bluuebunny/crossref_metadata_2025_split huggingface dataset:
The anesthetic efficacy of ultrasound-guided lumbar plexus combined with quadratus lumborum block with Shamrock approach in total hip arthroplasty: study protocol for a randomized controlled trial
Authors: Wang Xiaofeng , Zhang Hui , Chen Yongzhu , Xie Zhenwei , Chen Moxi , Chen Yonglin , Zhang Junfeng 
Published: September 2023

Abstract
Introduction
The lumbar plexus originates from multiple segments of the spinal cord. Both single-level lumbar plexus block (LPB) and transmuscular quadratus lumborum block (TQLB) are commonly used to provide analgesia for the patients undergoing total hip arthroplasty (THA). However, neither of them can completely cover the lumbar plexus. Multiple-level LPB is also not recommended since this expert technique involves more potential risks. To achieve a better anesthetic effect and avoid risks, we propose to combine ultrasound-guided LPB with TQLB with Shamrock approach. We aim to assess the anesthetic efficacy of this combination technique and expect it will be an ideal alternative for conventional LPBs in THA.

Methods and analysis
In this prospective randomized controlled trial, 84 patients schedule for THA will be enrolled. The patients will be randomly assigned at a 1:1:1 ratio to receive LPB at L3 level (P group), T12 paravertebral block combined with LPB at L3 and L4 levels (TP group), or LPB combined with TQLB at L3 level (PQ group). Each method will be evaluated in terms of the successful rate of sensory blockade, postoperative pain, performance time of block, requirement for intraoperative sufentanil, cumulative doses of intraoperative vasoactive medications, and adverse events.

Ethics and dissemination
The study protocol has been approved by the institutional review board (IRB) at Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, China (No.2020–031). The results will be disseminated in a peer-reviewed journal and the ClinicalTrials.gov registry.

Trial registration
ClinicalTrials.gov, NCT04266236. Registered on 10 February 2020. ClinicalTrials.gov PRS: Record Summary NCT04266236.
Identification of novel genetic risk factors of dilated cardiomyopathy: from canine to human
Authors: Niskanen Julia E. , Ohlsson Åsa , Ljungvall Ingrid , Drögemüller Michaela , Ernst Robert F. , Dooijes Dennis , van Deutekom Hanneke W. M. , van Tintelen J. Peter , Snijders Blok Christian J. B. , van Vugt Marion , van Setten Jessica , Asselbergs Folkert W. , Petrič Aleksandra Domanjko , Salonen Milla , Hundi Sruthi , Hörtenhuber Matthias ,   DoGA consortium, Daub Carsten , Araujo César L. , Quintero Ileana B. , Kyöstilä Kaisa , Kaukonen Maria , Arumilli Meharji , Sarviaho Riika , Puurunen Jenni , Sulkama Sini , Karjalainen Sini , Sukura Antti , Syrjä Pernilla , Airas Niina , Pekkarinen Henna , Kareinen Ilona , Javela Hanna-Maaria , Knuuttila Anna , Nordgren Heli , Hagner Karoliina , Pääkkönen Tarja , Iivanainen Antti , Krjutskov Kaarel , Ezer Sini , Saarinen Auli , Katayama Shintaro , Yoshihara Masahito , Mukarram Abdul Kadir , Aljelaify Rasha Fahad , Ross Fiona , Raman Amitha , Stevens Irene , Gusev Oleg , Bannasch Danika , Schoenebeck Jeffrey J. , Kere Juha , Pyle W. Glen , Donner Jonas , Postma Alex V. , Leeb Tosso , Andersson Göran , Hytönen Marjo K. , Häggström Jens , Wiberg Maria , Friederich Jana , Eberhard Jenny , Harakalova Magdalena , van Steenbeek Frank G. , Wess Gerhard , Lohi Hannes 
Published: September 2023

Abstract
Background
Dilated cardiomyopathy (DCM) is a life-threatening heart disease and a common cause of heart failure due to systolic dysfunction and subsequent left or biventricular dilatation. A significant number of cases have a genetic etiology; however, as a complex disease, the exact genetic risk factors are largely unknown, and many patients remain without a molecular diagnosis.

Methods
We performed GWAS followed by whole-genome, transcriptome, and immunohistochemical analyses in a spontaneously occurring canine model of DCM. Canine gene discovery was followed up in three human DCM cohorts.

Results
Our results revealed two independent additive loci associated with the typical DCM phenotype comprising left ventricular systolic dysfunction and dilatation. We highlight two novel candidate genes, RNF207 and PRKAA2, known for their involvement in cardiac action potentials, energy homeostasis, and morphology. We further illustrate the distinct genetic etiologies underlying the typical DCM phenotype and ventricular premature contractions. Finally, we followed up on the canine discoveries in human DCM patients and discovered candidate variants in our two novel genes.

Conclusions
Collectively, our study yields insight into the molecular pathophysiology of DCM and provides a large animal model for preclinical studies.
Intra-articular delivery of an indoleamine 2,3-dioxygenase galectin-3 fusion protein for osteoarthritis treatment in male Lewis rats
Authors: Partain Brittany D. , Bracho-Sanchez Evelyn , Farhadi Shaheen A. , Yarmola Elena G. , Keselowsky Benjamin G. , Hudalla Gregory A. , Allen Kyle D. 
Published: September 2023

Abstract
Objective
Osteoarthritis (OA) is driven by low-grade inflammation, and controlling local inflammation may offer symptomatic relief. Here, we developed an indoleamine 2,3-dioxygenase and galectin-3 fusion protein (IDO-Gal3), where IDO increases the production of local anti-inflammatory metabolites and Gal3 binds carbohydrates to extend IDO’s joint residence time. In this study, we evaluated IDO-Gal3’s ability to alter OA-associated inflammation and pain-related behaviors in a rat model of established knee OA.

Methods
Joint residence was first evaluated with an analog Gal3 fusion protein (NanoLuc™ and Gal3, NL-Gal3) that produces luminescence from furimazine. OA was induced in male Lewis rats via a medial collateral ligament and medial meniscus transection (MCLT + MMT). At 8 weeks, NL or NL-Gal3 were injected intra-articularly (n = 8 per group), and bioluminescence was tracked for 4 weeks. Next, IDO-Gal3s’s ability to modulate OA pain and inflammation was assessed. Again, OA was induced via MCLT + MMT in male Lewis rats, with IDO-Gal3 or saline injected into OA-affected knees at 8 weeks post-surgery (n = 7 per group). Gait and tactile sensitivity were then assessed weekly. At 12 weeks, intra-articular levels of IL6, CCL2, and CTXII were assessed.

Results
The Gal3 fusion increased joint residence in OA and contralateral knees (p < 0.0001). In OA-affected animals, both saline and IDO-Gal3 improved tactile sensitivity (p = 0.008), but IDO-Gal3 also increased walking velocities (p ≤ 0.033) and improved vertical ground reaction forces (p ≤ 0.04). Finally, IDO-Gal3 decreased intra-articular IL6 levels within the OA-affected joint (p = 0.0025).

Conclusion
Intra-articular IDO-Gal3 delivery provided long-term modulation of joint inflammation and pain-related behaviors in rats with established OA.
Pan cancer characterization of genes whose expression has been associated with LINE-1 antisense promoter activity
Authors: Xu Baohong , Li Xueer , Zhang Shaoqi , Lian Meina , Huang Wenbin , Zhang Yin , Wang Yudong , Huang Zhiquan 
Published: September 2023

Abstract
Background
Long interspersed nuclear element-1 (LINE-1 or L1) comprises 17% of the human genome. As the only autonomous and active retrotransposons, L1 may take part in cancer initiation and progression in some ways. The studies of L1 in cancer mainly focus on the impact of L1 insertion into the new genome locus. The L1 5´ untranslated region (UTR) also contains antisense promoter (ASP) activity, generating L1-gene chimeric transcripts to a neighbor exon. Some of these ASP-associated genes have been reported to be overexpressed in cancer and promote cancer cell growth. However, little is known about overall expression patterns and the roles of L1 ASP-associated genes in human cancers.

Results
L1 ASP-associated genes were frequently dysregulated in cancer and associated with the cell cycle, the PI3K/AKT pathway, and the GTPase signaling pathway. The expression of L1 ASP-associated genes was correlated with tumor patient prognosis. Hub L1 ASP-associated genes CENPU and MCM2 showed a correlation with immune infiltration, clinical T stage, and cancer stemness in pan-cancer. Knockdown of L1 ASP-associated gene LINC00491 resulted in a significant decrease in tumor growth and migration ability.

Conclusions
The expression of L1 ASP-associated genes is significantly dysregulated at the pan-cancer level, which is closely related to the tumor microenvironment, progression, and patient prognosis. Hub genes CENPU and MCM2 are expected to be new tumor diagnostic markers and therapeutic targets.
TLR8 escapes X chromosome inactivation in human monocytes and CD4+ T cells
Authors: Youness Ali , Cenac Claire , Faz-López Berenice , Grunenwald Solange , Barrat Franck J. , Chaumeil Julie , Mejía José Enrique , Guéry Jean-Charles 
Published: September 2023

Abstract
Background
Human endosomal Toll-like receptors TLR7 and TLR8 recognize self and non-self RNA ligands, and are important mediators of innate immunity and autoimmune pathogenesis. TLR7 and TLR8 are, respectively, encoded by adjacent X-linked genes. We previously established that TLR7 evades X chromosome inactivation (XCI) in female immune cells. Whether TLR8 also evades XCI, however, has not yet been explored.

Method
In the current study, we used RNA fluorescence in situ hybridization (RNA FISH) to directly visualize, on a single-cell basis, primary transcripts of TLR7 and TLR8 relative to X chromosome territories in CD14+ monocytes and CD4+ T lymphocytes from women, Klinefelter syndrome (KS) men, and euploid men. To assign X chromosome territories in cells lacking robust expression of a XIST compartment, we designed probes specific for X-linked genes that do not escape XCI and therefore robustly label the active X chromosome. We also assessed whether XCI escape of TLR8 was associated with sexual dimorphism in TLR8 protein expression by western blot and flow cytometry.

Results
Using RNA FISH, we show that TLR8, like TLR7, evades XCI in immune cells, and that cells harboring simultaneously TLR7 and TLR8 transcript foci are more frequent in women and KS men than in euploid men, resulting in a sevenfold difference in frequency. This transcriptional bias was again observable when comparing the single X of XY males with the active X of cells from females or KS males. Interestingly, TLR8 protein expression was significantly higher in female mononuclear blood cells, including all monocyte subsets, than in male cells.

Conclusions
TLR8, mirroring TLR7, escapes XCI in human monocytes and CD4+ T cells. Co-dependent transcription from the active X chromosome and escape from XCI could both contribute to higher TLR8 protein abundance in female cells, which may have implications for the response to viruses and bacteria, and the risk of developing inflammatory and autoimmune diseases.
Evolving prion-like tau conformers differentially alter postsynaptic proteins in neurons inoculated with distinct isolates of Alzheimer’s disease tau
Authors: Hromadkova Lenka , Kim Chae , Haldiman Tracy , Peng Lihua , Zhu Xiongwei , Cohen Mark , de Silva Rohan , Safar Jiri G. 
Published: September 2023

Abstract
Objectives
Although accumulation of misfolded tau species has been shown to predict cognitive decline in patients with Alzheimer’s disease (AD) and other tauopathies but with the remarkable diversity of clinical manifestations, neuropathology profiles, and time courses of disease progression remaining unexplained by current genetic data. We considered the diversity of misfolded tau conformers present in individual AD cases as an underlying driver of the phenotypic variations of AD and progressive loss of synapses.

Methods
To model the mechanism of tau propagation and synaptic toxicity of distinct tau conformers, we inoculated wild-type primary mouse neurons with structurally characterized Sarkosyl-insoluble tau isolates from the frontal cortex of six AD cases and monitored the impact for fourteen days. We analyzed the accumulation rate, tau isoform ratio, and conformational characteristics of de novo-induced tau aggregates with conformationally sensitive immunoassays, and the dynamics of synapse formation, maintenance, and their loss using a panel of pre-and post-synaptic markers.

Results
At the same concentrations of tau, the different AD tau isolates induced accumulation of misfolded predominantly 4-repeat tau aggregates at different rates in mature neurons, and demonstrated distinct conformational characteristics corresponding to the original AD brain tau. The time-course of the formation of misfolded tau aggregates and colocalization correlated with significant loss of synapses in tau-inoculated cell cultures and the reduction of synaptic connections implicated the disruption of postsynaptic compartment as an early event.

Conclusions
The data obtained with mature neurons expressing physiological levels and adult isoforms of tau protein demonstrate markedly different time courses of endogenous tau misfolding and differential patterns of post-synaptic alterations. These and previous biophysical data argue for an ensemble of various misfolded tau aggregates in individual AD brains and template propagation of their homologous conformations in neurons with different rates and primarily postsynaptic interactors. Modeling tau aggregation in mature differentiated neurons provides a platform for investigating divergent molecular mechanisms of tau strain propagation and for identifying common structural features of misfolded tau and critical interactors for new therapeutic targets and approaches in AD.
Standardized approach for extubation during extracorporeal membrane oxygenation in severe acute respiratory distress syndrome: a prospective observational study
Authors: Roncon-Albuquerque Roberto , Gaião Sérgio , Vasques-Nóvoa Francisco , Basílio Carla , Ferreira Ana Rita , Touceda-Bravo Alberto , Pimentel Rodrigo , Vaz Ana , Silva Sofia , Castro Guiomar , Veiga Tiago , Martins Hélio , Dias Francisco , Pereira Catarina , Marto Gonçalo , Coimbra Isabel , Chico-Carballas Juan Ignacio , Figueiredo Paulo , Paiva José Artur 
Published: September 2023

Abstract
Background
Extubation during extracorporeal oxygenation (ECMO) in severe acute respiratory distress syndrome (ARDS) has not been well studied. Despite the potential benefits of this strategy, weaning from ECMO before liberation from invasive mechanical ventilation remains the most frequent approach. Our aim was to evaluate the safety and feasibility of a standardized approach for extubation during ECMO in patients with severe ARDS.

Results
We conducted a prospective observational study to assess the safety and feasibility of a standardized approach for extubation during ECMO in severe ARDS among 254 adult patients across 4 intensive care units (ICU) from 2 tertiary ECMO centers over 6 years. This consisted of a daily assessment of clinical and gas exchange criteria based on an Extracorporeal Life Support Organization guideline, with extubation during ECMO after validation by a dedicated intensive care medicine specialist. Fifty-four (21%) patients were extubated during ECMO, 167 (66%) did not reach the clinical criteria, and in 33 (13%) patients, gas exchange precluded extubation during ECMO. At ECMO initiation, there were fewer extrapulmonary organ dysfunctions (lower SOFA score [OR, 0.88; 95% CI, 0.79–0.98; P = .02] with similar PaO2/FiO2) when compared with patients not extubated during ECMO. Extubation during ECMO associated with shorter duration of invasive mechanical ventilation (7 (4–18) vs. 32 (18–54) days; P < .01) and of ECMO (12 (7–25) vs. 19 (10–41) days; P = .01). This was accompanied by a lower incidence of hemorrhagic shock (2 vs. 11%; P = .05), but more cannula-associated deep vein thrombosis (49 vs. 31%; P = .02) and failed extubation (20 vs. 6%; P < .01). There were no increased major adverse events. Extubation during ECMO is associated with a lower risk of all-cause death, independently of measured confounding (adjusted logistic regression OR 0.23; 95% confidence interval 0.08–0.69, P = .008).

Conclusions
A standardized approach was safe and feasible allowing extubation during ECMO in 21% of patients with severe ARDS, selecting patients who will have a shorter duration of invasive mechanical ventilation, ECMO course, and ICU stay, as well as fewer infectious complications, and high hospital survival.
Approximation by multivariate Baskakov–Durrmeyer operators in Orlicz spaces
Authors: Han Ling-Xiong , Bai Yu-Mei , Qi Feng 
Published: September 2023

AbstractEmploying some properties of multivariate Baskakov–Durrmeyer operators and utilizing modified K-functional and a decomposition technique, the authors obtain the direct theorem and weak type inverse theorem in the Orlicz spaces.
Discrepancies between media portrayals and actual demographics of eating disorders in TV and film: implications of representation
Authors: Bassett Lucy , Ewart Maya 
Published: September 2023

Abstract
Background
Media has a reputation for painting a narrow, simplistic, sensationalized portrait of eating disorders. There is little analysis of how film and TV portray eating disorders nor the implications of this representation. This study fills that gap by comparing demographics of US film and TV characters since the 1980s to actual population demographics of people with eating disorders.

Methods
We compiled a dataset of TV and movie characters with eating disorders and categorized characters’ gender, age, race/ethnicity, and sexual orientation. We narrowed the dataset to include only US media depictions to facilitate comparisons with empirical prevalence, resulting in a total of 66 characters over the period 1981 to 2022. We then compared the demographic characteristics of our sample to national statistics on eating disorder prevalence.

Results
US media depictions of eating disorders overrepresented characters who were heterosexual (75.56%), White (84.85%), women (89.39%), and under age 30 (84.85%). This does not accurately reflect the populations experiencing eating disorders in the US.

Conclusions
Eating disorders have an image problem. TV and movies inaccurately portray them as primarily affecting heterosexual, White, women under age 30. Misrepresentation could fuel existing stigmas that inhibit individuals with eating disorders from seeking and receiving treatment. It could also perpetuate stereotypes that fuel misperceptions of the disease by medical providers, families, and policymakers. We recommend more accurate representation in the media to better reflect current demographics and increase awareness of the range of people who can experience eating disorders.
What do we know about the sleep effects of caffeine used to treat apnoea of prematurity? A systematic review of the literature
Authors: de Toledo Ana Renata Pinto , Caetano Higor Arruda , Skupien Jovito Adiel , Boeck Carina Rodrigues , Fiori Humberto , da Silva Rosane Souza 
Published: September 2023

Abstract
Objective
Scientific scrutiny has proved the safety and benefits of caffeine to treat apnoea of prematurity (AOP). However, there is no consensus on the effects of this treatment on sleep, especially considering the key role of adenosine and early brain development for sleep maturation. We systematically reviewed studies with sleep as a primary and/or secondary outcome or any mention of sleep parameters in the context of caffeine treatment for AOP.

Methods
We performed a systematic search of PubMed, Web of Science and the Virtual Health Library from inception to 7 September 2022 to identify studies investigating the short- and long-term effects of caffeine to treat AOP on sleep parameters. We used the PIC strategy considering preterm infants as the Population, caffeine for apnoea as the Intervention and no or other intervention other than caffeine as the Comparison. We registered the protocol on PROSPERO (CRD42021282536).

Results
Of 4019 studies, we deemed 20, including randomised controlled trials and follow-up and observational studies, to be eligible for our systematic review. The analysed sleep parameters, the evaluation phase and the instruments for sleep assessment varied considerably among the studies. The main findings can be summarised as follows: (i) most of the eligible studies in this systematic review indicate that caffeine used to treat AOP seems to have no effect on key sleep parameters and (ii) the effects on sleep when caffeine is administered earlier, at higher doses or for longer periods than the most common protocol have not been investigated. There is a possible correlation between the caffeine concentration and period of exposure and negative sleep quality, but the sleep assessment protocols used in the included studies did not have high-quality standards and could not provide good evidence.

Conclusions and implications
Sleep quality is an important determinant of health, and better investments in research with adequate sleep assessment tools are necessary to guarantee the ideal management of children who were born preterm.
Acute and long-term psychosocial consequences in grandparents when a grandchild is diagnosed with cancer – the GROKids Project: a population-based mixed-methods study protocol
Authors: Michel Gisela , Raguindin Peter Francis , Priboi Cristina , Ilic Anica , Holmer Pauline , Scheinemann Katrin ,   the GROKids Project, von der Weid Nicolas , Brazzola Pierluigi , Roessler Jochen , Ansari Marc , Diezi Manuel , Beck-Popovic Maja , Schilling Freimut , Greiner Jeanette , Hengartner Heinz 
Published: September 2023

Abstract
Background
Grandparents play a crucial role in providing their families with love, support, and wisdom, often also supporting them in practical and financial ways. The psychosocial effects experienced by grandparents when a grandchild is diagnosed with an illness can be significant, including increased stress, anxiety, grief, and disruptions in their own lives. Yet, the experience of grandparents is often overlooked in the literature.

Methods/design
The GROKids Project aims to investigate how grandparents are affected by a grandchild's cancer diagnosis. It employs a mixed-methods approach and consists of three studies: a longitudinal cohort study (Study 1) and a qualitative study (Study 2) involving grandparents of children with a recent cancer diagnosis, and a cross-sectional study (Study 3) of grandparents of childhood cancer survivors. Study 1 covers four time points over two years after the cancer diagnosis, while Study 2 explores the lived experiences of a subsample of these grandparents. Study 3 collects data from grandparents of childhood cancer survivors diagnosed 3 to 10 years ago. Participants are recruited across eight pediatric oncology centers in Switzerland, and through patient advocacy and support groups. Eligibility criteria include having a grandchild diagnosed with cancer and being fluent in German, French, or Italian.
Study procedures involve requesting grandparents’ contacts from eligible families, and later contacting grandparents, providing study information, obtaining informed consent, and sending out questionnaires by post or online. Reminder calls and mails are used to improve response rates. Data analysis includes multilevel regression (Study 1), thematic analysis (Study 2), and regression analyses (Study 3). Various validated questionnaires are used to assess physical health and overall well-being, psychological health, internal, and external factors.

Discussion
This project addresses the gaps in understanding the psychosocial effects on grandparents having a grandchild diagnosed with cancer. It utilizes a comprehensive approach, including multiple methodologies and considering the broader family context. The project’s strengths lie in its mixed-methods design, longitudinal approach, and inclusion of the perspectives of the sick children, siblings, and parents, besides grandparents. By gaining a more profound understanding of grandparents' experiences, researchers and healthcare professionals can develop targeted interventions and support services to address grandparents’ unique needs.