bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of a tool for identifying and addressing prioritised determinants of quality improvement initiatives led by healthcare professionals: a mixed-methods study
Authors: van Tuijl Anne A. C. , Wollersheim Hub C. , Fluit Cornelia R. M. G. , van Gurp Petra J. , Calsbeek Hiske 
Published: October 2020

Abstract
Background
Several frameworks have been developed to identify essential determinants for healthcare improvement. These frameworks aim to be comprehensive, leading to the creation of long lists of determinants that are not prioritised based on being experienced as most important. Furthermore, most existing frameworks do not describe the methods or actions used to identify and address the determinants, limiting their practical value. The aim of this study is to describe the development of a tool with prioritised facilitators and barriers supplemented with methods to identify and address each determinant. The tool can be used by those performing quality improvement initiatives in healthcare practice.

Methods
A mixed-methods study design was used to develop the tool. First, an online survey was used to ask healthcare professionals about the determinants they experienced as most facilitating and most hindering during the performance of their quality improvement initiative. A priority score was calculated for every named determinant, and those with a priority score ≥ 20 were incorporated into the tool. Semi-structured interviews with implementation experts were performed to gain insight on how to analyse and address the determinants in our tool.

Results
The 25 healthcare professionals in this study experienced 64 facilitators and 66 barriers when performing their improvement initiatives. Of these, 12 facilitators and nine barriers were incorporated into the tool. Sufficient support from management of the department was identified as the most important facilitator, while having limited time to perform the initiative was considered the most important barrier. The interviews with 16 experts in implementation science led to various inputs for identifying and addressing each determinant. Important themes included maintaining adequate communication with stakeholders, keeping the initiative at a manageable size, learning by doing and being able to influence determinants.

Conclusions
This paper describes the development of a tool with prioritised determinants for performing quality improvement initiatives with suggestions for analysing and addressing these determinants. The tool is developed for those engaged in quality improvement initiatives in practice, so in this way it helps in bridging the research to practice gap of determinants frameworks. More research is needed to validate and develop the tool further.
The Non-hormonal Male Contraceptive Adjudin Exerts its Effects via MAPs and Signaling Proteins mTORC1/rpS6 and FAK-Y407
Authors: Wang Lingling , Yan Ming , Li Huitao , Wu Siwen , Ge Renshan , Wong Chris K C , Silvestrini Bruno , Sun Fei , Cheng C Yan 
Published: October 2020

AbstractAdjudin, 1-(2,4-dichlorobenzyl)-1H-indazole-3-carbohydrazide (formerly called AF-2364), is a nonhormonal male contraceptive, since it effectively induces reversible male infertility without perturbing the serum concentrations of follicle stimulating hormone (FSH), testosterone, and inhibin B based on studies in rats and rabbits. Adjudin was shown to exert its effects preferentially by perturbing the testis-specific actin-rich adherens junction (AJ) at the Sertoli–spermatid interface known as apical ectoplasmic specialization (apical ES), thereby effectively inducing spermatid exfoliation. Adjudin did not perturb germ cell development nor germ cell function. Also, it had no effects on Sertoli cell–cell AJ called basal ectoplasmic specialization (basal ES), which, together with tight junction constitute the blood-testis barrier (BTB), unless an acute dose of adjudin was used. Adjudin also did not perturb the population of spermatogonial stem cells nor Sertoli cells in the testis. However, the downstream signaling protein(s) utilized by adjudin to induce transient male infertility remains unexplored. Herein, using adult rats treated with adjudin and monitored changes in the phenotypes across the seminiferous epithelium between 6 and 96 h in parallel with the steady-state protein levels of an array of signaling and cytoskeletal regulatory proteins, recently shown to be involved in apical ES, basal ES and BTB function. It was shown that adjudin exerts its contraceptive effects through changes in microtubule associated proteins (MAPs) and signaling proteins mTORC1/rpS6 and p-FAK-Y407. These findings are important to not only study adjudin-mediated male infertility but also the biology of spermatogenesis.
Congenital Adrenal Hyperplasia Causing Poor Response to Androgen Deprivation Therapy in Prostate Cancer
Authors: Kinaan Mustafa , Hamidi Oksana , Yau Hanford , Courtney Kevin D , Eraslan Akin , Simon Kenneth 
Published: October 2020

Abstract
Androgen deprivation therapy (ADT) is recommended for the treatment of advanced prostate cancer. Inadequate suppression of testosterone while on ADT poses a clinical challenge and requires evaluation of multiple potential causes, including adrenal virilizing disorders. We present 2 cases of elderly patients with prostate cancer who had undiagnosed congenital adrenal hyperplasia (CAH) driving persistent testosterone elevation during ADT. The first patient is a 73-year-old man who underwent radical prostatectomy on initial diagnosis and was later started on ADT with leuprolide following tumor recurrence. He had a testosterone level of 294.4 ng/dL and prostate-specific antigen (PSA) level of 17.7 ng/mL despite leuprolide use. Additional workup revealed adrenal nodular hyperplasia, elevated 17-hydroxyprogesterone (19 910 ng/dL) and dehydroepiandrosterone sulfate (378 mcg/dL), and 2 mutations of the CYP21A2 gene consistent with simple virilizing CAH. The second patient is an 82-year-old man who received stereotactic radiation therapy at time of diagnosis. He had insufficient suppression of testosterone with evidence of metastatic disease despite treatment with leuprolide and subsequently degarelix. Laboratory workup revealed elevated 17-hydroxyprogesterone (4910 ng/dL) and dehydroepiandrosterone sulfate (312 mcg/dL). Based on clinical, radiographic and biochemical findings, the patient was diagnosed with nonclassic CAH. The first patient initiated glucocorticoid therapy, and the second patient was treated with the CYP17 inhibitor abiraterone in combination with glucocorticoids. Both patients experienced rapid decline in testosterone and PSA levels. Inadequate testosterone suppression during ADT should trigger evaluation for causes of persistent hyperandrogenemia. CAH can lead to hyperandrogenemia and pose challenges when treating patients with prostate cancer.
Shifting away from the business-as-usual approach to research conferences
Authors: Counsell Chelsie W. W. , Elmer Franziska , Lang Judith C. 
Published: October 2020

ABSTRACT
To combat the climate crisis, we need rapid, unprecedented social change. Scientists can play a lead role by signaling to society that we recognize the critical importance of redesigning our business-as-usual approach to research conferences. Traditional research conferences have high CO2 emissions as well as significant financial and travel time costs for participants. Using available technology, early career scientists Chelsie Counsell and Franziska Elmer created a global, virtual, coral reef research conference with live talks, recorded contributions, and networking events. Funding from The Company of Biologists allowed this event to be free, supporting attendance of 2700 subscribers and content contributions from 165 participants from diverse backgrounds and career stages. We provide metrics on content viewership and participation in networking activities, note the success of incorporating regionally focused sub-events, and discuss the emergence of a collaborative research project. We highlight the broad accessibility of virtual conferences as well as their increased flexibility in programming, health benefits, and cost savings. Our approach to organizing and hosting a global, low-carbon emission research conference is documented. Finally, we propose a hybrid approach to future conferences with virtually connected remote (sub-regional or local) hubs.
Insulin/IGF signaling and TORC1 promote vitellogenesis via inducing juvenile hormone biosynthesis in the American cockroach
Authors: Zhu Shiming , Liu Fangfang , Zeng Huanchao , Li Na , Ren Chonghua , Su Yunlin , Zhou Shutang , Wang Guirong , Palli Subba Reddy , Wang Jian , Qin Yiru , Li Sheng 
Published: October 2020

ABSTRACT
Vitellogenesis, including vitellogenin (Vg) production in the fat body and Vg uptake by maturing oocytes, is of great importance for the successful reproduction of adult females. The endocrinal and nutritional regulation of vitellogenesis differs distinctly in insects. Here, the complex crosstalk between juvenile hormone (JH) and the two nutrient sensors insulin/IGF signaling (IIS) and target of rapamycin complex1 (TORC1), was investigated to elucidate the molecular mechanisms of vitellogenesis regulation in the American cockroach, Periplaneta americana. Our data showed that a block of JH biosynthesis or JH action arrested vitellogenesis, in part by inhibiting the expression of doublesex (Dsx), a key transcription factor gene involved in the sex determination cascade. Depletion of IIS or TORC1 blocked both JH biosynthesis and vitellogenesis. Importantly, the JH analog methoprene, but not bovine insulin (to restore IIS) and amino acids (to restore TORC1 activity), restored vitellogenesis in the neck-ligated (IIS-, TORC1- and JH-deficient) and rapamycin-treated (TORC1- and JH-deficient) cockroaches. Combining classic physiology with modern molecular techniques, we have demonstrated that IIS and TORC1 promote vitellogenesis, mainly via inducing JH biosynthesis in the American cockroach.
Mitochondrial dysfunction triggers a catabolic response in chondrocytes via ROS-mediated activation of the JNK/AP1 pathway
Authors: Ansari Mohammad Y. , Ahmad Nashrah , Voleti Sriharsha , Wase Saima J. , Novak Kimberly , Haqqi Tariq M. 
Published: October 2020

ABSTRACT
Mitochondrial function is impaired in osteoarthritis (OA) but its impact on cartilage catabolism is not fully understood. Here, we investigated the molecular mechanism of mitochondrial dysfunction-induced activation of the catabolic response in chondrocytes. Using cartilage slices from normal and OA cartilage, we showed that mitochondrial membrane potential was lower in OA cartilage, and that this was associated with increased production of mitochondrial superoxide and catabolic genes [interleukin 6 (IL-6), COX-2 (also known as PTGS2), MMP-3, -9, -13 and ADAMTS5]. Pharmacological induction of mitochondrial dysfunction in chondrocytes and cartilage explants using carbonyl cyanide 3-chlorophenylhydrazone increased mitochondrial superoxide production and the expression of IL-6, COX-2, MMP-3, -9, -13 and ADAMTS5, and cartilage matrix degradation. Mitochondrial dysfunction-induced expression of catabolic genes was dependent on the JNK (herein referring to the JNK family)/activator protein 1 (AP1) pathway but not the NFκB pathway. Scavenging of mitochondrial superoxide with MitoTEMPO, or pharmacological inhibition of JNK or cFos and cJun, blocked the mitochondrial dysfunction-induced expression of the catabolic genes in chondrocytes. We demonstrate here that mitochondrial dysfunction contributes to OA pathogenesis via JNK/AP1-mediated expression of catabolic genes. Our data shows that AP1 could be used as a therapeutic target for OA management.
This article has an associated First Person interview with the first author of the paper.
The New ACSM Recommendations for Preventing Cardiovascular Events at Fitness Facilities
Authors: Riebe Deborah , Baggish Aaron L. , Franklin Barry A. , Jaworski Carrie A. , Thompson Paul D. 
Published: October 2020

Apply It!
This article will help readers to:
• understand the cardiovascular risks associated with physical activity and
• learn more about the steps that exercise professionals can take to promote safety in health fitness facilities.
Value of MRI and diffusion-weighted imaging in diagnosing normal-sized pelvic lymph nodes metastases in patients with cervical cancer
Authors: Song Qingling , Yu Yanyan , Zhang Xiaomiao , Zhu Yanmei , Luo Yahong , Yu Tao , Sun Jiayi , Liu Fan , Dong Yue 
Published: October 2020

Objectives:
To investigate the value of conventional MRI and diffusion-weighted imaging (DWI) in diagnosing normal-sized pelvic lymph nodes metastases in patients with cervical cancer.

Methods:
102 patients with cervical cancer who underwent MRI and DWI scan were included. 137 lymph nodes were analyzed, including 44 metastatic lymph nodes (MLNs) and 93 non-metastatic lymph nodes (non-MLNs). The morphology and apparent diffusion coefficient (ADC) value of lymph nodes were measured including short-axis diameter (DS), long-axis diameter (DL), ratio of short-to-long-axis diameter (DR), fatty hilum, asymmetry, ADCmax, ADCmean and ADCmin. The Mann-Whitney U-test, independent sample t-test and Chi-square test were employed to compare the differences of all criteria between MLNs and non-MLNs. Logistic regression and decision tree were used to develop the combined diagnostic model. ROC analyses were used to evaluate the diagnostic performance.

Results:
The DS and DR of MLNs were significantly higher than those of non-MLNs (p &lt; 0.05), the ADCmax, ADCmean and ADCmin of MLNs were significantly lower than those of non-MLNs (p &lt; 0.05). Presence of fatty hilum and asymmetric lymph nodes between MLNs and non-MLNs were significantly different (p＜0.05). Combined measurement of ADCmin, DS and DR had the highest AUC 0.937 with 90.9% sensitivity and 87.1% specificity. The accuracy of decision tree was 88.3%.

Conclusion:
MRI with DWI had potential in diagnosing normal-sized pelvic lymph nodes metastases in patients with cervical cancer. The combined evaluation of DS, DR and ADCmin of lymph nodes and decision tree of the combined measure showed better diagnostic performances than sole criteria.

Advances in knowledge:
The short-axis diameter, ratio of short-to-long-axis diameter and ADCmin of lymph nodes have moderate value in the diagnosis of the metastases of the normal-sized lymph nodes for the patient with cervical cancer as the sole indices. The combined evaluation of DS, DR and ADCmin is much more valuable in the detection of metastatic lymph nodes.
The safety of primary surgical excision of small deep indeterminate musculoskeletal soft tissue masses
Authors: Calleja Michèle , Afzaal Qasim , Saifuddin Asif 
Published: October 2020

Objective:
To determine the suitability of primary excision of small indeterminate deep soft tissue masses presenting to a tertiary musculoskeletal oncology service.

Methods and materials:
Review of all patients referred to a specialist musculoskeletal oncology service over a 20-month period with a deep indeterminate soft tissue mass by non-contrast MRI criteria that was recommended for primary surgical excision due to relatively small size (&lt;30 mm). Data collected included age, gender, site and maximal size of the lesion, and final histological diagnosis for excised lesions.

Results:
85 patients were included, mean lesion size being 12 mm (range 5–29 mm). Primary surgical resection had been undertaken in 69 cases (81.2%) by the conclusion of data collection, 36 males and 33 females with mean age of 45.6 years (range 11–80 years). Of these, 11 cases (15.9%) were non-neoplastic, 53 (76.8%) were benign, 1 (1.4%) was intermediate grade, while 4 (5.8%) were malignant including 3 synovial sarcomas. Two of these were treated with re-excision of the tumour bed showing no residual disease, with no evidence of local recurrence at a mean of 10.7 months post-excision.

Conclusion:
Primary surgical excision of small deep soft tissue masses that are indeterminate by non-contrast MRI criteria is considered a safe procedure when undertaken in a specialist musculoskeletal oncology service, with only 4 of 69 cases (5.8%) being malignant.

Advances in knowledge:
Small indeterminate deep soft tissue masses can safely be treated with primary excision in the setting of a specialist musculoskeletal oncology service.
Rectal spacer hydrogel in 1.5T MR-guided and daily adapted SBRT for prostate cancer: dosimetric analysis and preliminary patient-reported outcomes
Authors: Alongi Filippo , Rigo Michele , Figlia Vanessa , Cuccia Francesco , Giaj-Levra Niccolò , Nicosia Luca , Ricchetti Francesco , Vitale Claudio , Sicignano Gianluisa , De Simone Antonio , Naccarato Stefania , Ruggieri Ruggero , Mazzola Rosario 
Published: October 2020

Objective:
The main aim of the current analysis was to explore the hypothetical advantages using rectal spacer during 1.5T MR-guided and daily adapted prostate cancer stereotactic body radiotherapy (SBRT) compared to a no-rectal spacer hydrogel cohort of patients.

Methods:
The SBRT-protocol consisted of a 35 Gy schedule delivered in 5 fractions. Herein, we present a dosimetric analysis between spacer and no-spacer patients. Furthermore, treatment tolerability and feasibility were preliminarily assessed according to clinicians-reported outcomes at the end of treatment and patient-reported outcomes measures (PROMs) in both arms. Toxicity and quality of life were assessed at baseline and after treatment using the Common Terminology Criteria for Adverse Events v. 5.0, International Prostatic Symptoms Score, ICIQ-SF, IIEF-5, and EORTC-QLQ-C30 and PR-25 questionnaires.

Results:
120 plans (pre- and daily adaptive SBRT planning) were analyzed in 20 patients (10 patients in spacer group and 10 patients in no-spacer group) treated using 1.5T MR-guided adaptive SBRT. Statistically significant dosimetric advantages were observed in favor of the spacer insertion, improving the planning target volume coverage in terms of V33.2Gy &gt;95% and planning target volume 37.5 Gy &lt;2% mainly during daily-adapted SBRT. Also, rectum V32, V28 and V18Gy and bladder V35Gy &lt;1 cc were significantly reduced in the spacer cohort. Concerning the PROMS, all questionnaires showed no difference between the pre- and post-SBRT evaluation in both arms, excepting the physical functioning item of EORTC QLQ-C30 questionnaire that was declined in the no-spacer group.

Conclusion:
These preliminary results strongly suggest the adoption of perirectal spacer due to dosimetric advantages not only for rectal sparing but also for target coverage. Longer follow-up is required to validate the clinical impact in terms of clinicians-reported toxicity and PROMs.

Advances in knowledge:
This the first experience reporting preliminary data concerning the potential dosimetric impact of rectal hydrogel spacer on MR-guided SBRT for prostate cancer.
Η μάσκα στη σύγχρονη πανδημία: κοινωνιολογικές προσεγγίσεις και ζητήματα ερμηνείας
Authors: Valasaki Maria 
Published: October 2020

Η πανδημία που προκλήθηκε από τον κορωνοϊό SARS-CoV-2 ανέδειξε πληθώρα ζητημάτων, τα οποία χρήζουν διερεύνησης υπό σύγχρονες διεπιστημονικές οπτικές. Ένα από τα θέματα που έχουν απασχολήσει ιδιαίτερα όχι μόνο τις κοινωνικές επιστήμες αλλά το κάθε άτομο χωριστά είναι αυτό της μάσκας, το οποίο τίθεται στο σύντομο αυτό κείμενο στο επίκεντρο της συζήτησης. Η χρήση της μάσκας προβληματοποιείται σε σχέση με τις αισθήσεις, όπως τις προσεγγίζει ο Simmel (2017), ενώ οι τελευταίες ανοίγουν το δρόμο για διερωτήσεις σχετικά με τις έντονες κοινωνικές αλλαγές των τελευταίων μηνών. Συγκεκριμένα, η χρήση της μάσκας φαίνεται να επηρεάζει όχι αυτή καθαυτήν την αίσθηση της ακοής, αλλά κυρίως τον τρόπο με τον οποίο κατανοούμε τους άλλους και τον εαυτό μας μέσω αυτής και τον τρόπο που χρησιμοποιούμε το σώμα μας σε σχέση με αυτήν˙ φαίνεται να δημιουργούνται νέα επικοινωνιακά μονοπάτια. Από την προβληματοποίηση των αισθήσεων φαίνεται ότι ο ιατρικός λόγος διαπλέκεται με τον πολιτικό και παρεισφρέει στην καθημερινότητα αφήνοντας τα μοντέλα εξουσίας να διαφανούν, δημιουργώντας παράλληλα σχήματα όπως απομόνωση-ασφάλεια, τα οποία μορφοποιούν το σύγχρονο επικοινωνιακό πλαίσιο και τον εαυτό. Υπό μια, επομένως, σύντομη «καλειδοσκοπική» οπτική, η μάσκα κατανοείται ως σύμβολο με πολλαπλά νοήματα, προσ-καλώντας στην απόδοση σημασιών και στον επαναπροσδιορισμό εννοιών.
Characterization of sulfated polysaccharide activity against virulent Plasmodium falciparum PHISTb/RLP1 protein
Authors: Mutisya Jennifer M. , Mobegi Victor A. , Kinyua Johnson K. , Kivecu Martha N. , Okoth Raphael O. , Chemwor Gladys C. , Mwakio Edwin W. , Cheruiyot Agnes C. , Yeda Redempta A. , Okello Charles O. , Juma Jackline A. , Opot Benjamin H. , Juma Dennis W. , Roth Amanda L. , Akala Hosea M. , Andagalu Ben M. 
Published: October 2020

Background: The emergence of artemisinin resistance in South East Asia calls for urgent discovery of new drug compounds that have antiplasmodial activity. Unlike the classical compound screening drug discovery methods, the rational approach involving targeted drug discovery is less cumbersome and therefore key for innovation of new antiplasmodial compounds. Plasmodium falciparum (Pf) utilizes the process of host erythrocyte remodeling using Plasmodium-helical interspersed sub-telomeric domain (PHIST) containing proteins, which are amenable drug targets. The aim of this study is to identify inhibitors of PHIST from sulfated polysaccharides as new antimalarials. Methods: 251 samples from an ongoing study of epidemiology of malaria and drug resistance sensitivity patterns in Kenya were sequenced for PHISTb/RLP1 gene using Sanger sequencing. The sequenced reads were mapped to the reference Pf3D7 protein sequence of PHISTb/RLP1 using CLC Main Workbench. Homology modeling of both reference and mutant protein structures was achieved using the LOMETs tool. The models were refined using ModRefiner for energy minimization. Ramachandran plot was generated by ProCheck to assess the conformation of amino acids in the protein model. Protein binding sites predictions were assessed using FT SITE software. We searched for prospective antimalarials from PubChem. Docking experiments were achieved using AutoDock Vina and analysis results visualized in PyMOL. Results: Sanger sequencing generated 86 complete sequences. Upon mapping of the sequences to the reference, 12 non-synonymous single nucleotide polymorphisms were considered for mutant protein structure analysis. Eleven drug compounds with antiplasmodial activity were identified. Both modelled PHISTb/RLP1 reference and mutant structures had a Ramachandran score of >90% of the amino acids in the favored region. Ten of the drug compounds interacted with amino acid residues in PHISTb and RESA domains, showing potential activity against these proteins. Conclusion: These interactions provide lead compounds for new anti-malarial molecules. Further in vivo testing is recommended.
NOVOS ESPAÇOS DE AFETO E CUIDADO EM TEMPOS DE ISOLAMENTO SOCIAL
Authors: Dos Santos Célio Moacir , Da Silva Janneyde Pascoal , Paiva Jair 
Published: October 2020

As circunstâncias impostas pelo isolamento social em virtude da pandemia acarretaram mudanças na dinâmica de um projeto denominado “Cuide-se”. Anteriormente de caráter presencial e depois se adequando para um modelo não presencial com uso de aplicativos de mensagens instantâneas e dispositivos de videochamadas. Objetivou-se com o projeto oferecer acolhimento aos estudantes. Utilizou-se dos pressupostos de Bardin (2011), da teoria do Discurso do Sujeito Coletivo (DSC) de Lefèvre e Lefèvre (2005) e das relações de grupo de acordo com Lane (2003). Constataram-se grandes impactos relacionados à saúde mental dos estudantes e como estes interferem e prejudicam suas rotinas.