bluuebunny/crossref_metadata_2025_split huggingface dataset:
Low-Molecular Neurotrophin-3 Mimetics with Different Patterns of Postreceptor Signaling Activation Attenuate Differentially Morphine Withdrawal in Rats
Authors: Kolik Larisa G. , Konstantinipolsky Mark A. , Nikolaev Sergey V. , Logvinov Ilya O. , Antipova Tatyana A. , Gudasheva Tatiana A. 
Published: December 2024

Abstract
The accumulated evidence suggests that varying levels of tyrosine kinase receptor signaling pathway activity may regulate opiate-associated neuroadaptation of noradrenergic system. Neurotrophin-3 (NT-3) interacts with tropomyosin receptor kinases (TRKs), binding mainly to TRKC receptors, which are expressed within noradrenergic neurons in the blue spot (locus coeruleus, LC). Considering the difficulties in delivering full-length neurotrophins to the CNS after systemic administration, low-molecular mimetics of loop 4 in NT-3, hexamethylenediamide bis-(N-monosuccinyl-L-asparaginyl-L-asparagine) (GTS-301), and hexamethylenediamide bis-(N-γ-oxybutyryl-L-glutamyl-L-asparagine) (GTS-302), activating TRKC and TRKB receptors, were synthesized. The aim of the study is comparative examination of the effects of NT-3 dipeptide mimetics on the signs of morphine withdrawal in outbred white rats with opiate dependence, as well as investigation of activation of postreceptor signaling pathways by the mimetics. Dipeptides GTS-301 and GTS-302 after acute administration at doses of 0.1, 1.0, and 10.0 mg/kg (i.p., intraperitoneal) had a dose-dependent effect on the specific morphine withdrawal symptoms with the most effective dose being 1.0 mg/kg. Maximum decrease in the total index of morphine withdrawal syndrome for GTS-301 was 31.3% and for GTS-302 – 41.4%. Unlike GTS-301, GTS-302 weakened mechanical allodynia induced by morphine withdrawal, reducing tactile sensitivity. When studying activation of the postreceptor signaling pathways by the NT-3 mimetics in the HT-22 hippocampal cell culture, a different pattern of postreceptor signaling was shown: GTS-302 (10−6 M), similar to NT-3, activates all three MAPK/ERK, PI3K/AKT/mTOR, and PLCγ1 pathways, while GTS-301 (10−6 M) triggers only MAPK/ERK and PLCγ1 pathways. Thus, the identified features of attenuation of the morphine withdrawal syndrome in the rats under GTS-301 and GTS-302 effects could be associated with different activation pattern of the postreceptor pathways.
Pulmonary artery peak Doppler velocity as an estimator of systemic blood flow and predictor of intraventricular haemorrhage in preterm infants: a multicentre prognostic accuracy study
Authors: Terroba-Seara Sandra , Oulego-Erroz Ignacio , Palanca-Arias Daniel , Galve-Pradel Zenaida , Delgado-Nicolás Sara , Pérez-Pérez Alicia , Rodríguez-Ozcoidi Jorge , Lavilla-Oíz Ana , Bravo María Carmen , La Banda-Montalvo Leticia , Méndez-Abad Paula , Zafra-Rodríguez Pamela , Rodeño Fernandez Lorena , Montero-Gato Jon , Bustamante-Hervás Carmen , Vega-Del-Val Cristina , Rodríguez-Fanjul Javier , Mayordomo-Colunga Juan , Alegría-Echauri Iosune 
Published: December 2024

Objectives(1) To assess how main pulmonary artery peak Doppler velocity (MPAVpeak) correlates with right ventricular output (RVO) and superior vena cava flow (SVCf), (2) to assess the reproducibility of MPAVpeak and (3) to test the prognostic accuracy of MPAVpeak to predict high-grade intraventricular haemorrhage (IVH) or death at seventh day of life.DesignProspective cohort study.SettingNine third-level neonatal units in Spain.PatientsPreterm infants <33 weeks of gestational age who had standardised measurements of MPAVpeak, RVO and SVCf at 6, 12 and 24 hours of life.Main outcome measuresHigh-grade IVH or death at seventh day of life.ResultsOne hundred and ninety preterm infants with a median (IQR) gestational age and birth weight of 29.7 weeks (27.1–31.8) and 1152 g (892–1491), respectively, were included. High-grade IVH or death at seventh day of life occurred in 24 (12.6%). MPAVpeak was strongly correlated with RVO (Spearmanrho0.826–0.843). MPAVpeak discriminated well for low RVO (<120 mL/kg/min) at 6 (AUROC, area under the receiver operating characteristic curve=0.90), 12 (AUROC 0.94) and 24 hours (AUROC 0.86). Observer reproducibility was better for MPAVpeak (inter-observer limits of agreement ±8.4%) compared with RVO (±18.8%) and SVCf (±32.2%). The prognostic accuracy of MPAVpeak to predict high-grade IVH or death was good (AUROC >0.75) and non-inferior to RVO and SVCf (DeLong’s test p>0.05).ConclusionsMPAVpeak is an adequate marker of systemic blood flow with high reproducibility and acceptable prognostic accuracy in preterm infants below 33 weeks of gestational age during the first day of life.
Outcomes of staged conjunctival flap and corneal transplantation for infectious keratitis resistant to medical treatment
Authors: Kilian Raphael , Pellegrini Marco , Yu Angeli Christy , de Ruvo Valentino , Salgari Niccolò , Busin Massimo 
Published: December 2024

Background/AimsTo explore the outcomes of conjunctival flap (CF) followed by keratoplasty in patients with severe infectious keratitis (IK) unresponsive to medical treatment.MethodsThis is a retrospective monocentric study including 29 eyes of 29 patients with IK resistant to antibiotic treatment associated with stromal ulcer deepening to ≥50% of corneal thickness. All eyes underwent Gundersen’s CF procedure and penetrating keratoplasty (PK), deep anterior lamellar keratoplasty (DALK) or mushroom keratoplasty (MK), at least 4 months thereafter. Outcome measures included corrected distance visual acuity (CDVA), endothelial cell count (ECC), graft survival and complications.ResultsIK healed in all eyes following CF. The mean time interval between CF and keratoplasty was 16.3±16.1 months. 55% of patients underwent PK, 35% MK and 10% DALK. Mean follow-up duration was 39.6±34.3 months. At the last available follow-up, a CDVA≥20/200 was obtained in 50%, 33.3% and 70% of cases, respectively after PK, DALK and MK. Mean annual endothelial cell loss was 24.5% following PK and 10.7% following MK. Overall, graft failure occurred in 75% of cases after PK, 100% after DALK and 20% after MK. The most frequent complications were endothelial decompensation without immunological rejection (34.5%, after 31.1±25.1 months) and graft rejection (17.2%, after 10.2±7.9 months, all in the PK group).ConclusionCF surgery followed by staged keratoplasty represents an alternative therapeutic approach to avoid high-risk keratoplasty ‘a chaud’ in cases of severe IK.
RESILIENCE (Retrospective Linkage Study of Autoimmune Encephalitis): protocol for an Australian retrospective cohort study of outcomes in autoimmune encephalitis using data linkage techniques
Authors: Halliday Amy Jean , Lambert Katrina , Bundell Christine , McLean-Tooke Andrew , Gillis David , Prain Kerri M , Bryson Greg , Gillinder Lisa , Brown David , Ramanathan Sudarshini , Dale Russell , Brilot Fabienne , Jordan Nerissa , Lawn Nicholas , Lai Alan , Boyd James ,   Australian Adult Comprehensive Epilepsy Centres Consortium, Camacho Ximena , D’Souza Wendyl Jude 
Published: December 2024

IntroductionThe autoimmune encephalitides (AE) are a heterogeneous group of neurological disorders with significant morbidity and healthcare costs. Despite advancements in understanding their pathophysiology, uncertainties persist regarding long-term prognosis and optimal management. This study aims to address these gaps, focusing on immunotherapeutic strategies, neoplastic associations and functional outcomes.Methods and analysisThe Retrospective Linkage Study of Autoimmune Encephalitis project will use data linkage techniques to establish a retrospective 10-year population cohort of Australian patients with AE. Two cohorts will be analysed, the Reference Cohort (clinically confirmed AE cases obtained from hospital medical records, n=145) and the Operationally Defined Cohort (AE cases identified through administrative coding data, n≈5000). Univariate statistical methods will identify candidate coding elements for use in the operational case definition and multivariate models and evaluation methods used to identify and internally validate the optimal coding algorithms. The two study cohorts will be analysed separately due to the high likelihood of overlap. Primary outcomes include relapse rate, prevalence and control of epilepsy, cognitive disability, poor educational attainment, delayed tumour diagnosis and mortality. Statistical analyses, including random mixed-effects regression models, will assess treatment effects, covariates and outcomes.Ethics and disseminationThis project has been approved by the leading investigators’ institutional Human Research Ethics Committee (HREC), the St Vincent’s Hospital Melbourne HREC, as well as the Australian Institute of Health and Welfare HREC and relevant jurisdictional HRECs where required. The dissemination of findings through peer-reviewed publications and patient advocacy channels will maximise the impact of this research.
Factors associated with declining a menstrual cup among female students and their parents in Ugandan secondary schools: a cross-sectional study
Authors: Mugenyi Levicatus , Tembo Mandikudza , Nelson Kate Andrews , Thomas Katherine A , Kansiime Catherine , Lagony Stephen , Mpaata Alex Muleyi , Belfield Sophie , Nakalema Shamirah , Akech Agnes , Torondel-Lopez Belen , Weiss Helen A 
Published: December 2024

IntroductionA greater choice of menstrual products may improve menstrual health (MH). This study assessed factors associated with declining consent to receive a menstrual cup by parents and female students participating in a MH intervention trial in Ugandan schools.MethodsWe analysed baseline data from a cluster-randomised trial evaluating the effectiveness of a multicomponent MH intervention among female students in 60 Ugandan secondary schools. Parental consent and student assent to receive a menstrual cup and training on its use was sought separately from consent from other trial activities. Random-effects logistic regression models were used to estimate adjusted OR (aOR) and 95% CIs for factors associated with (i) parents or guardians declining the cup and (ii) students declining the cup using hierarchical conceptual frameworks.ResultsThe baseline trial population comprised 3705 post-menarchal students (mean age 15.6 (SD 0.9 years), of whom 2048 (55.3%) were day students. Among the parents of the 3635 participants aged <18 years, 1566 (43.1%) declined consent for their student to receive the cup. This was higher in Wakiso District than in Kalungu District (52.9% vs 8.0%, p<0.001). Parental decline of the cup differed by ethnicity, and this association varied between districts (p=0.004). Overall, 20.5% students declined the cup (Kalungu 21.1%, Wakiso 20.2%, p=0.62). Student decline of the cup was higher among day than boarding students (aOR=1.40, 95% CI 1.07 to 1.84), those with academic performance above the median score (aOR=1.29, 95% CI 1.01 to 1.65), those whose menstrual practice needs score was above the median (aOR=1.36, 95% CI 1.08 to 1.72) and those with more negative attitudes to MH (aOR=1.46, 95% CI 1.16 to 1.83).ConclusionAmong Ugandan students and their parents, declining consent to receive a menstrual cup varied by district and ethnicity as well as academic performance and menstrual-related factors. A contextual understanding of the barriers for uptake of the menstrual cup is needed to guide future interventions.Trial registration numberISRCTN45461276.
Systematic review of prognostic models for predicting recurrence and survival in patients with treated oropharyngeal cancer
Authors: Dretzke Janine , Abou-Foul Ahmad K , Albon Esther , Hillier Bethany , Scandrett Katie , Price Malcolm J , Moore David J , Mehanna Hisham , Nankivell Paul 
Published: December 2024

ObjectivesThis systematic review aims to evaluate externally validated models for individualised prediction of recurrence or survival in adults treated with curative intent for oropharyngeal cancer.DesignSystematic review.SettingHospital care.MethodsSystematic searches were conducted up to September 2023 and records were screened independently by at least two reviewers. The Prediction model Risk Of Bias ASsessment Tool was used to assess risk of bias (RoB). Model discrimination measures (c-indices) were presented in forest plots. Clinical and methodological heterogeneity precluded meta-analysis.ResultsFifteen studies developing and/or evaluating 25 individualised risk prediction models were included. The majority (77%) of c-indices for model developments and validations were ≥0.7 indicating ‘good’ discriminatory ability for models predicting overall survival. For disease-specific measures, most (73%) c-indices for model development were also ≥0.7, but fewer (40%) were ≥0.7 for external validations. Comparisons across models and outcome measures were hampered by heterogeneity. Only two studies directly compared models in the same cohort. Since all models were subject to a high RoB, primarily due to concerns with the analysis, the trustworthiness of the findings remains uncertain. Concerns included a lack of accounting for potentially missing data, model overfitting or competing risks as well as small event numbers. There were fewer concerns related to the participant, predictor and outcome domains, although reporting was not always detailed enough to make an informed decision. Where human papilloma virus (HPV) status and/or a radiomics score were included as a variable, models had better discriminative ability.ConclusionsThere were no models assessed as being at low RoB. Given that HPV status or a radiomics score appeared to improve model discriminative performance, further external validation of existing models to assess generalisability should focus on models that include HPV status as a variable. Development and validation of future models should be considered in HPV+ or HPV− cohorts separately to ensure representativeness.PROSPERO registration numberCRD42021248762.
Association of sarcopenia, ambient air pollution and cognitive function in a community-dwelling middle-aged and elderly Korean population: a community-based cohort study
Authors: Lee Jane J , Woo Hae Dong , Kim Ji Hyun , Jung Eun Ju , Lee Kyoungho 
Published: December 2024

ObjectivesTo investigate the association of sarcopenia, exposure to medium-term to long-term ambient particulate matter 2.5 µm and 10 µm (PM2.5and PM10) pollution and cognitive function in a community-dwelling cohort of middle-aged and older adults in South Korea.DesignA community-based prospective cohort study.SettingIn the Korean Genome and Epidemiology Study (KoGES).ParticipantsThe participants were drawn from the seventh follow-up visit conducted between 2015 and 2016 in the KoGES community-based Ansung cohort who had participated in an ageing substudy.Outcome measuresCognitive function was evaluated by the Korean version of the Mini-Mental State Examination (K-MMSE) and decreased cognitive function was defined as a K-MMSE score of 23 or less.ResultsOf the 2274 participants (mean age 70.1 years, 58.3% women and mean annual PM2.5and PM10levels of 30.7 and 52.2 μg/m3, respectively), 8.7% (n=197) were sarcopenic, 35.8% (n=814) were possible sarcopenic and 55.5% (n=1263) were non-sarcopenic. The predictors of sarcopenia included body mass index, cognitive function, age, marital status, hypertension and physical activity. Exposure to PM2.5and PM10for an average duration of 1 month to 3 years was not selected as a predictor of sarcopenia. Participants with sarcopenia were associated with lower cognitive scores (β=−1.51, p<0.0001) and decreased cognitive function compared with those without sarcopenia (OR 2.34, 95% CI 1.56 to 3.52). Exposure to medium-term and long-term PM2.5or PM10was not associated with sarcopenia. The effect modification of PM exposure on the association between sarcopenia and cognitive function was generally not detected.ConclusionsIn this community-based observational cohort study of KoGES participants aged 50 years and older, sarcopenia was associated with decreased cognitive function. However, medium-term to long-term exposure to PM2.5or PM10was not associated with sarcopenia and did not modify the relationship between sarcopenia and cognitive function.
Phase I-IIa clinical trial to evaluate the safety, feasibility and efficacy of the use of a palate mucosa generated by tissue engineering for the treatment of children with cleft palate: the BIOCLEFT study protocol
Authors: España-López Antonio , Fernández-Valadés Ricardo , Cubiles Elisa , Garzón Ingrid , Martin-Piedra Miguel Angel , Carriel Víctor , Campos Fernando , Martínez-Plaza Adoración , Vallejo Daniel , Liceras-Liceras Esther , Chato-Astrain Jesús , García-García Oscar Dario , Sánchez-Porras David , Ávila-Fernández Paula , Etayo-Escanilla Miguel , Quijano Blanca , Aguilar Elisabet , Campos Antonio , Carmona Gloria , Alaminos Miguel 
Published: December 2024

IntroductionThe current gold standard treatment for patients with orofacial clefts is surgical repair of the palatal defect (uranostaphylorrhaphy), which is associated with growth defects and hypoplasia of the maxillofacial structures. This trial aims to evaluate the potential of a bioengineered artificial palate mucosa, created through tissue engineering with autologous stromal and epithelial cells and nanostructured fibrin–agarose biomaterials, to enhance treatment outcomes for patients with unilateral cleft lip and palate.Methods and analysisThis phase I-IIa clinical trial aims to evaluate the feasibility and biosafety of a procedure involving grafting bioartificial palate mucosa onto the areas of denudated bone in patients undergoing uranostaphylorrhaphy. The control patients will undergo standard surgical treatment. Five patients will be included in the first biosafety phase. In the second phase, 10 patients will be randomly assigned to the intervention or control group (1:1). The intervention group will undergo standard surgical treatment followed by the application of autologous bioartificial palate mucosa. Feasibility will be analysed at the time of surgery. Nine postimplant visits will be scheduled over a 2-year follow-up period, in which local and systemic biosafety will be investigated by determining graft evolution, including signs of necrosis, rejection, inflammation and patient factors. Preliminary signs of efficiency will be explored by sequentially evaluating craniomaxillofacial development, hearing impairment, speech capability and quality of life of the family. The research will be published in journals and posted in the relevant repositories when available.Ethics and disseminationThis study has been approved by the Committee of Ethics in Research with Medicinal Products (CEIm) and authorised by the Spanish Medicines Agency (AEMPS). The results of this study will be published in peer-reviewed journals.Trial registration numberNCT06408337; ClinicalTrials.gov: EuclinicalTrials. eu: 2023-506913-23-00.
Kindness: Poor cousin or equal kin to Compassion and Empathy in the Healthcare Literature? A Scoping Review
Authors: Macklin Nicki , Wilkinson-Meyers Laura , Dowell Anthony 
Published: December 2024

ObjectiveThis scoping review seeks to understand how kindness, compassion and empathy are defined and conceptualised within existing healthcare services literature.IntroductionLittle consensus exists on how healthcare literature defines and conceptualises kindness. Kindness is often conflated with the terms compassion and empathy, which both have more prominence in the literature. However, evidence would suggest that all three terms are indeed different. To advance kindness as a key tenet of quality improvement and human experience outcomes in healthcare, a consensual definition must be established in the evidence base.MethodsWe reviewed published research identified using search queries across five databases and one search engine. Studies were included in this review if the definition, measurement and/or conceptualisation of kindness, empathy and/or compassion were stated objectives of the work and the research was directly relevant to healthcare settings.Results1348 results were screened, and with additional snowballing of some articles for relevant references, 107 progressed to full-text screening. Forty-two articles were subsequently included in this scoping review. By synthesising this evidence, we establish key commonalities and differences for kindness, compassion and empathy. We present a model for understanding how empathy, compassion and kindness can be viewed on a stimulus–response–action continuum. We also explore the definitional challenges expressed by many authors who call for these terms to be treated as separate concepts.ConclusionsThis review evidence demonstrates that kindness, compassion and empathy have clear themes that stand them apart, and they occupy different places on the stimulus–response–action continuum. Importantly, kindness deserves its own place in literature as a primary concept, not as a second tier to compassion or empathy. By comparing each term, these positions are now highlighted. They can help us to more articulately define, conceptualise and value kindness, compassion and empathy for their unique contributions to the humanity of healthcare
Self-collected penile-meatal swabs are suitable for the detection of STIs in Ugandan men with high rates of STI coinfections
Authors: Melendez Johan H , Muñiz Tirado Adamaris , Onzia Annet , Mande Emmanuel , Hardick Justin P , Parkes-Ratanshi Rosalind , Hamill Matthew M , Manabe Yukari C 
Published: December 2024

BackgroundSexually transmitted infections (STIs) are a global health challenge. Testing is not routinely performed in low- and middle-income countries (LMICs), which bear a disproportionate burden of STIs. Self-collected penile-meatal swabs (SCPMS) are an alternative to urine for STI testing, but data from LMICs are limited.MethodsBetween October 2019 and September 2020, recruited participants with urethral discharge syndrome at government health facilities in Kampala, Uganda, provided urine and SCPMS. Samples were retrospectively analysed forChlamydia trachomatis(CT),Neisseria gonorrhoeae(NG),Mycoplasma genitalium(MG) andTrichomonas vaginalis(TV) using Aptima assays. Paired SCPMS and urine samples with discordant STI results were analysed using real-time PCR assays.ResultsOf the 250 participants, 66.8% (n=167), 22.8% (n=57), 12.8% (n=32) and 2.4% (n=6) tested positive for NG, CT, MG and TV, respectively, on testing of their SCPMS and urine samples. The overall agreement between urine and SCPMS for all STIs using the Aptima assays was 98.7% (987/1000). After adjudication with PCR assays, the agreement between urine and SCPMS for NG, CT, MG and TV was 100% (250/250), 97.6% (244/250), 99.6% (249/250), and 99.6% (249/250), respectively. There was no significant difference between SCPMS and urine (p=0.9996). For paired samples with one STI (n=164) or ≥2 STIs (n=39), concordance was 100% (656/656) and 97.2% (175/180), respectively. There was no association between number of STIs and agreement between sample types (p=0.8606).ConclusionsThis study revealed a high level of agreement between SCPMS and urine for detection of STIs in symptomatic Ugandan men, even in the presence of multiple concurrent STIs. SCPMS may be a suitable alternative to urine, with ease of collection, transporting, and processing of samples.