bluuebunny/crossref_metadata_2025 huggingface dataset:
Reporting of conflicts of interest by authors of primary studies on health policy and systems research: a cross-sectional survey
Authors: Hakoum Maram B , Bou-Karroum Lama , Al-Gibbawi Mounir , Khamis Assem M , Raslan Abdul Sattar , Badour Sanaa , Agarwal Arnav , Alturki Fadel , Guyatt Gordon , El-Jardali Fadi , Akl Elie A
Published: July 2020

Objectives

The objective of this study was to assess the frequency and types of conflict of interest (COI) disclosed by authors of primary studies of health policy and systems research (HPSR).

Design

We conducted a cross-sectional survey using standard systematic review methodology for study selection and data extraction. We conducted descriptive analyses.

Setting

We collected data from papers published in 2016 in ‘health policy and service journals’ category in Web of Science database.

Participants

We included primary studies (eg, randomised controlled trials, cohort studies, qualitative studies) of HPSR published in English in 2016 peer-reviewed health policy and services journals.

Outcome measures

Reported COI disclosures including whether authors reported COI or not, form in which COI disclosures were provided, number of authors per paper who report any type of COI, number of authors per paper who report specific types and subtypes of COI.

Results

We included 200 eligible primary studies of which 132 (66%) included COI disclosure statements of authors. Of the 132 studies, 19 (14%) had at least one author reporting at least one type of COI and the most frequently reported type was individual financial COI (n=15, 11%). None of the authors reported individual intellectual COIs or personal COIs. Financial and individual COIs were reported more frequently compared with non-financial and institutional COIs.

Conclusion

A low percentage of HPSR primary studies included authors reporting COI. Non-financial or institutional COIs were the least reported types of COI.
Randomised phase II trial of CAPTEM or FOLFIRI as SEcond-line therapy in NEuroendocrine CArcinomas and exploratory analysis of predictive role of PET/CT imaging and biological markers (SENECA trial): a study protocol
Authors: Bongiovanni Alberto , Liverani Chiara , Pusceddu Sara , Leo Silvana , Di Meglio Giovanni , Tamberi Stefano , Santini Daniele , Gelsomino Fabio , Pucci Francesca , Berardi Rossana , Lolli Ivan , Bergamo Francesca , Ricci Sergio , Foca Flavia , Severi Stefano , Ibrahim Toni
Published: July 2020

Introduction

Patients with metastatic or locally advanced, non-resectable, grade 3 poorly differentiated gastroenteropancreatic (GEP) and lung neuroendocrine carcinomas (NECs) are usually treated with in first-line platinum compounds. There is no standard second-line treatment on progression. Accurate biomarkers are needed to facilitate diagnosis and prognostic assessment of patients with NEC.

Methods and analysis

The SEcond-line therapy in NEuroendocrine CArcinomas (SENECA) study is a randomised, non-comparative, multicentre phase II trial designed to evaluate the efficacy and safety of folinic acid, 5-fluorouracil and irinotecan (FOLFIRI) or capecitabine plus temozolomide (CAPTEM) regimens after failure of first-line chemotherapy in patients with lung NEC and GEP-NEC. Secondary aims are to correlate the serum miRNA profile and primary mutational status of MEN1, DAXX, ATRX and RB-1 with prognosis and outcome and to investigate the prognostic and predictive role of the Ki-67 score and 18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) or 68Ga-PET/CT. The main eligibility criteria are age ≥18 years; metastatic or locally advanced, non-resectable, grade 3 lung or GEP-NECs; progression to first-line platinum-based chemotherapy. A Bryant and Day design taking into account treatment activity and toxicity was used to estimate the sample size. All analyses will be performed separately for each treatment group in the intention-to-treat population. A total of 112 patients (56/arm) will be randomly assigned (1:1) to receive FOLFIRI every 14 days or CAPTEM every 28 days until disease progression or unacceptable toxicity or for a maximum of 6 months. Patients undergo testing for specific biomarkers in primary tumour tissue and for miRNA in blood samples. MiRNA profiling will be performed in the first 20 patients who agree to participate in the biological substudy.

Ethics and dissemination

The SENECA trial, supported by Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST), was authorised by the locals Ethics Committee and the Italian Medicines Agency (AIFA). Results will be widely disseminated via peer-reviewed manuscripts, conference presentations and reports to relevant authorities.

The study is currently open in Italy.

Trail registration number

NCT03387592; Pre-results. EudraCT-2016-000767-17.

Protocol version

Clinical Study Protocol Version 1, 7 November 2016.
‘Our culture prohibits some things’: qualitative inquiry into how sociocultural context influences the scale-up of community-based injectable contraceptives in Nigeria
Authors: Akinyemi Oluwaseun Oladapo , Harris Bronwyn , Kawonga Mary
Published: July 2020

Objectives

To explore how sociocultural factors may support or impede the adoption of community-based distribution of injectable contraceptives in Nigeria.

Design

A qualitative study based on inductive thematic analysis was conducted through in-depth interviews and focus group discussions.

Setting

Most participants lived in Gombe State, North-East Nigeria. Other participants were from Ibadan (South-West) and Abuja (Federal Capital Territory).

Participants

Through seven key informant interviews, 15 in-depth interviews and 10 focus group discussions, 102 participants were involved in the study.

Methods

This study conducted in 2016 was part of a larger study on scale-up of community-based distribution of injectable contraceptives. Qualitative data were collected from traditional and religious leaders, health workers and community members. The data were audio recorded, transcribed and analysed using a thematic framework method.

Results

Sociocultural challenges to scale-up included patriarchy and men’s fear of losing control over their spouses, traditional and religious beliefs about fertility, and myths about contraceptives and family planning. As a result of deep-rooted beliefs that children are ‘divine blessings’ and that procreation should not be regulated, participants described a subtle resistance to uptake of injectable contraceptives. Since Gombe is largely a patriarchal society, male involvement emerged as important to the success of meaningful innovation uptake. Community leaders largely described their participation in the scale-up process as active, although they also identified the scope for further involvement and recognition.

Conclusion

Scale-up is more than setting up health sector implementing structures, training health workers and getting innovation supplies, but also requires preparedness which includes paying attention to complex contextual issues. Policy implementers should also see scale-up as a learning process and be willing to move at the speed of the community.
Cohort profile: Center for Research on Early Childhood Exposure and Development in Puerto Rico
Authors: Manjourides Justin , Zimmerman Emily , Watkins Deborah J , Carpenito Thomas , Vélez-Vega Carmen M , Huerta-Montañez Gredia , Rosario Zaira , Ayala Ishwara , Vergara Carlos , Feric Zlatan , Ondras Martha , Suh Helen H , Gu April Z , Brown Phil , Cordero José F , Meeker John D , Alshawabkeh Akram
Published: July 2020

Purpose

Puerto Rican children experience high rates of asthma and obesity. Further, infants born in Puerto Rico are more at risk for being born prematurely compared with infants on the mainland USA. Environmental exposures from multiple sources during critical periods of child development, potentially modified by psychosocial factors, may contribute to these adverse health outcomes. To date, most studies investigating the health effects of environmental factors on infant and child health have focused on single or individual exposures.

Participants

Infants currently in gestation whose mother is enrolled in Puerto Rico Testsite for Exploring Contamination Threats (PROTECT) cohort, and infants and children already born to mothers who participated in the PROTECT study.

Findings to date

Data collection and processing remains ongoing. Demographic data have been collected on 437 mother–child pairs. Birth outcomes are available for 420 infants, neurodevelopmental outcomes have been collected on 319 children. Concentrations of parabens and phenols in maternal spot urine samples have been measured from 386 mothers. Center for Research on Early Childhood Exposure and Development mothers have significantly higher urinary concentrations of dichlorophenols, triclosan and triclocarban, but lower levels of several parabens compared with reference values from a similar population drawn from the National Health and Nutrition Examination Survey.

Future plans

Data will continue to be collected through recruitment of new births with a target of 600 children. Seven scheduled follow-up visits with existing and new participants are planned. Further, our research team continues to work with healthcare providers, paediatricians and early intervention providers to support parent’s ability to access early intervention services for participants.
Imputing HbA1c from capillary blood glucose levels in patients with type 2 diabetes in Sri Lanka: a cross-sectional study
Authors: Choo Monica , Hoy Gregory E. , Dugan Sarah P. , McEwen Laura N. , Gunaratnam Naresh , Wyckoff Jennifer , Jeevaraaj Thangarasa , Saththiyaseelan Arunachalam , Ganeikabahu B. , Katulanda Prasad , Balis Ulysses , Herman William H. , Saha Anjan K.
Published: July 2020

Objective

To develop a population-specific methodology for estimating glycaemic control that optimises resource allocation for patients with diabetes in rural Sri Lanka.

Design

Cross-sectional study.

Setting

Trincomalee, Sri Lanka.

Participants

Patients with non-insulin-treated type 2 diabetes (n=220) from three hospitals in Trincomalee, Sri Lanka.

Outcome measure

Cross-validation was used to build and validate linear regression models to identify predictors of haemoglobin A1c (HbA1c). Validation of models that regress HbA1c on known determinants of glycaemic control was thus the major outcome. These models were then used to devise an algorithm for categorising the patients based on estimated levels of glycaemic control.

Results

Time since last oral intake other than water and capillary blood glucose were the statistically significant predictors of HbA1c and thus included in the final models. In order to minimise type II error (misclassifying a high-risk individual as low-risk or moderate-risk), an algorithm for interpreting estimated glycaemic control was created. With this algorithm, 97.2% of the diabetic patients with HbA1c ≥9.0% were correctly identified.

Conclusions

Our calibrated algorithm represents a highly sensitive approach for detecting patients with high-risk diabetes while optimising the allocation of HbA1c testing. Implementation of these methods will optimise the usage of resources devoted to the management of diabetes in Trincomalee, Sri Lanka. Further external validation with diverse patient populations is required before applying our algorithm more widely.
Anticholinergic medications even in therapeutic range can cause recurrence of psychosis
Authors: Das Soumitra , Chatterjee Seshadri Sekhar , Malathesh Barikar Chandrappa
Published: July 2020

Anticholinergic drugs are commonly used in psychiatry to attenuate antipsychotic induced extrapyramidal syndrome (EPS). Psychosis as a side effect is generally explained under the rubric of anticholinergic toxicity or induced delirium. Anticholinergic induced worsening of psychosis in patients with normal cognition is extremely rare in literature. Here, we arepresenting a case of young female who was prescribed with multiple anticholinergics to reduce EPS, and each time had worsening of psychosis with intact cognition. We then discussed the possible neurobiological explanation with special reference to muscarinic hypothesis of schizophrenia.
Eisenmenger syndrome: diagnosis, prognosis and clinical management
Authors: Arvanitaki Alexandra , Giannakoulas George , Baumgartner Helmut , Lammers Astrid Elisabeth
Published: July 2020

Eisenmenger syndrome (ES) represents the most severe phenotype of pulmonary arterial hypertension (PAH) associated with congenital heart disease (CHD) and occurs in patients with large unrepaired shunts. Despite early detection of CHD and major advances in paediatric cardiac surgery, ES is still prevalent and requires a multidisciplinary approach by adult CHD experts in tertiary centres. Central cyanosis is the primary clinical manifestation leading to secondary erythrocytosis and various multiorgan complications that increase morbidity and affect quality of life. Close follow-up is needed to early diagnose and timely manage these complications. The primary goal of care is to maintain patients’ fragile stability. Although the recent use of advanced PAH therapies has substantially improved functional capacity and increased life expectancy, long-term survival remains poor. Progressive heart failure, infectious diseases and sudden cardiac death comprise the main causes of death in patients with ES. Impaired exercise tolerance, decreased arterial oxygen saturation, iron deficiency, pre-tricuspid shunts, arrhythmias, increased brain natriuretic peptide, echocardiographic indices of right ventricular dysfunction and hospitalisation for heart failure predict mortality. Endothelin receptor antagonists are used as first-line treatment in symptomatic patients, while phosphodiesterase-5 inhibitors may be added. Due to the lack of evidence, current guidelines do not provide a clear therapeutic strategy regarding treatment escalation. Additional well-designed trials are required to assess the comparative efficacy of various PAH agents and the benefit of combination therapy. Finally, the development of a risk score is of utmost importance to guide clinical therapy.
Mir-30B-5P Inhibits Proliferation and Promotes Apoptosis of Medulloblastoma Cells via Targeting Myb Proto-Oncogene like 2 (Mybl2)
Authors: Xu Chengyan , He Zixia , Lin Chao , Shen Zhipeng
Published: July 2020

Medulloblastoma (MB) is the most common malignant brain tumors among children. MiR-30b-5p is a potential tumor suppressor in a variety of human cancers. However, its expression and function in MB remain poorly understood. This study aimed to investigate the expression, role and regulatory mechanism of miR-30b-5p in MB. The expression of miR-30b-5p in MB tissues and cell lines was detected by real-time PCR. The effects of miR-30b-5p on cell proliferation and apoptosis were monitored by CCK-8 (Cell Counting Kit-8) assay, colony formation assay and flow cytometry, respectively. Bioinformatics database TargetScan predicted the target genes of miR-30b-5p. The interaction between miR-30b-5p and MYB proto-oncogene Like 2 (MYBL2) was determined by luciferase reporter gene assay. We demonstrated that the expression of miR-30b-5p was significantly downregulated in MB. Upregulated miR-30b-5p could inhibit the proliferation and induce apoptosis of MB.

Moreover, overexpressed miR-30b-5p could increase the expression of BAX but decrease that of Bcl-2. Downregulated miR-30b-5p exerted the opposite effect. MYBL2 was proved to be the target gene of miR-30b-5p and was negatively regulated by miR-30b-5p. These results indicate that miR-30b-5p inhibits the progression of MB via targeting the expression of MYBL2.
Status of SARS-CoV-2 in cerebrospinal fluid of patients with COVID-19 and stroke
Authors: Al Saiegh Fadi , Ghosh Ritam , Leibold Adam , Avery Michael B , Schmidt Richard F , Theofanis Thana , Mouchtouris Nikolaos , Philipp Lucas , Peiper Stephen C , Wang Zi-Xuan , Rincon Fred , Tjoumakaris Stavropoula I , Jabbour Pascal , Rosenwasser Robert H , Gooch M. Reid
Published: July 2020

Background

Emergence of the novel corona virus (severe acute respiratory syndrome (SARS)-CoV-2) in December 2019 has led to the COVID-19 pandemic. The extent of COVID-19 involvement in the central nervous system is not well established, and the presence or the absence of SARS-CoV-2 particles in the cerebrospinal fluid (CSF) is a topic of debate.

Case description

We present two patients with COVID-19 and concurrent neurological symptoms. Our first patient is a 31-year-old man who had flu-like symptoms due to COVID-19 and later developed an acute-onset severe headache and loss of consciousness and was diagnosed with a Hunt and Hess grade 3 subarachnoid haemorrhage from a ruptured aneurysm. Our second patient is a 62-year-old woman who had an ischaemic stroke with massive haemorrhagic conversion requiring a decompressive hemicraniectomy. Both patients’ CSF was repeatedly negative on real-time PCR analysis despite concurrent neurological disease.

Conclusion

Our report shows that patients’ CSF may be devoid of viral particles even when they test positive for COVID-19 on a nasal swab. Whether SARS-CoV-2 is present in CSF may depend on the systemic disease severity and the degree of the virus’ nervous tissue tropism and should be examined in future studies.
3 The dopaminergic balancing act: a literature review of a novel COMT inhibitor opicapone with a focus on the risk of visual hallucinations
Authors: Cole Richard , Saha Romi
Published: July 2020

Aims

Parkinson’s Disease (PD) medications are well-evidenced for improving motor symptoms. However, often a balancing act is required to ameliorate positive neuropsychiatric symptoms, such as visual hallucinations (VH). Opicapone, a novel COMT inhibitor, has been shown by BIPARK-1 and BIPARK-2 studies to improve wearing-off phenomena but little is known about associated neuropsychiatric symptoms. The aim of this literature review was to investigate any association between opicapone and VH.

Methods

A literature review was undertaken on the 18th July 2019 using PubMed, Ovid (using key resources of Embase, Ovid MEDLINE, Global Health and PsycINFO), Web of Science and Scopus. The search terms used were ‘Parkinson’s Disease’ and ‘Opicapone’. The search included full-texts, abstracts, conference abstracts and posters.

Results

The initial search produced 398 articles; 391 were excluded. Of the 7 articles reviewed there were two randomised controlled trials (RCTs) (BIPARK-1 and -2), two observational studies, two post-hoc analyses of BIPARK-1 and -2, and one retrospective analysis. BIPARK-1 reported VH in 1% of the entacapone group, 8% opicapone 25 mg group and 4% of the opicapone 50 mg group. BIPARK-2 did not report on VH in their randomised phased and reported VH in 0.8% of opicapone patients in their open-label phase but without specifying the associated dose.

Chaudhuri et al.’s (2018) post-hoc analysis of BIPARK-1 reported VH in 8% of COMT- naive patients given opicapone, vs. 1% of those given entacapone. Lees et al.’s (2019) post-hoc analysis of BIPARK-1 & -2 reported VH in 4.6% of patients receiving opicapone who were ≥70 years old, vs 0.6% in those younger. Gandor et al.’s (2018) prospective observational study reported VH in 14.8% of patients given opicapone.

Conclusions

Several factors limit the conclusions drawn about the risk of VH in patients taking opicapone. The RCTs were designed and powered to assess ‘on-off’ phenomena and didn’t include patients >65 or with a psychiatric history. This also limits their post-hoc analyses’ generalisability. The more ‘real-world’ observational studies were small and only available in abstract form with limited details. Lees et al.’s (2019) post-hoc analysis nevertheless reported a higher incidence of VH in the older age group, which is concordant with known risk factors for neuropsychiatric adverse events. Further investigation is required, focusing on older patients and those with a psychiatric history or cognitive impairment.
8 Functional neurological disorder (FND) patients’ experience of healthcare interventions
Authors: Symeon C , Isaacs-Itua A , Saramandi A
Published: July 2020

Objectives

Despite Functional Neurological Disorder (FND) accounting for approximately 25% of Neurology out-patient appointments, and being frequently comorbid with other neurological conditions, there are only 4 centres in the UK, offering in-patient treatment programmes. Subsequently, services are strained as patients face long waiting lists and likely deterioration of symptoms. We explored patients’ experience of this and the impact on their wellbeing.

Methods

An on-line survey was sent to patients with a diagnosis of FND, who had, at out- patient assessment been deemed appropriate candidates for in-patient rehabilitation, and had provided written consent to be included in research. The survey question themes included: demography, understanding of FND diagnosis, subjective opinion of symptom progression, use of primary care services and/or Emergency Departments, and access to support and employment opportunities.

Response where subjective opinion was sought, e.g. understanding of diagnosis, was via Likert scale ratings (from 0 (no understanding at all) to 10 (full understanding). All responses were anonymous.

Results

12 patients completed the survey (n=12). Of these, 7 were female and 5, male. 11 patients were aged between 25–64 years and 1, aged over 65 years. More than half of patients had seen their GP or visited an Emergency Department with symptoms related to FND in the past year. Average understanding of FND diagnosis was rated as 6.5, of treatment options as 4.8 and confidence of the likelihood of full recovery as 3.5 (on a scale of 0–10). 7 patients had carers, of whom the majority were family members. 9 patients would consider the use of digital interventions or day therapy programmes and 10 patients had already completed an in-patient rehabilitation programme. Of these, 9 had been on the in-patient waiting list for over 6 months. 8 patients felt that their symptoms had deteriorated and 6 patients described their level of independence, as being ‘much worse’, while on the waiting list.

Conclusions

While we appreciate that this is a small sample size, it does offer invaluable insight into the experiences of those with FND, particularly with regards to healthcare intervention. Patients with FND inevitably use what would be regarded as high levels of healthcare intervention, although this must be considered within the context of limited healthcare resources available to them.
Heart team approach in treatment of mitral regurgitation: patient selection and outcome
Authors: Külling Mischa , Corti Roberto , Noll Georg , Küest Silke , Hürlimann David , Wyss Christophe , Reho Ivano , Tanner Felix C , Külling Jeremy , Meinshausen Nicolai , Gaemperli Oliver , Wenaweser Peter , Salzberg Sacha P , Aymard Thierry , Grünenfelder Jürg , Biaggi Patric
Published: July 2020

Objective

A multidisciplinary heart valve team is recommended for the evaluation of treatment in patients with valvular heart disease, but evidence supporting this concept is lacking. In patients with severe mitral regurgitation, we thought to analyse the patient selection process by the heart team for different treatment options and the outcome after treatment.

Methods

In this single-centre cohort study, all patients treated for mitral regurgitation between July 2013 and September 2018 were included. Primary end points during follow-up were all-cause mortality and a combined end point, consisting of all-cause mortality, cardiovascular rehospitalisation and mitral valve reintervention.

Results

179 patients (44.8%) were treated using Mitraclip, 185 (46.2%) by surgical repair and 36 (9.0%) by surgical replacement. The mortality risk according to EuroScore II differed significantly between treatment groups (6.6%±5.6%, 1.7%±1.5% and 3.6%±2.7% for Mitraclip, surgical repair and replacement, respectively, p<0.001). In-hospital mortality for the 3 groups were 3.4%, 1.6% and 8.3%, respectively (p=0.091). Overall, surgical repair patients had higher 4-year survival (HR 0.40 (95% CI 0.26 to 0.63), p<0.001) and fewer combined end points (HR 0.51 (95% CI 0.32 to 0.80), p<0.001) compared with surgical replacement and Mitraclip patients. However, patients undergoing Mitraclip for isolated, primary mitral regurgitation achieved very good long-term survival.

Conclusion

The multidisciplinary heart team assigned only low-risk patients with favourable anatomy to surgical repair, while high-risk patients underwent Mitraclip or surgical replacement. This strategy was associated with lower than expected in-hospital mortality for Mitraclip patients and high 4-year survival rates for patients undergoing surgical or percutaneous repair of isolated primary mitral regurgitation.
Renormalization of scalar field theories in rational spacetime dimensions
Authors: Gracey J. A.
Published: July 2020

We renormalize various scalar field theories with a $$\phi ^n$$ϕn self interaction such as $$n=5$$n=5, 7 and 9 in their respective critical dimensions which are non-integer. The renormalization group functions for the O(N) symmetric extensions are also computed.
Erratum to: Cosmological framework for renormalization group extended gravity at the action level
Authors: Bertini Nicolas R. , Hipólito-Ricaldi Wiliam S. , de Melo-Santos Felipe , Rodrigues Davi C.
Published: July 2020

The original version of this article used both the symbols
SECOND-ORDER STOCHASTIC VOLATILITY ASYMPTOTICS AND THE PRICING OF FOREIGN EXCHANGE DERIVATIVES
Authors: PELLEGRINO TOMMASO
Published: July 2020

We consider models for the pricing of foreign exchange derivatives, where the underlying asset volatility as well as the one for the foreign exchange rate are stochastic. Under this framework, singular perturbation methods have been used to derive first-order approximations for European option prices. In this paper, based on a previous result for the calibration and pricing of single underlying options, we derive the second-order approximation pricing formula in the two-dimensional case and we apply it to the pricing of foreign exchange options.
Protein–Protein Interaction Methods and Protein Phase Separation
Authors: Savojardo Castrense , Martelli Pier Luigi , Casadio Rita
Published: July 2020

In the last decade, newly developed experimental methods have made it possible to highlight that macromolecules in the cell milieu physically interact to support physiology. This has shifted the problem of protein–protein interaction from a microscopic, electron-density scale to a mesoscopic one. Further, nowadays there is increasing evidence that proteins in the nucleus and in the cytoplasm can aggregate in membraneless organelles for different physiological reasons. In this scenario, it is urgent to face the problem of biomolecule functional annotation with efficient computational methods, suited to extract knowledge from reliable data and transfer information across different domains of investigation. Here, we revise the present state of the art of our knowledge of protein–protein interaction and the computational methods that differently implement it. Furthermore, we explore experimental and computational features of a set of proteins involved in phase separation.
Rotameric Isomers of La2@C80 & Dodecafluoro-Subphthalocyanine Conjugate: Computational Characterization
Authors: Slanina Zdeněk , Uhlík Filip , Feng Lai , Akasaka Takeshi , Lu Xing , Adamowicz Ludwik
Published: July 2020

Stability and spectra of rotamers of a previously via Prato reaction prepared conjugate of dimetallofullerene La2@C80 and dodecafluoro-subphthalocyanine with summary formula C113H10BF12La2N7O and bridging over the cage C–C bond between five- and six-membered rings are calculated. The inter-rotameric energetics is evaluated at the M06-2X/6-311G* ∼ SDD level while the entropy term with the M06-2X/3-21G ∼ SDD approach. The rotamer most-populated at room and higher temperatures has a structure in which both the nitrogen atom of the pyrrolidine ring and the dodecafluoro-subphthalocyanine moiety are inclined toward the five-membered ring belonging to the bridged-over C–C bond. The vibrational and electronic spectra are simulated and the latter spectrum agrees with the observed features. The calculated nanocarbon system is about the largest of its type computationally treated so far.
Therapeutic potential of muscle growth promoters in a stress urinary incontinence model
Authors: Yang Jun , Balog Brian , Deng Kangli , Hanzlicek Brett , Rietsch Anna , Kuang Mei , Hatakeyama Shinji , Lach-Trifilieff Estelle , Zhu Hui , Damaser Margot S.
Published: July 2020

Weakness of urinary sphincter and pelvic floor muscles can cause insufficient urethral closure and lead to stress urinary incontinence. Bimagrumab is a novel myostatin inhibitor that blocks activin type II receptors, inducing skeletal muscle hypertrophy and attenuating muscle weakness. β2-Adrenergic agonists, such as 5-hydroxybenzothiazolone derivative (5-HOB) and clenbuterol, can enhance muscle growth. We hypothesized that promoting muscle growth would increase leak point pressure (LPP) by facilitating muscle recovery in a dual-injury (DI) stress urinary incontinence model. Rats underwent pudendal nerve crush (PNC) followed by vaginal distension (VD). One week after injury, each rat began subcutaneous (0.3 mL/rat) treatment daily in a blinded fashion with either bimagrumab (DI + Bim), clenbuterol (DI + Clen), 5-HOB (DI + 5-HOB), or PBS (DI + PBS). Sham-injured rats underwent sham PNC + VD and received PBS (sham + PBS). After 2 wk of treatment, rats were anesthetized for LPP and external urethral sphincter electromyography recordings. Hindlimb skeletal muscles and pelvic floor muscles were dissected and stained. At the end of 2 wk of treatment, all three treatment groups had a significant increase in body weight and individual muscle weight compared with both sham-treated and sham-injured rats. LPP in DI + Bim rats was significantly higher than LPP of DI + PBS and DI + Clen rats. There were more consistent urethral striated muscle fibers, elastin fibers in the urethra, and pelvic muscle recovery in DI + Bim rats compared with DI + PBS rats. In conclusion, bimagrumab was the most effective for increasing urethral pressure and continence by promoting injured external urethral sphincter and pelvic floor muscle recovery.
IL-10 treatment decreases blood pressure in male, but not female, spontaneously hypertensive rats
Authors: Gillis Ellen E. , Musall Jacqueline B. , Baban Babak , Sullivan Jennifer C.
Published: July 2020

Interleukin-10 (IL-10) is an anti-inflammatory cytokine that induces nitric oxide (NO) production. IL-10 supplementation has been previously shown to lower blood pressure (BP) in male hypertensive mice, but the effect of exogenous IL-10 in hypertensive female rodents has not been studied. For the present study, we hypothesized that chronic infusion of IL-10 in hypertensive rats would lower BP concomitant with an increase in renal NO synthase (NOS) activity. Male and female spontaneously hypertensive rats (SHRs; 12 wk old) were randomized to receive IL-10 infusion by subcutaneous minipump (3.5 µg·kg−1·day−1) or serve as sham controls ( n = 4–6 rats per treatment per sex). BP was measured by tail cuff before and after 2 wk of treatment. Renal T cells and IL-10 were measured by flow cytometry, and NOS activity was determined by conversion of radiolabeled arginine to radiolabeled citrulline. Female SHRs had greater IL-10+ renal cells than male SHRs and greater expression of the IL-10 receptor at baseline. BP did not change in female SHRs treated with IL-10, but BP significantly decreased following IL-10 infusion in male SHRs. Contrary to our hypothesis, NOS enzymatic activity decreased with IL-10 treatment in the renal inner medulla and cortex of both sexes. Renal regulatory T cells also decreased in both sexes after IL-10 treatment. In conclusion, despite male SHRs having less IL-10 and IL-10 receptor expression in the kidney compared with female SHRs, exogenous IL-10 selectively decreased BP only in male SHRs. Furthermore, our data suggest that exogenous IL-10-induced decreases in BP in male SHRs are not dependent on upregulating renal NOS activity.
Mitochondrial transplantation by intra-arterial injection for acute kidney injury
Authors: Doulamis Ilias P. , Guariento Alvise , Duignan Thomas , Kido Takashi , Orfany Arzoo , Saeed Mossab Y. , Weixler Viktoria H. , Blitzer David , Shin Borami , Snay Erin R. , Inkster James A. , Packard Alan B. , Zurakowski David , Rousselle Thomas , Bajwa Amandeep , Parikh Samir M. , Stillman Isaac E. , del Nido Pedro J. , McCully James D.
Published: July 2020

Acute kidney injury is a common clinical disorder and one of the major causes of morbidity and mortality in the postoperative period. In this study, the safety and efficacy of autologous mitochondrial transplantation by intra-arterial injection for renal protection in a swine model of bilateral renal ischemia-reperfusion injury were investigated. Female Yorkshire pigs underwent percutaneous bilateral temporary occlusion of the renal arteries with balloon catheters. Following 60 min of ischemia, the balloon catheters were deflated and animals received either autologous mitochondria suspended in vehicle or vehicle alone, delivered as a single bolus to the renal arteries. The injected mitochondria were rapidly taken up by the kidney and were distributed throughout the tubular epithelium of the cortex and medulla. There were no safety-related issues detected with mitochondrial transplantation. Following 24 h of reperfusion, estimated glomerular filtration rate and urine output were significantly increased while serum creatinine and blood urea nitrogen were significantly decreased in swine that received mitochondria compared with those that received vehicle. Gross anatomy, histopathological analysis, acute tubular necrosis scoring, and transmission electron microscopy showed that the renal cortex of the vehicle-treated group had extensive coagulative necrosis of primarily proximal tubules, while the mitochondrial transplanted kidney showed only patchy mild acute tubular injury. Renal cortex IL-6 expression was significantly increased in vehicle-treated kidneys compared with the kidneys that received mitochondrial transplantation. These results demonstrate that mitochondrial transplantation by intra-arterial injection provides renal protection from ischemia-reperfusion injury, significantly enhancing renal function and reducing renal damage.
Impact of Saliva and Cariogenic Microbiota on the Chemotherapy-Induced Oral Mucositis in Oncopediatric Patients: A Preliminary Longitudinal Study
Authors: Costa Raphael Cavalcante , Bezerra Paula Maria Maracajá , Damascena Lecidamia Cristina Leite , Ribeiro Isabella Lima Arrais , Bonan Paulo Rogério Ferreti , Sousa Simone Alves de , Almeida Leopoldina de Fátima Dantas , Valença Ana Maria Gondim
Published: July 2020

This study aims to evaluate the salivary parameters and cariogenic microbiota of pediatric oncological patients and their correlation with severe oral mucositis (SOM). A preliminary longitudinal study included patients in the age range from 4 to 18 years (n = 26), with diagnosis of primary cancer, who were followed up before and after time intervals of two, five, and ten weeks of induction chemotherapy. Oral mucosa examinations were performed by means of the modified Oral Assessment Guide (OAG) by calibrated examiners (κ > 0.70). Saliva analysis (unstimulated saliva flow (USF), clinical saliva viscosity (CSV), and pH) and microbiological (total Streptococcus (TS) and Streptococcus of the mutans group (SMG)) tests were performed using unstimulated saliva. The data were analyzed by the Wilcoxon and Spearman Correlation tests (α = 5%). The patients were predominantly of the female sex (n = 15; 57.7%), adolescents (n = 15; 57.7%), and patients with hematological tumors (n = 21; 80.8%). SOM was more frequent in the tenth week (n = 7; 28.6%). The values of USF, CSV, pH, TS, and SMG were not changed by the institution of chemotherapy (

p
>
0.05

). These values were correlated with SOM and the time, TS and SMG, and CSV and SMG. The salivary and microbiological parameters investigated did not influence the severity of oral mucositis in the pediatric patients oncological..
Exploration of the Antimicrobial and Catalytic Properties of Gold Nanoparticles Greenly Synthesized by Cryptolepis buchanani Roem. and Schult Extract
Authors: Wongyai Kamonpan , Wintachai Phitchayapak , Maungchang Rasimate , Rattanakit Parawee
Published: July 2020

A green, simple, and rapid synthesis of gold nanoparticles using plant extract, Cryptolepis buchanani Roem. and Schult, and their applications are first described in this paper. The formation of gold nanoparticles was visually observed by the appearance of a ruby red color, which was further indicated by an absorption peak at 530 nm in UV-Vis spectroscopy. Optimization of reaction parameters for the gold nanoparticles was also investigated. Various analytical techniques were employed as part of the process of characterizing the resulting gold nanoparticles. Fourier transform infrared (FTIR) analysis revealed that the phenol compounds present in the extract were responsible for gold(III) reduction and stabilization of gold nanoparticles. Transmission electron microscopy (TEM) analysis showed that the gold nanoparticles were spherical in shape with an average diameter of 11 nm. Powder X-ray diffraction (XRD) pattern indicated that the green synthesis approach produced highly crystalline, face-centered cubic gold nanoparticles. Energy-dispersive X-ray spectroscopy (EDS) measurements confirmed the presence of elemental gold in the prepared nanoparticles. The negative zeta potential value of gold nanoparticles was found to be -30.28 mV. The green synthesized gold nanoparticles expressed effective antibacterial activity against Staphylococcus aureus, methicillin-resistant Staphylococcus aureus, and Acinetobacter baumannii and exhibited an excellent catalytic property in terms of its reduction ability of methylene blue.
Comparing the Effect of Monofocal and Multifocal Intraocular Lenses on Macular Surgery
Authors: Altun A.
Published: July 2020

Aim. To compare the effects of previously implanted monofocal and multifocal intraocular lenses (IOL) on macular surgery. Methods. Seventy eyes of 70 patients with epiretinal membrane (ERM) and symptomatic vitromacular traction syndrome that previously had IOL implantation for cataract surgery were included in this prospective randomized clinical trial. Cases were divided into two groups. Group 1 and Group 2 were composed of eyes with monofocal and multifocal IOLs, respectively. The effects of refraction error and IOL decentration at the time of macular surgery performed for ERM and ILM peeling, according to the lens type, were investigated. Pars plana vitrectomy (PPV) was performed to peel ERM and ILM in all cases. Complete ophthalmological examination, fundus fluorescein angiography, and optical coherence tomography imaging were made to all cases, preoperatively and postoperatively. Results. The mean BCVA in Group 1 and Group 2 improved from 0.69 ± 0.15 and 0.38 ± 0.14 logMAR to 0.40 ± 0.14 and 0.10 ± 0.04 logMAR, respectively, at the 6th month. There was no statistically significant difference between the groups in terms of the mean spherical refraction error (P>0.05) and IOL decentration level (P>0.05). The mean time required for macular surgery in Group 2 was statistically significantly longer than that for Group 1 (P<0.05). There was no statistically significant relationship between IOL decentration and macular surgery time in Group 1 (P>0.05), but there it was found in Group 2 (P<0.05). In Group 2, there was a positive correlation between IOL decentration and macular surgery time. Conclusion. In cases with multifocal IOL implants, especially with lens decentration, the time of macular surgery for ERM and ILM peeling during PPV is longer than that of eyes with monofocal IOL due to fluctuations in the clarity of the surgeon’s view.
Estimation of Tail Risk and Moments Using Option Prices with a Novel Pricing Model under a Distorted Lognormal Distribution
Authors: Chen Yan , Cai Ya , Zheng Chengli
Published: July 2020

Risk measures based on the trading option prices in the market are forward-looking, such as VIX. We propose a new method combining distorted lognormal distribution with interpolation to price options accurately and then estimate tail risk. Our method can price the option of any strikes between the maximum and the minimum value of strikes in the real market, which reduces the instability and inaccuracy of using the limited option to measure the risk. In addition, our novel method treats the underlying asset price as a stochastic indicator rather than a fixed indicator as described in previous research studies for risk measurement. Moreover, even if the available sample size is very small, we can measure the risk stably and precisely after interpolation. Finally, the empirical test results of SP500 market show that this method has good performance, especially for the option markets with sparse strikes.
Neuregulin-1β Protects the Rat Diaphragm during Sepsis against Oxidative Stress and Inflammation by Activating the PI3K/Akt Pathway
Authors: Liu Hua , Weng Xiao-jian , Yao Jun-yan , Zheng Jun , Lv Xiang , Zhou Xu-hui , Jiang Hong , Li Shi-tong
Published: July 2020

Sepsis-induced diaphragm dysfunction (SIDD) which is mainly characterized by decrease in diaphragmatic contractility has been identified to cause great harms to patients. Therefore, there is an important and pressing need to find effective treatments for improving SIDD. In addition, acetylcholinesterase (AChE) activity is a vital property of the diaphragm, so we evaluated both diaphragmatic contractility and AChE activity. Though neuregulin-1β (NRG-1β) is known to exert organ-protective effects in some inflammatory diseases, little is known about the potential of NRG-1β therapy in the diaphragm during sepsis. Our study was aimed at exploring the effects of NRG-1β application on diaphragmatic contractility and AChE activity during sepsis. Proinflammatory cytokines, muscle injury biomarkers in serum, contractile force, AChE activity, proinflammatory cytokines, oxidative parameters, histological condition, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining, and expression of phosphoinositide 3-kinase (PI3K)/protein kinase B (PKB/Akt) signaling proteins in the diaphragm were measured and compared between nonseptic and septic groups with or without NRG-1β treatment. In vitro, the effects of NRG-1β on reactive oxygen species (ROS) production in the lipopolysaccharide- (LPS-) stimulated L6 rat muscle skeletal cells with or without the Akt inhibitor MK-2206 were detected. NRG-1β inhibited proinflammatory cytokine release and muscle injury biomarkers soaring in serum and improved the sepsis-induced diaphragm dysfunction and AChE activity decrease significantly during sepsis. Meanwhile, the inflammatory response, oxidative stress, pathological impairment, and cell apoptosis in the diaphragm were mitigated by NRG-1β. And NRG-1β activated the PI3K/Akt signaling in the diaphragm of septic rats. Elevated ROS production in the LPS-stimulated L6 rat skeletal muscle cells was reduced after treatment with NRG-1β, while MK-2206 blocked these effects of NRG-1β. In conclusion, our findings underlined that NRG-1β could reduce circulating levels of proinflammatory cytokines in rats with sepsis, adjust diaphragmatic proinflammatory cytokine level, mitigate diaphragmatic oxidative injury, and lessen diaphragm cell apoptosis, thereby improving diaphragmatic function, and play a role in diaphragmatic protection by activating PI3K/Akt signaling.
Improving the Slippage Resistance of Successors of the Mars Instrument “Heat Flow Property Package Instrument” (HP3) Using Bekker’s Spaced-Linked Track
Authors: Reershemius Siebo
Published: July 2020

The “Heat Flow Property Package Instrument” (HP3) is part of NASA’s current Mars mission “InSight”, which was launched in 2018 and currently operates on the surface of Mars. The instrument needs to remain at its initial position and orientation during operation. Although the landing site can have significant tilt and can be covered with low cohesion soil, any mechanical excitation might make the instrument slip. Therefore, the instrument is using a tailored feet design, which can withstand lateral loads. Future instruments might require higher resistance against slip. This can be due to stronger tilted landing sites or due to higher shocks emitted from stronger penetration probes. This paper introduces a novel design for those instruments based on the idea of the “spaced-link track” of Bekker to further minimize slippage. This design concept is originally used on tracks of heavy machinery. It is presented how the major design feature can be incorporated into the current design. A newly developed analytical-numerical model is utilized to estimate the track force of the new design. The paper closes with a design study at which the new design and the current design are compared to each other for different sized feet.
Cannabinoid Effects on Experimental Colorectal Cancer Models Reduce Aberrant Crypt Foci (ACF) and Tumor Volume: A Systematic Review
Authors: Orrego-González Eduardo , Londoño-Tobón Luisa , Ardila-González José , Polania-Tovar Diego , Valencia-Cárdenas Ana , Velez-Van Meerbeke Alberto
Published: July 2020

Objective. Colorectal cancer represents a heavy burden for health systems worldwide, being the third most common cancer worldwide. Despite the breakthroughs in medicine, current chemotherapeutic options continue to have important side effects and may not be effective in preventing disease progression. Cannabinoids might be substances with possible therapeutic potential for cancer because they can attenuate the side effects of chemotherapy and have antiproliferative and antimetastatic effects. We aim to determine, through a systematic review of experimental studies performed on animal CRC models, if cannabinoids can reduce the formation of preneoplastic lesions (aberrant crypt foci), number, and volume of neoplastic lesions. Materials and Methods. A systematic, qualitative review of the literature was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guidelines. PubMed, Embase, and Scopus databases were searched. We use the following Medical Subject Headings (MESH) terms in PubMed: “colorectal neoplasms,” “colonic neoplasms,” “colorectal cancer,” “polyps,” “rimonabant,” “cannabidiol,” “cannabinoids,” “azoxymethane,” “xenograft,” and “mice.” Only studies that met the eligibility criteria were included. Results. Eight in vivo experimental studies were included in the analysis after the full‐text evaluation. Seven studies were azoxymethane (AOM) colorectal cancer models, and four studies were xenograft models. Cannabidiol botanical substance (CBD BS) and rimonabant achieved high aberrant crypt foci (ACF) reduction (86% and 75.4%, respectively). Cannabigerol, O‐1602, and URB‐602 demonstrated a high capacity for tumor volume reduction. Induction of apoptosis, interaction with cell survival, growth pathways, and angiogenesis inhibition were the mechanisms extracted from the studies that explain cannabinoids’ actions on CRC. Conclusions. Cannabinoids have incredible potential as antineoplastic agents as experimental models demonstrate that they can reduce tumor volume and ACF formation. It is crucial to conduct more experimental studies to understand the pharmacology of cannabinoids in CRC better.