bluuebunny/crossref_metadata_2025_split huggingface dataset:
Myocardial contrast echocardiography assessment of perfusion abnormalities in hypertrophic cardiomyopathy
Authors: Roldan Paola , Ravi Sriram , Hodovan James , Belcik J. Todd , Heitner Stephen B. , Masri Ahmad , Lindner Jonathan R. 
Published: September 2022

Abstract
Background
Perfusion defects during stress can occur in hypertrophic cardiomyopathy (HCM) from either structural or functional abnormalities of the coronary microcirculation. In this study, vasodilator stress myocardial contrast echocardiography (MCE) was used to quantify and spatially characterize hyperemic myocardial blood flow (MBF) deficits in HCM.

Methods
Regadenoson stress MCE was performed in patients with septal-variant HCM (n = 17) and healthy control subjects (n = 15). The presence and spatial distribution (transmural diffuse, patchy, subendocardial) of perfusion defects was determined by semiquantitative analysis. Kinetic analysis of time-intensity data was used to quantify MBF, microvascular flux rate (β), and microvascular blood volume. In patients undergoing septal myectomy (n = 3), MCE was repeated > 1 years after surgery.

Results
In HCM subjects, perfusion defects during stress occurred in the septum in 80%, and in non-hypertrophied regions in 40%. The majority of septal defects (83%) were patchy or subendocardial, while 67% of non-hypertrophied defects were transmural and diffuse. On quantitative analysis, hyperemic MBF was approximately 50% lower (p < 0.001) in the hypertrophied and non-hypertrophied regions of those with HCM compared to controls, largely based on an inability to augment β, although hypertrophic regions also had blood volume deficits. There was no correlation between hyperemic MBF and either percent fibrosis on magnetic resonance imaging or outflow gradient, yet those with higher degrees of fibrosis (≥ 5%) or severe gradients all had low septal MBF during regadenoson. Substantial improvement in hyperemic MBF was observed in two of the three subjects undergoing myectomy, both of whom had severe pre-surgical outflow gradients at rest.

Conclusion
Perfusion defects on vasodilator MCE are common in HCM, particularly in those with extensive fibrosis, but have a different spatial pattern for the hypertrophied and non-hypertrophied segments, likely reflecting different contributions of functional and structural abnormalities. Improvement in hyperemic perfusion is possible in those undergoing septal myectomy to relieve obstruction.

Trial registration
ClinicalTrials.gov NCT02560467.

Graphical Abstract
The glycocalyx affects the mechanotransductive perception of the topographical microenvironment
Authors: Chighizola Matteo , Dini Tania , Marcotti Stefania , D’Urso Mirko , Piazzoni Claudio , Borghi Francesca , Previdi Anita , Ceriani Laura , Folliero Claudia , Stramer Brian , Lenardi Cristina , Milani Paolo , Podestà Alessandro , Schulte Carsten 
Published: September 2022

AbstractThe cell/microenvironment interface is the starting point of integrin-mediated mechanotransduction, but many details of mechanotransductive signal integration remain elusive due to the complexity of the involved (extra)cellular structures, such as the glycocalyx. We used nano-bio-interfaces reproducing the complex nanotopographical features of the extracellular matrix to analyse the glycocalyx impact on PC12 cell mechanosensing at the nanoscale (e.g., by force spectroscopy with functionalised probes). Our data demonstrates that the glycocalyx configuration affects spatio-temporal nanotopography-sensitive mechanotransductive events at the cell/microenvironment interface. Opposing effects of major glycocalyx removal were observed, when comparing flat and specific nanotopographical conditions. The excessive retrograde actin flow speed and force loading are strongly reduced on certain nanotopographies upon strong reduction of the native glycocalyx, while on the flat substrate we observe the opposite trend. Our results highlight the importance of the glycocalyx configuration in a molecular clutch force loading-dependent cellular mechanism for mechanosensing of microenvironmental nanotopographical features.
Graphical Abstract
Cartilage targeting therapy with reactive oxygen species-responsive nanocarrier for osteoarthritis
Authors: Jiang Zengxin , Wang Hao , Zhang Zeng , Pan Jianfeng , Yuan Hengfeng 
Published: September 2022

AbstractTargeting cartilage is a promising strategy for the treatment of osteoarthritis, and various delivery vehicles were developed to assist the therapeutic agents into cartilage. However, the underlying biomechanisms and potential bioactivities remain oversimplified. Inspired by oxidative stress in the pathogenesis of osteoarthritis, we firstly testified the antioxidant capacity of a synthetic small molecule compound, oltipraz (OL), to the chondrocytes treated by IL-1β. Then a functional reactive oxygen species (ROS) responsive nanocarrier, mesoporous silica nanoparticles (MSN) modified with methoxy polyethylene glycol-thioketal, was constructed. In vitro biomolecular results showed that compared with OL alone, MSN-OL could significantly activate Nrf2/HO-1 signaling pathway, which exhibited better ROS-scavenging proficiency and greater anti-apoptotic ability to protect mitochondrial membrane potential of chondrocytes. Further bioinformatics analysis revealed that MSN-OL suppressed clusters of genes associated with extracellular matrix organization, cell apoptosis and cellular response to oxidative stress. Animal experiments further confirmed the great cartilage-protecting ability of MSN-OL through upregulating the expression of Nrf2/HO-1 signaling pathway without obvious toxicity. In summary, this study provided a delivery system through ROS-responsive regulation of the therapeutic agents into chondrocytes of the cartilage, and confirmed the exact biological mechanisms of this innovative strategy.
The prognostic impact of lead times in colorectal cancer patients undergoing cytoreductive surgery and HIPEC
Authors: Jansson Ylva , Graf Wilhelm , Ghanipour Lana 
Published: September 2022

Abstract
Background
National lead time goals have been implemented across Sweden to standardize and improve cancer patient care. However, the prognostic impact of lead times has not yet been studied in patients with colorectal cancer and peritoneal metastases scheduled for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS + HIPEC).

Aim
To study the correlation between lead times and overall survival and operability.

Methods
One hundred forty-eight patients with peritoneal metastases originating from colorectal cancer and scheduled for CRS + HIPEC from June 2012 to December 2019 were identified using a HIPEC register at Uppsala University Hospital. Data were collected from medical records concerning operability, overall survival, recurrence and time from diagnosis, and decision to operate to the date of surgery. Patients who had neoadjuvant therapy or no malignant cells in the resected specimens were excluded. Statistical calculations were made with the chi-squared test, Cox regression analysis, and log-rank test.

Results
The median age was 66 years (27–82). Ninety-five were women and 53 were men. One hundred six underwent CRS + HIPEC, 13 CRS only, and 29 were inoperable (open-close). No difference in overall survival was seen when comparing patients with lead times ≤ 34 days and ≥ 35 days from the decision to operate at the multidisciplinary conference to the surgery but there was a higher frequency of open-close (p = 0.023) in the group with longer lead time. Factors that impacted overall survival were open-close (p < 0.001), liver metastases (p = 0.003), and peritoneal cancer index score ≥ 20 (p < 0.001).

Conclusion
A long lead time from multidisciplinary conference to surgery has no direct impact on overall survival but can result in more cases of inoperability. In a larger cohort, this might translate into decreased survival, and efforts should therefore be made to complete preoperative work up as soon as possible and reduce overall time span. Important factors for survival are related to patient selection and extent of disease.
The follicular-phase depot GnRH agonist protocol results in a higher live birth rate without discernible differences in luteal function and child health versus the daily mid-luteal GnRH agonist protocol: a single-centre, retrospective, propensity score matched cohort study
Authors: Zhang Ying , Zhao Wenxian , Han Yifan , Chen Xin , Xu Shaoyuan , Hu Yueyue , Diao Honglu , Zhang Changjun 
Published: September 2022

Abstract
Background
The gonadotropin-releasing hormone agonist (GnRH-a) has been used in in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles for a long time. This paper evaluates the efficacy and safety of two commonly used protocols (follicular-phase depot GnRH-a protocol and daily mid-luteal long GnRH-a protocol) in normal responders undergoing IVF/ICSI using propensity score matching (PSM) analysis.

Methods
A total of 6,816 infertile women treated within the period from January 2016 to September 2020 were stratified into cohorts. A total of 2,851 patients received the long-acting group (depot GnRH-a protocol), and 1,193 used the short-acting group (long GnRH-a protocol) after the data-selection process. PSM was utilized for sampling by up to 1:1 nearest neighbour matching to adjust the numerical difference and balance the confounders between groups. The primary outcome was the live birth rate (LBR). Multivariable logistic analysis was used to evaluate the difference between these two protocols in relation to the LBR.

Result(s)
In this study, 1:1 propensity score matching was performed to create a perfect match of 964 patients in each group. After matching, the blastocyst formation rates, oestradiol (E2) value on Day hCG + 9, progesterone (P) value on Day hCG + 9, implantation rates, clinical pregnancy rates, and LBR were more favourable in the depot GnRH-a protocol than in the long GnRH-a protocol (P < 0.05). However, the moderate or severe OHSS rates were higher in the depot group than in the long group (P < 0.001). There were no significant differences in endometrial thickness, luteal support medication, early pregnancy loss rates, mid- and late-term pregnancy loss rates, or foetal malformation rates between the two protocols.

Conclusion(s)
Compared with the daily short-acting GnRH agonist protocol, the follicular-phase depot GnRH-a protocol might improve LBRs in normogonadotropic women without discernible differences in luteal function and child health.
Review of potential medical treatments for middle ear cholesteatoma
Authors: Schürmann Matthias , Goon Peter , Sudhoff Holger 
Published: September 2022

AbstractMiddle ear cholesteatoma (MEC), is a destructive, and locally invasive lesion in the middle ear driven by inflammation with an annual incidence of 10 per 100,000. Surgical extraction/excision remains the only treatment strategy available and recurrence is high (up to 40%), therefore developing the first pharmaceutical treatments for MEC is desperately required. This review was targeted at connecting the dysregulated inflammatory network of MEC to pathogenesis and identification of pharmaceutical targets. We summarized the numerous basic research endeavors undertaken over the last 30+ years to identify the key targets in the dysregulated inflammatory pathways and judged the level of evidence for a given target if it was generated by in vitro, in vivo or clinical experiments. MEC pathogenesis was found to be connected to cytokines characteristic for Th1, Th17 and M1 cells. In addition, we found that the inflammation created damage associated molecular patterns (DAMPs), which further promoted inflammation. Similar positive feedback loops have already been described for other Th1/Th17 driven inflammatory diseases (arthritis, Crohn’s disease or multiple sclerosis). A wide-ranging search for molecular targeted therapies (MTT) led to the discovery of over a hundred clinically approved drugs already applied in precision medicine. Based on exclusion criteria designed to enable fast translation as well as efficacy, we condensed the numerous MTTs down to 13 top drugs. The review should serve as groundwork for the primary goal, which is to provide potential pharmaceutical therapies to MEC patients for the first time in history.
A review on exosomes application in clinical trials: perspective, questions, and challenges
Authors: Rezaie Jafar , Feghhi Maryam , Etemadi Tahereh 
Published: September 2022

AbstractBackgroundExosomes are progressively known as significant mediators of cell-to-cell communication. They convey active biomolecules to target cells and have vital functions in several physiological and pathological processes, and show substantial promise as novel treatment strategies for diseases.MethodsIn this review study, we studied numerous articles over the past two decades published on application of exosomes in different diseases as well as on perspective and challenges in this field.ResultsThe main clinical application of exosomes are using them as a biomarker, cell-free therapeutic agents, drug delivery carriers, basic analysis for exosome kinetics, and cancer vaccine. Different exosomes from human or plant sources are utilized in various clinical trials. Most researchers used exosomes from the circulatory system for biomarker experiments. Mesenchymal stem cells (MSCs) and dendritic cells (DCs) are two widely held cell sources for exosome use. MSCs-derived exosomes are commonly used for inflammation treatment and drug delivery, while DCs-exosomes are used to induce inflammation response in cancer patients. However, the clinical application of exosomes faces various questions and challenges. In addition, translation of exosome-based clinical trials is required to conform to specific good manufacturing practices (GMP). In this review, we summarize exosomes in the clinical trials according to the type of application and disease. We also address the main questions and challenges regarding exosome kinetics and clinical applications.ConclusionsExosomes are promising platforms for treatment of many diseases in clinical trials. This exciting field is developing hastily, understanding of the underlying mechanisms that direct the various observed roles of exosomes remains far from complete and needs further multidisciplinary research in working with these small vesicles.
Prevalence and risk factors of high cholesterol and triglycerides among people with HIV in Texas
Authors: Buendia Justin , Sears Sabeena , Mgbere Osaro 
Published: September 2022

Abstract
Background
People with HIV (PWH) commonly have elevated cholesterol and triglycerides levels that have been linked to medications. However, healthy behaviors including lifestyle changes can lower high cholesterol (CHOL) or high triglycerides (TG), thereby reducing individual risk for cardiovascular diseases. This study aimed to determine the prevalence and risk factors associated with high CHOL or TG among PWH in Texas.

Methods
Cross-sectional data of 981 PWH from the 2015–2017 Texas and Houston Medical Monitoring Projects were examined. High CHOL or TG was identified by medical chart diagnosis, CHOL or TG medication use, or most recent fasting lab ≥ 200 mg/dl (total CHOL) or ≥ 150 mg/dl (TG). High CHOL or TG associations with sociodemographic and clinical characteristics were assessed using Rao-Scott chi-square tests. Prevalence of high CHOL or TG development was calculated using multivariable logistic regression model.

Results
High CHOL or TG prevalence was 41% with participants being mostly male (73%), ≥ 40 years (68%), with overweight (31%) or obesity (28%), and virally suppressed (62%). Compared with PWH < 40 years of age, PWH in their 40s, 50s, and ≥ 60s were 57%, 64%, and 62% more likely to have high CHOL or TG, respectively. Participants with overweight and obesity were 41% and 30% more likely to have high CHOL or TG than those with normal weight (BMI: 18.5– < 25), respectively.

Conclusion
Since high CHOL and TG are modifiable CVD risk factors, increased education and lifestyle modification interventions are warranted to prevent the development of high CHOL or TG among PWH.
BK and JC polyomaviruses and risk of urothelial bladder carcinoma: a preliminary study in the northern shores of Persian Gulf, Iran
Authors: Taherkhani Reza , Farshadpour Fatemeh 
Published: September 2022

Abstract
Background
Bladder cancer is a challenging public health concern in South of Iran because of its high prevalence and the related medical expenses. Although the exact etiology of bladder cancer remains unknown, given the cell transforming ability and oncogenic potential of the members of Polyomaviridae families, this study was conducted to evaluate the magnitude of BK polyomavirus (BKPyV) and John Cunningham polyomavirus (JCPyV) among patients with bladder cancer residents in the northern shores of the Persian Gulf, South of Iran.

Methods
Totally 211 patients with bladder cancer were enrolled in this study. Bladder biopsy samples of these patients and patients with interstitial cystitis as well as autoptic samples of healthy bladder were tested for detection of BKPyV and JCPyV by semi-nested PCR–RFLP followed by sequencing.

Results
BKPyV and JCPyV were detected in 1.7% and 6.1% of bladder cancer samples, respectively. These samples were infected with JCPyV genotypes 2, 3 and 6 and BKPyV genotypes I and IV. BKPyV and JCPyV coinfection was detected in 2 samples. Moreover, one of the healthy bladder samples was positive for BKPyV, and one of the interstitial cystitis samples was positive for JCPyV. Although the majority of infected patients were in the age group 70–79 years, male, residents in Tangestan, stage Ta–T1, and low-grade and high-grade papillary urothelial carcinoma, the prevalence of BKPyV and JCPyV among patients with bladder cancer was not statistically associated with age, gender, place of residency, and stage and grade of the tumor.

Conclusion
Despite identifying BKPyV and JCPyV in a number of bladder cancer biopsy specimens and the high prevalence of bladder cancer among people resident in South of Iran, it is suggested that these viruses are unlikely to be effective causative factors in bladder carcinogenesis in this region. Therefore, environmental risk factors and genetic backgrounds may have a more prominent role than human polyomaviruses in the development of bladder cancer in South of Iran.
Associations between perceived stress and health outcomes in adolescents
Authors: Thorsén Frida , Antonson Carl , Palmér Karolina , Berg Rada , Sundquist Jan , Sundquist Kristina 
Published: September 2022

AbstractBackgroundAdolescents are reporting increasing symptoms of anxiety, depression and somatization and an increase in perceived stress is a plausible explanation. The first aim of this study was to examine the occurrence of perceived stress and health outcomes in adolescents, and to evaluate if there are any sex differences. The second aim was to investigate if there is an association between perceived stress and the health outcomes and, if so, possible gender differences in this association. The third aim was to compare samples of adolescent girls and boys from two different European countries to enhance the generalizability of potential findings.MethodsThe sample included 636 students from Sweden and Bulgaria, aged 15–16, 164 (58% males, 41% females, 1% not specified) from Sweden and 472 (71% males, 28% females, 1% not specified) from Bulgaria. Perceived stress and health outcomes were measured by the 14-item “Perceived Stress Scale” (PSS-14), and a shorter version of the questionnaire "Children and Young People in Skåne" (Folkhälsoenkäten, FHE), respectively. T-test and Chi2and/or Fisher’s exact test was used to compare results between boys and girls from the PSS-14 and health outcomes. The association between PSS and the health outcomes was assessed using Spearman’s rank correlation and comparisons between boys and girls were calculated using linear regression.ResultsThere were significant associations between perceived stress and psychiatric symptoms in all groups. Adolescent girls in both Sweden and Bulgaria consistently reported higher levels of perceived stress and more psychiatric and somatic symptoms than the boys.ConclusionsEvaluating methods for lessening the perception of stress, and their clinical presentation, should be considered in order to reduce the occurrence of psychiatric symptoms in adolescents.
Repurposing of the Malaria Box for Babesia microti in mice identifies novel active scaffolds against piroplasmosis
Authors: Rizk Mohamed Abdo , Baghdadi Hanadi B. , El-Sayed Shimaa Abd El-Salam , Eltaysh Rasha , Igarashi Ikuo 
Published: September 2022

Abstract
Background
An innovative approach has been introduced for identifying and developing novel potent and safe anti-Babesia and anti-Theileria agents for the control of animal piroplasmosis. In the present study, we evaluated the inhibitory effects of Malaria Box (MBox) compounds (n = 8) against the growth of Babesia microti in mice and conducted bioinformatics analysis between the selected hits and the currently used antibabesial drugs, with far-reaching implications for potent combinations.

Methods
A fluorescence assay was used to evaluate the in vivo inhibitory effects of the selected compounds. Bioinformatics analysis was conducted using hierarchical clustering, distance matrix and molecular weight correlation, and PubChem fingerprint. The compounds with in vivo potential efficacy were selected to search for their target in the piroplasm parasites using quantitative PCR (qPCR).

Results
Screening the MBox against the in vivo growth of the B. microti parasite enabled the discovery of potent new antipiroplasm drugs, including MMV396693 and MMV665875. Interestingly, statistically significant (P < 0.05) downregulation of cysteine protease mRNA levels was observed in MMV665875-treated Theileria equi in vitro culture in comparison with untreated cultures. MMV396693/clofazimine and MMV665875/atovaquone (AV) showed maximum structural similarity (MSS) with each other. The distance matrix results indicate promising antibabesial efficacy of combination therapies consisting of either MMV665875 and AV or MMV396693 and imidocarb dipropionate (ID).

Conclusions
Inhibitory and hematology assay results suggest that MMV396693 and MMV665875 are potent antipiroplasm monotherapies. The structural similarity results indicate that MMV665875 and MMV396693 have a similar mode of action as AV and ID, respectively. Our findings demonstrated that MBox compounds provide a promising lead for the development of new antibabesial therapeutic alternatives.

Graphical Abstract