bluuebunny/crossref_metadata_2025_split huggingface dataset:
A systematic review of the protective effects of silymarin/silibinin against doxorubicin-induced cardiotoxicity
Authors: Singh Mandeep , Kadhim Mustafa M. , Turki Jalil Abduladheem , Oudah Shamam Kareem , Aminov Zafar , Alsaikhan Fahad , Jawhar Zanko Hassan , Ramírez-Coronel Andrés Alexis , Farhood Bagher 
Published: May 2023

AbstractPurposeAlthough doxorubicin chemotherapy is commonly applied for treating different malignant tumors, cardiotoxicity induced by this chemotherapeutic agent restricts its clinical use. The use of silymarin/silibinin may mitigate the doxorubicin-induced cardiac adverse effects. For this aim, the potential cardioprotective effects of silymarin/silibinin against the doxorubicin-induced cardiotoxicity were systematically reviewed.MethodsIn this study, we performed a systematic search in accordance with PRISMA guideline for identifying all relevant studies on “the role of silymarin/silibinin against doxorubicin-induced cardiotoxicity” in different electronic databases up to June 2022. Sixty-one articles were obtained and screened based on the predefined inclusion and exclusion criteria. Thirteen eligible papers were finally included in this review.ResultsAccording to the echocardiographic and electrocardiographic findings, the doxorubicin-treated groups presented a significant reduction in ejection fraction, tissue Doppler peak mitral annulus systolic velocity, and fractional shortening as well as bradycardia, prolongation of QT and QRS interval. However, these echocardiographic abnormalities were obviously improved in the silymarin plus doxorubicin groups. As well, the doxorubicin administration led to induce histopathological and biochemical changes in the cardiac cells/tissue; in contrast, the silymarin/silibinin co-administration could mitigate these induced alterations (for most of the cases).ConclusionAccording to the findings, it was found that the co-administration of silymarin/silibinin alleviates the doxorubicin-induced cardiac adverse effects. Silymarin/silibinin exerts its cardioprotective effects via antioxidant, anti-inflammatory, anti-apoptotic activities, and other mechanisms.
Maternal and congenital syphilis in Indigenous Peoples: a scoping review of the worldwide literature
Authors: Cardoso Andrey Moreira , Caldas Aline Diniz Rodrigues , Oliveira Evelin Santos , Paixão Enny Santos , Soares Maria Auxiliadora Santos , dos Santos Idália Oliveira , Barreto Maurício Lima , Ichihara Maria Yury Travassos 
Published: May 2023

Abstract
Background
Syphilis is among the most common sexually transmitted infections worldwide. When it occurs during pregnancy, it can seriously affect the fetus and newborn`s health. The scarcity of studies on maternal and congenital syphilis in Indigenous Peoples remains an obstacle to its control in these populations. This study aimed to explore the breadth of the literature, map updated evidence, and identify knowledge gaps on maternal and congenital syphilis in Indigenous Peoples worldwide.

Methods
We conducted a Scoping review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses - Extension for Scoping Reviews. In March 2021, we collected data through a priority search on PubMed, Web of Science, Embase, and SciELO.

Results
The strategy yielded 24 studies for analysis. Data in the articles were collected from 1989 to 2020, half from 2015 onwards. Studies were in Oceania and the Americas, mainly in South America (66.7%), particularly in Brazil (50.0%). The topics assessed were Data quality related to maternal and congenital syphilis (20.8%); Diagnosis, provision, access, and use of health services (62.5%); Disease frequency and health inequities (54.2%); Determinants of maternal syphilis and congenital syphilis (20.8%); and Outcomes of maternal and congenital syphilis in the fetus (20.8%). The results show that the available literature on maternal and congenital syphilis is sparse and concentrated in some geographic areas; the frequency of these diseases in Indigenous Peoples varies but is generally higher than in the non-indigenous counterparts; the quality of surveillance data and health information systems is poor; multiple healthcare barriers exist; and the diversity of terms to identify Indigenous Peoples is a challenge to mapping scientific outputs on Indigenous Peoples’ health.

Conclusions
Maternal and congenital syphilis in Indigenous Peoples is a double-neglected condition and research in this area should be given the priority and encouragement it deserves globally. Reliable data and improving access to health care are needed to reduce the burden of syphilis and correctly inform policies and health services response to mitigate ethnic-racial inequalities in maternal and congenital syphilis.
The impact of JUUL market entry on cigarette sales: evidence from a major chain retailer in Canada
Authors: Xu Yingying , Sen Anindya , Chen Tengjiao , Harris Christopher M. , Prakash Shivaani 
Published: May 2023

Abstract
Background
Electronic nicotine delivery systems (ENDS), such as the JUUL system, are nicotine products for adults who currently smoke cigarettes but are looking for an alternative to combustible cigarettes. Sales of ENDS products were legislatively acknowledged and authorized federally in Canada with the Royal Assent of the Tobacco and Vaping Products Act in 2018.

Methods
With the unique dataset from a major chain retailer in Canada, we evaluated the impacts of JUUL market entry on cigarette sales across Canada from January 2017 to August 2019 using two-way fixed effects panel regression models by leveraging on the entry time variation at the city level. We conducted various robustness checks and a permutation test to validate our results.

Results
Our estimates suggested that JUUL market entry was, on average, significantly correlated with a 1.65% per-month decrease in cigarette sales during the initial months, and with a potentially larger impact on urban areas. Our results were robust across various specifications and tests. These findings implied that JUUL and combustible cigarettes act as economic substitutes during the study time period in Canada.

Conclusions
These results suggested that local availability of ENDS products, such as JUUL, has the potential to reduce local cigarette consumption.
Cardiomyocyte-targeting exosomes from sulforaphane-treated fibroblasts affords cardioprotection in infarcted rats
Authors: Papini Gaia , Furini Giulia , Matteucci Marco , Biemmi Vanessa , Casieri Valentina , Di Lascio Nicole , Milano Giuseppina , Chincoli Lucia Rosa , Faita Francesco , Barile Lucio , Lionetti Vincenzo 
Published: May 2023

Abstract
Background
Exosomes (EXOs), tiny extracellular vesicles that facilitate cell–cell communication, are being explored as a heart failure treatment, although the features of the cell source restrict their efficacy. Fibroblasts the most prevalent non-myocyte heart cells, release poor cardioprotective EXOs. A noninvasive method for manufacturing fibroblast-derived exosomes (F-EXOs) that target cardiomyocytes and slow cardiac remodeling is expected. As a cardioprotective isothiocyanate, sulforaphane (SFN)-induced F-EXOs (SFN-F-EXOs) should recapitulate its anti-remodeling properties.

Methods
Exosomes from low-dose SFN (3 μM/7 days)-treated NIH/3T3 murine cells were examined for number, size, and protein composition. Fluorescence microscopy, RT-qPCR, and western blot assessed cell size, oxidative stress, AcH4 levels, hypertrophic gene expression, and caspase-3 activation in angiotensin II (AngII)-stressed HL-1 murine cardiomyocytes 12 h-treated with various EXOs. The uptake of fluorescently-labeled EXOs was also measured in cardiomyocytes. The cardiac function of infarcted male Wistar rats intramyocardially injected with different EXOs (1·1012) was examined by echocardiography. Left ventricular infarct size, hypertrophy, and capillary density were measured.

Results
Sustained treatment of NIH/3T3 with non-toxic SFN concentration significantly enhances the release of CD81 + EXOs rich in TSG101 (Tumor susceptibility gene 101) and Hsp70 (Heat Shock Protein 70), and containing maspin, an endogenous histone deacetylase 1 inhibitor. SFN-F-EXOs counteract angiotensin II (AngII)-induced hypertrophy and apoptosis in murine HL-1 cardiomyocytes enhancing SERCA2a (sarcoplasmic/endoplasmic reticulum Ca2+ ATPase 2a) levels more effectively than F-EXOs. In stressed cardiomyocytes, SFN-F-EXOs boost AcH4 levels by 30% (p < 0.05) and significantly reduce oxidative stress more than F-EXOs. Fluorescence microscopy showed that mouse cardiomyocytes take in SFN-F-EXOs ~ threefold more than F-EXOs. Compared to vehicle-injected infarcted hearts, SFN-F-EXOs reduce hypertrophy, scar size, and improve contractility.

Conclusions
Long-term low-dose SFN treatment of fibroblasts enhances the release of anti-remodeling cardiomyocyte-targeted F-EXOs, which effectively prevent the onset of HF. The proposed method opens a new avenue for large-scale production of cardioprotective exosomes for clinical application using allogeneic fibroblasts.
12-week combined strength and endurance exercise attenuates CD8+ T-cell differentiation and affects the kynurenine pathway in the elderly: a randomized controlled trial
Authors: Boßlau Tim Konstantin , Wasserfurth Paulina , Reichel Thomas , Weyh Christopher , Palmowski Jana , Nebl Josefine , Joisten Niklas , Belen Sergen , Schenk Alexander , Hahn Andreas , Zimmer Philipp , Krüger Karsten 
Published: May 2023

AbstractBackgroundAge-related accumulation of highly differentiated CD8+effector memory re-expressing CD45RA (EMRA) T-cells and disruption of the kynurenine (KYN) pathway are associated with chronic inflammation and the development of insulin resistance.In this study the aim was to investigate the effects of 12-week combined strength and endurance exercise on CD8+T-cell differentiation and KYN pathway metabolites. Ninety-six elderly subjects (f/m, aged 50—70) were randomized to a control (CON) or exercise (EX) group. The EX group completed combined strength and endurance training twice weekly for one hour each time at an intensity of 60% of the one-repetition maximum for strength exercises and a perceived exertion of 15/20 for endurance exercises. The EX group was also randomly subdivided into two groups with or without a concomitant balanced diet intervention in order to examine additional effects besides exercise alone. Before and after the intervention phase, the proportions of CD8+T-cell subsets and levels of KYN pathway metabolites in peripheral blood were determined.ResultsThe CD8+EMRA T-cell subsets increased in the CON group but remained almost unchanged in the EX group (p = .02). Plasma levels of kynurenic acid (KA) increased in the EX group and decreased in the CON group (p = .03). Concomitant nutritional intervention resulted in lower levels of quinolinic acid (QA) compared with exercise alone (p = .03). Overall, there was a slight increase in the QA/KA ratio in the CON group, whereas it decreased in the EX group (p > .05).ConclusionsCombined strength and endurance training seems to be a suitable approach to attenuate CD8+T-cell differentiation in the elderly and to redirect the KYN pathway towards KA. The clinical relevance of these effects needs further investigation.
Serum E-selectin and endothelial cell-specific Molecule-1 levels among people living with HIV on long term ART in Uganda: a pilot cross-sectional study
Authors: Semulimi Andrew Weil , Batte Charles , Bayiyana Alice , Nakabuye Mariam , Mukisa John , Castelnuovo Barbara , Ratanshi Rosalind Parkes , Kirenga Bruce J , Ssinabulya Isaac 
Published: May 2023

Abstract
Background
Prolonged exposure to HIV and anti-retroviral therapy (ART) has been linked with endothelial cell activation which subsequently predisposes people living with HIV (PLWH) to cardiovascular diseases. Serum biomarkers of endothelial cell activation such as E-Selectin and endothelial cell-specific molecule-1 (ESM-1) could aid in early detection of PLWH at a risk of cardiovascular diseases. However, there is a paucity of data on these biomarkers like E-selectin and endothelial cell-specific molecule-1 (ESM-1) among PLWH on long term ART (≥ 10 years) in Uganda. The aim of this study is to determine the serum levels of these biomarkers in this population.

Methods
This was a cross-sectional study where we randomly sampled 73 stored serum samples of PLWH who were enrolled in the Infectious Diseases Institute (IDI) ART long term (ALT cohort). We measured serum levels of E-selectin and ESM-1 by ELISA. Data was summarized using median and interquartile range. Inferential statistics were performed to determine predictors of elevated levels of E-selectin.

Results
Of the 73 samples analyzed, 38 (52.1%) were from female participants. The mean age was 54 ± 9.0 years. Twenty participants (27.4%) had a history of smoking while 52 (71.2%) had a history of alcohol intake. Twenty-five (34.3%) of the participants were overweight whereas 4 (5.6%) were obese. Fifty-four (74%) had an undetectable viral load (≤ 0 copies/ml) and the mean duration of ART at the time of sampling (2014/2015) was 10.4 ± 0.4 years. While serum levels of ESM-1 were not detectable in any of our samples, the median E-selectin levels was 147.6 μm/L ranging from 8.44 μm/L and 1,979.36 μm/L. Sixty-seven participants (91.8%) had elevated levels of E-selectin (> 39 μm/L). CD4 count > 500 cells/µl compared to lower counts was a predictor of elevated levels of E-Selectin (adjusted Odd Ratio 12.5, 95% CI (1.03 — 149.95, p < 0.05).

Conclusions
The majority (91.8%) of PLWH on long term ART had elevated levels of E-selectin. Having high CD4 count (> 500 cells/µl) was predictive of elevated levels of E-Selectin. Future work should longitudinally assess the trend of levels of E-selectin and ESM-1 while assessing for cardiovascular diseases endpoint.
Cervical sagittal balance after consecutive three-level hybrid surgery versus anterior cervical discectomy and fusion: radiological results from a single-center experience
Authors: Chen Shihao , Deng Yuxiao , Liu Hao , Wu Tingkui , Huang Kangkang , He Junbo , Wang Beiyu 
Published: May 2023

Abstract
Introduction
According to the different numbers and relative locations of cervical disc replacement (CDR) and anterior cervical discectomy and fusion (ACDF), three-level hybrid surgery (HS) has many constructs. The purpose of this retrospective study was to compare the sagittal alignment parameters of HS and ACDF for cervical degenerative disc disease (CDDD) and the association of the respective parameters.

Methods
This study involved patients with three-level CDDD who underwent ACDF or HS at our institution between June 2012 and August 2021. This follow-up included one-level CDR and two-level ACDF (type I group), two-level CDR and one-level ACDF (type II group) and three-level ACDF. Cervical sagittal alignment parameters included cervical lordosis (CL), segment alignment (SA), T1 slope (T1S), C2–C7 sagittal vertical axis (SVA), T1S-CL, C2 slope (C2S), occipital to C2 angle (O-C2A) and segment range of motion (ROM). Postoperative complications included adjacent segment degeneration, imbalance, prosthetic subsidence and heterotopic ossification.

Results
The three groups with a total of 106 patients were better matched in terms of demographics. Patients who underwent HS had significantly higher CL than those who underwent ACDF at 1 week, 6 months, 12 months and the final follow-up after surgery, as well as significantly better SA at 12 months and the final follow-up. There was no significant difference in T1S, SVA, T1S-CL, C2S, O-C2A or segment ROM among the three groups after surgery. The T1S-CL was significantly associated with C2S in the type I and type II groups at the preoperative and final follow-up. There was no significant difference in postoperative complications among the three groups.

Conclusions
Most improvements in cervical sagittal alignment (CL, SA, T1S, SVA, T1S-CL, C2S, O-C2A, and segmental ROM) were observed in all three groups postoperatively. HS was more advantageous than ACDF in the maintenance of postoperative CL and SA. Thus, three-level HS may be better for maintaining cervical curvature. The number of replacement segments differed in those who underwent HS but did not affect the correlation between T1S-CL and C2S, both of which are well balanced.
Investigating significant health trends in growth hormone treatments registry: rationale, aims and design of a nationwide prospective registry (study protocol)
Authors: Schnabel Dirk , Kreitschmann-Andermahr Ilonka , Strasburger Christian J. , Pittrow David , Pausch Christine , Woelfle Joachim ,   for the INSIGHTS-GHT Study Group
Published: May 2023

Abstract
Background
Somatropin treatment is indicated in a variety of disorders including growth hormone (GH) deficiency, Prader–Willi and Turner syndrome, chronic renal insufficiency and others. To date, almost all studies have been limited to single GH products, and no independent registry across indications and somatropin products was ever established.

Aim
The present investigator-initiated registry named INSIGHTS-GHT aims to provide comprehensive information on various aspects of somatropin treatment in Germany in approved indications within routine clinical practice: drug utilization, effectiveness (including real final height, body composition), tolerability, quality of life, other patient related outcomes (PRO), and health economic variables.

Methods
Registry (prospective observational study) in specialised pediatric and adult endocrinology centres in Germany. Patients of any age are eligible for documentation, if they are on ongoing or newly initiated treatment with any approved somatropin or somatropin-related product within the labelling, available for long term follow-up documentation, and if they provided informed consent. Subjects may switch, discontinue/interrupt or initiate somatropin products at any time. They are followed up for at least 3 years (minimal study duration). Documentation is planned once or twice per year to record somatropin utilisation (product, dosing), other medications, laboratory status (glucose, lipids, GH function including stimulation tests, IGF-I, IGFBP3), if applicable, pubertal development, auxological parameters, body composition and bone age. Patient reported outcome (PRO) measures include, but are not limited to, Short Form 12 in adults and adolescents aged 14 years and over. Safety reporting includes adverse events.

Conclusions
The registry documents children and adults in one joint registry, includes, at present, patients in Germany and allows documentation of patients on all approved somatropin and other growth hormone preparations. It will allow to describe the transition of subjects from adolescence to adulthood (treatment and height), to describe switches between somatotropin preparations, to perform responder analyses, and to analyse differences and similarities of somatropin utilization (by age group, sex, setting, and PRO instrument). INSIGHTS-GHT offers a broad, comprehensive research platform to assess multiple relevant aspects of somatropin treatment and outcomes (including the transition of subjects from adolescence to adulthood), allows the documentation of all GH products including long-acting GH preparations after their introduction, and will evaluate the data independently of funders.
Trial registration BfArM Nr. NIS7492, DRKS registry DRKS00027394.
Secure attachment predicts lower societal cost amongst severely antisocial adolescents
Authors: Bachmann Christian J , Humayun Sajid , Stevens Madeleine , O’Connor Thomas G , Scott Stephen 
Published: May 2023

Abstract
Background
Social and economic costs associated with antisocial behaviour are well-established, but little is known about the potential costs savings/benefits of secure attachment in this high-risk group. We aimed to provide the first test of attachment quality as a distinct predictor of economic costs.

Methods
111 adolescents (10–17 years of age, M = 15.0, SD = 1.6; 71% male) referred to young offender services due to high levels of antisocial behaviour were included. Costs were measured by detailed service-use interview, and attachment security to mother and father elicited through the Child Attachment Interview. The level of antisocial behaviour and callous-unemotional traits were assessed. Cost predictors were calculated using generalised linear models.

Results
Mean 12-months service costs were £5,368 (sd 5,769) per adolescent, with justice system and educational service costs being the main components. After adjusting for covariates, economic costs were predicted by attachment quality to fathers, with a difference of £2,655 per year between those with secure (£3,338) versus insecure attachment (£5,993); significant cost effects were not found for attachment quality to mothers. Higher levels of callous-unemotional traits, lower verbal IQ, higher levels of antisocial behaviour, and older age were also significant cost predictors.

Conclusions
Secure attachment to fathers is a predictor of reduced public cost in adolescents with severe antisocial behaviour. This novel finding for severely antisocial youth extends previous findings in less antisocial children and underscores the public health and policy benefits of good caregiving quality and the value of population-level dissemination of evidence-based interventions that improve caregiving quality.
Expression of L1 retrotransposons in granulocytes from patients with active systemic lupus erythematosus
Authors: Ukadike Kennedy C. , Najjar Rayan , Ni Kathryn , Laine Amanda , Wang Xiaoxing , Bays Alison , Taylor Martin S. , LaCava John , Mustelin Tomas 
Published: May 2023

Abstract
Background
Patients with systemic lupus erythematosus (SLE) have autoantibodies against the L1-encoded open-reading frame 1 protein (ORF1p). Here, we report (i) which immune cells ORF1p emanates from, (ii) which L1 loci are transcriptionally active, (iii) whether the cells express L1-dependent interferon and interferon-stimulated genes, and (iv) the effect of inhibition of L1 ORF2p by reverse transcriptase inhibitors.

Results
L1 ORF1p was detected by flow cytometry primarily in SLE CD66b+CD15+ regular and low-density granulocytes, but much less in other immune cell lineages. The amount of ORF1p was higher in neutrophils from patients with SLE disease activity index (SLEDAI) > 6 (p = 0.011) compared to patients with inactive disease, SLEDAI < 4. Patient neutrophils transcribed seven to twelve human-specific L1 loci (L1Hs), but only 3 that are full-length and with an intact ORF1. Besides serving as a source of detectable ORF1p, the most abundant transcript encoded a truncated ORF2p reverse transcriptase predicted to remain cytosolic, while the two other encoded an intact full-length ORF2p. A number of genes encoding proteins that influence L1 transcription positively or negatively were altered in patients, particularly those with active disease, compared to healthy controls. Components of nucleic acid sensing and interferon induction were also altered. SLE neutrophils also expressed type I interferon-inducible genes and interferon β, which were substantially reduced after treatment of the cells with drugs known to inhibit ORF2p reverse transcriptase activity.

Conclusions
We identified L1Hs loci that are transcriptionally active in SLE neutrophils, and a reduction in the epigenetic silencing mechanisms that normally counteract L1 transcription. SLE neutrophils contained L1-encoded ORF1p protein, as well as activation of the type I interferon system, which was inhibited by treatment with reverse transcriptase inhibitors. Our findings will enable a deeper analysis of L1 dysregulation and its potential role in SLE pathogenesis.