almog , Maraka Spyridoula 
Published: January 2024

Abstract
Background
Thyroid storm is a state of circulating thyroid hormone excess leading to multiorgan dysfunction and systemic decompensation. It typically occurs in the setting of poorly controlled hyperthyroidism and a precipitating illness or event. Management of thyroid storm in pregnancy poses unique diagnostic and therapeutic challenges.

Main body
Thyroid storm is a clinical diagnosis characterized by hyperpyrexia, tachyarrhythmias, congestive heart failure, gastrointestinal and neuropsychiatric disturbances. However, diagnostic scoring systems have not been validated in pregnancy.
Treatment involves specialist consultation, supportive care, and pharmacological options such as anti-thyroid medications, beta blockers, iodine solutions, glucocorticoids, and cholestyramine. These must be adapted and modified in pregnancy to prevent fetal and maternal complications.

Conclusion
There is a critical need to recognize thyroid storm during pregnancy and initiate proper medical interventions promptly.
Infant mortality in Italy: large geographic and ethnic inequalities
Authors: Simeoni Silvia , Frova Luisa , De Curtis Mario 
Published: January 2024

Abstract
Background
Neonatal and infant mortality rates are among the most significant indicators for assessing a country's healthcare and social development.
This study examined the trends in neonatal, post-neonatal, and infant mortality in Italy from 2016 to 2020 and analysed differences between children of Italian and foreign parents based on areas of residence, as well as the leading causes of death. Special attention was given to the analysis of mortality in 2020, the first year of the Covid-19 pandemic, and its comparison with previous years.

Methods
Data from 2016 to 2020 were collected by the Italian National Institute of Statistics and extracted from two national databases, the Causes of Death register and Live births registered in the population register. Neonatal, post-neonatal, and infant mortality rates were calculated using conventional definitions. The main analyses were conducted by comparing Italian citizens to foreigners and contrasting residents of the North with those of the South. Group comparisons were made using mortality rate ratios. The main causes of death were examined, and Poisson log-linear regression models were employed to investigate the relationships between mortality rate ratios for each cause of death and citizenship, place of residence and calendar year.

Results
In Italy, in 2020, the neonatal mortality rate was 1.76 deaths per thousand live births and it was 55% higher in foreign children than in Italian children. Foreign children had a higher mortality rate than Italians for almost all significant causes of death. Children born in the South of Italy, both Italian and foreign, had an infant mortality rate about 70% higher than residents in the North. Regions with higher infant mortality were Calabria, Sicily, Campania, and Apulia. In the South, mortality from neonatal respiratory distress and prematurity was higher.
In the first months of 2020, between March and June, the first Covid-19 wave, Italy experienced an increase in neonatal and infant mortality compared to the same period in 2016–2019, not directly related to SARS-CoV-19 infection. The primary cause was neonatal respiratory distress.

Conclusions
The neonatal and infant mortality rates indicate the persistence of profound inequalities in Italy between the North and the South and between Italian and foreign children.
The efficacy of a transdiagnostic sleep intervention for outpatients with sleep problems and depression, bipolar disorder, or attention deficit disorder: study protocol for a randomized controlled trial
Authors: Kragh Mette , Dyrberg Henny , Speed Maria , Pedersen Pernille , Kristiansen Sanne Toft , Martiny Klaus 
Published: January 2024

Abstract
Background
Patients with mental disorders have a higher prevalence of sleep problems than the general population. Sleep problems may include insomnia, circadian rhythm disorders, or hypersomnia. A transdiagnostic approach combining cognitive behavioral therapy for insomnia (CBT-I) with chronotherapy addressing a broad range of sleep problems has shown promising results in a limited number of studies. The aim of the study is to investigate the efficacy of a transdiagnostic sleep intervention for patients with sleep problems comorbid to bipolar disorder, unipolar depression, or attention deficit disorders. The primary hypothesis is that the intervention improves sleep quality compared with a control group. The secondary hypotheses are that the intervention increases subjective and objective sleep efficiency, reduces sleep onset latency, wake after sleep onset, number of awakenings, and severity of insomnia; and that it improves well-being, personal recovery, work ability, and consumption of sleep medication compared with a control group.

Methods
The study is a randomized controlled trial enrolling 88 outpatients with bipolar disorder, major depression, or attention deficit disorder with symptoms of various sleep problems (insomnia, circadian rhythm disorders, or hypersomnia). Patients are allocated to either an intervention group receiving six sessions of transdiagnostic sleep treatment or to a control group receiving a single session of sleep hygiene education. Assessments are made at baseline, at week two, and after 6 weeks in both groups. Actigraphy is performed continuously throughout the 6-week study period for all patients. The primary outcome is changes in the subjective appraisal of sleep quality (Pittsburgh Sleep Quality Index). The secondary outcomes are changes in sleep efficiency, sleep onset latency, wake after sleep onset, number of nocturnal awakenings (based on actigraph and sleep diary data), changes in insomnia severity (Insomnia Severity Index), well-being (WHO-5 Well-Being Index), personal recovery (INSPIRE-O), work ability (Work Ability Index), and consumption of sleep medication (sleep-diaries).

Discussion
The study was initiated in 2022 and the inclusion period will continue until mid-2024. The results may have implications for the development and implementation of additional treatment options for patients with mental disorders and comorbid sleep problems.

Trial registration
ClinicalTrials.gov. NCT05406414. Registered on June 6, 2022.
Gray matter covariations in autism: out-of-sample replication using the ENIGMA autism cohort
Authors: Mei Ting , Llera Alberto , Forde Natalie J. , van Rooij Daan , Floris Dorothea L. , Beckmann Christian F. , Buitelaar Jan K. 
Published: January 2024

Abstract
Background
Autism spectrum disorder (henceforth autism) is a complex neurodevelopmental condition associated with differences in gray matter (GM) volume covariations, as reported in our previous study of the Longitudinal European Autism Project (LEAP) data. To make progress on the identification of potential neural markers and to validate the robustness of our previous findings, we aimed to replicate our results using data from the Enhancing Neuroimaging Genetics Through Meta-Analysis (ENIGMA) autism working group.

Methods
We studied 781 autistic and 927 non-autistic individuals (6–30 years, IQ ≥ 50), across 37 sites. Voxel-based morphometry was used to quantify GM volume as before. Subsequently, we used spatial maps of the two autism-related independent components (ICs) previously identified in the LEAP sample as templates for regression analyses to separately estimate the ENIGMA-participant loadings to each of these two ICs. Between-group differences in participants’ loadings on each component were examined, and we additionally investigated the relation between participant loadings and autistic behaviors within the autism group.

Results
The two components of interest, previously identified in the LEAP dataset, showed significant between-group differences upon regressions into the ENIGMA cohort. The associated brain patterns were consistent with those found in the initial identification study. The first IC was primarily associated with increased volumes of bilateral insula, inferior frontal gyrus, orbitofrontal cortex, and caudate in the autism group relative to the control group (β = 0.129, p = 0.013). The second IC was related to increased volumes of the bilateral amygdala, hippocampus, and parahippocampal gyrus in the autism group relative to non-autistic individuals (β = 0.116, p = 0.024). However, when accounting for the site-by-group interaction effect, no significant main effect of the group can be identified (p > 0.590). We did not find significant univariate association between the brain measures and behavior in autism (p > 0.085).

Limitations
The distributions of age, IQ, and sex between LEAP and ENIGMA are statistically different from each other. Owing to limited access to the behavioral data of the autism group, we were unable to further our understanding of the neural basis of behavioral dimensions of the sample.

Conclusions
The current study is unable to fully replicate the autism-related brain patterns from LEAP in the ENIGMA cohort. The diverse group effects across ENIGMA sites demonstrate the challenges of generalizing the average findings of the GM covariation patterns to a large-scale cohort integrated retrospectively from multiple studies. Further analyses need to be conducted to gain additional insights into the generalizability of these two GM covariation patterns.
Exploring small non-coding RNAs as blood-based biomarkers to predict Alzheimer’s disease
Authors: Gutierrez-Tordera Laia , Papandreou Christopher , Novau-Ferré Nil , García-González Pablo , Rojas Melina , Marquié Marta , Chapado Luis A. , Papagiannopoulos Christos , Fernàndez-Castillo Noèlia , Valero Sergi , Folch Jaume , Ettcheto Miren , Camins Antoni , Boada Mercè , Ruiz Agustín , Bulló Mònica 
Published: January 2024

Abstract
Background
Alzheimer’s disease (AD) diagnosis relies on clinical symptoms complemented with biological biomarkers, the Amyloid Tau Neurodegeneration (ATN) framework. Small non-coding RNA (sncRNA) in the blood have emerged as potential predictors of AD. We identified sncRNA signatures specific to ATN and AD, and evaluated both their contribution to improving AD conversion prediction beyond ATN alone.

Methods
This nested case–control study was conducted within the ACE cohort and included MCI patients matched by sex. Patients free of type 2 diabetes underwent cerebrospinal fluid (CSF) and plasma collection and were followed-up for a median of 2.45-years. Plasma sncRNAs were profiled using small RNA-sequencing. Conditional logistic and Cox regression analyses with elastic net penalties were performed to identify sncRNA signatures for A+(T|N)+ and AD. Weighted scores were computed using cross-validation, and the association of these scores with AD risk was assessed using multivariable Cox regression models. Gene ontology (GO) and Kyoto encyclopaedia of genes and genomes (KEGG) enrichment analysis of the identified signatures were performed.

Results
The study sample consisted of 192 patients, including 96 A+(T|N)+ and 96 A-T-N- patients. We constructed a classification model based on a 6-miRNAs signature for ATN. The model could classify MCI patients into A-T-N- and A+(T|N)+ groups with an area under the curve of 0.7335 (95% CI, 0.7327 to 0.7342). However, the addition of the model to conventional risk factors did not improve the prediction of AD beyond the conventional model plus ATN status (C-statistic: 0.805 [95% CI, 0.758 to 0.852] compared to 0.829 [95% CI, 0.786, 0.872]). The AD-related 15-sncRNAs signature exhibited better predictive performance than the conventional model plus ATN status (C-statistic: 0.849 [95% CI, 0.808 to 0.890]). When ATN was included in this model, the prediction further improved to 0.875 (95% CI, 0.840 to 0.910). The miRNA-target interaction network and functional analysis, including GO and KEGG pathway enrichment analysis, suggested that the miRNAs in both signatures are involved in neuronal pathways associated with AD.

Conclusions
The AD-related sncRNA signature holds promise in predicting AD conversion, providing insights into early AD development and potential targets for prevention.