bluuebunny/crossref_metadata_2025 huggingface dataset:
Treatment outcomes for patients with metastatic castrate‐resistant prostate cancer following docetaxel for hormone‐sensitive disease
Authors: Schmidt Andrew , Anton Angelyn , Shapiro Julia , Wong Shirley , Azad Arun , Kwan Edmond , Spain Lavinia , Muthusamy Arun , Torres Javier , Parente Phillip , Parnis Francis , Goh Jeffrey , Joshua Anthony M. , Pook David , Gibbs Peter , Tran Ben , Weickhardt Andrew
Published: September 2020

Aim

Optimal treatment for newly diagnosed metastatic hormone‐sensitive prostate cancer (mHSPC) has evolved, with many patients deriving benefit from the addition of docetaxel to androgen deprivation therapy (D‐ADT). This study sought to define the therapy used and associated activity following D‐ADT.

Methods

Retrospective analysis of patients with mHSPC treated with one or more cycles of D‐ADT who were identified from a prospectively maintained multisite prostate cancer database of patients treated in a community or academic center setting in Australia. The primary endpoint of this study was first‐line time to treatment failure (1L TTF) for subsequent treatment of metastatic Castrate Resistant Prostate Cancer (mCRPC), with secondary endpoints of prostate‐specific antigen (PSA) reduction >50% and time from 1L to second‐line (2L) treatment initiation.

Results

A total of 93 patients received D‐ADT for mHSPC, 85 (91%) had subsequent treatment for mCRPC. Median time to mCRPC (biochemical, clinical or radiographic) had been 14.8 months (95% confidence interval [CI], 11.9–16.5). 1L treatment was enzalutamide 47 patients (55%), abiraterone 23 (27%), cabazitaxel 7 (8%), docetaxel 4 (5%) and other therapies 4 (5%). Median 1L TTF was 6.3 months (95% CI, 4.9–7.6), PSA > 50% reduction was achieved in 32 of 89 patients (36%), median time from 1L to second‐line treatment was 7.3 months (1.3–27.4), which did not differ significantly between treatment groups.

Conclusions

Abiraterone, enzalutamide, cabazitaxel and docetaxel all demonstrate activity following progression on D‐ADT. No difference in efficacy was detected between treatment options for mCRPC. Prospective trials investigating the optimal treatment sequence for prostate cancer following progression on D‐ADT needed.
Long‐term survival and prognostic analysis of advanced stage follicular lymphoma in the rituximab era: A China single‐center retrospective study
Authors: Zhou Yu , Qin Yan , He Xiaohui , Liu Peng , Yang Jianliang , Zhou Liqiang , Zhou Shengyu , Gui Lin , Yang Sheng , Zhang Changgong , Shi Yuankai
Published: September 2020

Aim

The prognosis and treatment options for follicular lymphoma (FL) remain heterogenous. This study aimed to analyze the prognostic impact of rituximab maintenance and evaluate the prognostic models in Chinese FL patients.

Methods

We retrospectively evaluated patients with treatment‐naïve advanced stage FL who were treated in Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College between January 2008 and December 2018. We compared the baseline characteristics, long‐term survival outcomes, prognostic factors and the performance of four common prognostic models (i.e., FLIPI, FLIPI2, PRIMA‐PI and LDH+β2M) between them.

Results

A total of 158 patients were included (rituximab maintenance group, 77 patients; observation group, 81 patients). The median follow‐up time was 61.0 months. The rituximab maintenance group showed significantly higher 5‐year progression‐free survival (PFS; 83.3% vs 52.7%, P < 0.001) and overall survival (OS; 97.8% vs 84.1%, P = 0.032) than the observation group. FLIPI2 showed a more discriminating C index than the other three models.

Conclusion

This study showed that rituximab maintenance after chemoimmunotherapy induction can prolong both PFS and OS in patients with advanced‐stage FL, and FLIPI2 is a promising prognostic model.
Three‐dimensional ultrasonography for advanced neurosonography (neurosofe‐3D): Validation of a brain volume acquisition guideline
Authors: Maiz Nerea , Tajada Mauricio , Rodríguez María Á. , Irasarri Ana , Molina Francisca S. , Tubau Albert , Burgos Jorge , Alonso Ignacio , Plasencia Walter , Rodó Carlota , Pijoan José I. , Belar María , De Paco Matallana Catalina
Published: September 2020

Introduction

This study aimed to evaluate the quality of the brain volumes acquired following an evidence‐based guideline for the acquisition of brain volumes.

Material and methods

This was a prospective multicenter study. Five centers recruited five cases each, acquiring two volumes per case, at different gestational age ranges. From the collected volumes, 10 operators performed an advanced neurosonography of each case. The evaluable anatomic structures were counted in each volume and expressed as a percentage. The results were compared with those obtained in a previous study where no recommendations had been made for the acquisition of the volumes.

Results

Five hundred evaluations were included in the study. In the axial plane, 91.5% of the structures were satisfactorily evaluated, 81.8% in the coronal plane and 89.9% in the sagittal plane. These results were significantly better than those obtained in a previous study where the volumes had been acquired without any guidelines and the percentage of evaluable structures were 80% (P < .001), 67.1% (P < .001) and 55.1% (P < .001) in the axial, coronal and sagittal planes, respectively.

Conclusions

The application of an evidence‐based guideline for the acquisition of brain volumes improves the quality of these by increasing the number of evaluable structures in the volume.
Flying after left ventricular assist device implantation
Authors: Hanke Jasmin S. , Schmack Bastian , Merzah Ali Saad , Bounader Karl , Chatterjee Anamika , Mariani Silvia , Li Tong , Klautzsch Erik , Mueller Florian , Homann Katharina , Schoede Alexandra , Haverich Axel , Ruhparwar Arjang , Schmitto Jan D. , Dogan Günes
Published: September 2020

Literature on the air travel activities of patients supported by permanent mechanical assist devices is rare. To the best of our knowledge, no air travel guidelines or fitness prerequisites exist on whether and when ventricular assist device (VAD) patients are allowed to travel by plane after device implantation. In this study, we evaluated the topic of air travel after VAD implantation. This working group aimed to produce a report on air travel passengers supported by VADs, regarding their fitness to fly. Fifty left ventricular assist device (LVAD) patients were surveyed in a worldwide multicenter study. The single survey was performed with a multimethod design, including interviews conducted face‐to‐face, online, and on phone. Out of 50 patients, 97% described their traveling by aircraft as perfect and uneventful during the flight. Eighty‐five percent of the study participants consulted their medical practitioner before the flight. No patient reported the occurrence of a severe condition associated with flying. LVAD alarms, especially low flow alarms, did not occur in any of the devices. Thirty‐five percent of the surveyed patients, however, stated a major problem pertaining to the security check procedures at the airport. The results of this study suggest that commercial air travel is safe for stable patients on permanent VAD support and traveling can be resumed securely after VAD implantation. Conscientious preparation by packing necessary devices, fluids, medications, and careful preparation for the airport security check is recommended.
Stable incidence but regional differences in retinopathy of prematurity in Norway from 2009 to 2017
Authors: Grottenberg Beanca Gjølberg , Korseth Katinka Madtzog , Follestad Turid , Stensvold Hans Jørgen , Støen Ragnhild , Austeng Dordi
Published: September 2020

Purpose

To explore the changes over time and regional differences in the incidence of retinopathy of prematurity (ROP) in a national cohort of infants born <28 weeks' gestational age (GA).

Methods

A population‐based study of infants with GA <28 weeks in Norway from 2009 to 2017. Prospectively collected data on clinical variables and outcomes were obtained from the Norwegian Neonatal Network.

Results

Of 1499 live‐born infants transferred to a neonatal intensive care unit, 1156 were discharged alive. Four‐hundred and fifty‐eight infants (39.6%) had ROP, 152 (13.1%) had severe ROP, and 110 (9.5%) were treated for ROP. Eleven hundred infants (95.2%) had complete data sets. In a model comprising region of primary care, GA [odds ratios (OR): 0.65; 95% CI: 0.55–0.77], growth velocity (OR: 1.10; 95% CI: 1.00–2.00), medically treated patent ductus arteriosus (OR: 1.80; 95% CI: 1.19–2.72), weeks of supplemental oxygen (OR: 1.07; 95% CI: 1.03 to 1.11) and region of primary care (OR: 4.95; 95% CI: 3.05–8.04 for the pair of regions with the highest estimated OR) were significantly associated with severe ROP. Additionally, institutional differences for severe ROP were found, with ORs from 0.41 (95% CI: 0.05–3.23) to 5.36 (95% CI: 3.05–9.43) using the largest institution as reference. Incidences were stable over time after adjusting for GA. A larger proportion was treated with anti‐vascular endothelial growth factor after 2011.

Conclusions

The incidence of severe ROP was stable between 2009 and 2017 in Norway. Regional and institutional differences need to be explored in future studies.
Evaluating structural and compositional canopy characteristics to predict the light‐demand signature of the forest understorey in mixed, semi‐natural temperate forests
Authors: Depauw Leen , Perring Michael P. , Landuyt Dries , Maes Sybryn L. , Blondeel Haben , De Lombaerde Emiel , Brūmelis Guntis , Brunet Jörg , Closset‐Kopp Déborah , Decocq Guillaume , Den Ouden Jan , Härdtle Werner , Hédl Radim , Heinken Thilo , Heinrichs Steffi , Jaroszewicz Bogdan , Kopecký Martin , Liepiņa Ilze , Macek Martin , Máliš František , Schmidt Wolfgang , Smart Simon M. , Ujházy Karol , Wulf Monika , Verheyen Kris
Published: September 2020

Questions

Light availability at the forest floor affects many forest ecosystem processes, and is often quantified indirectly through easy‐to‐measure stand characteristics. We investigated how three such characteristics, basal area, canopy cover and canopy closure, were related to each other in structurally complex mixed forests. We also asked how well they can predict the light‐demand signature of the forest understorey (estimated as the mean Ellenberg indicator value for light [“EIVLIGHT”] and the proportion of “forest specialists” [“%FS”] within the plots). Furthermore, we asked whether accounting for the shade‐casting ability of individual canopy species could improve predictions of EIVLIGHT and %FS.

Location

A total of 192 study plots from nineteen temperate forest regions across Europe.

Methods

In each plot, we measured stand basal area (all stems >7.5 cm diameter), canopy closure (with a densiometer) and visually estimated the percentage cover of all plant species in the herb (<1 m), shrub (1–7 m) and tree layer (>7 m). We used linear mixed‐effect models to assess the relationships between basal area, canopy cover and canopy closure. We performed model comparisons, based on R2 and the Akaike Information Criterion (AIC), to assess which stand characteristics can predict EIVLIGHT and %FS best, and to assess whether canopy shade‐casting ability can significantly improve model fit.

Results

Canopy closure and cover were weakly related to each other, but showed no relation with basal area. For both EIVLIGHT and %FS, canopy cover was the best predictor. Including the share of high‐shade‐casting species in both the basal‐area and cover models improved the model fit for EIVLIGHT, but not for %FS.

Conclusions

The typically expected relationships between basal area, canopy cover and canopy closure were weak or even absent in structurally complex mixed forests. In these forests, easy‐to‐measure structural canopy characteristics were poor predictors of the understorey light‐demand signature, but accounting for compositional characteristics could improve predictions.
Comparative otolith morphology of clupeids from the Iranian brackish and marine resources (Teleostei: Clupeiformes)
Authors: Purrafee Dizaj Leyli , Esmaeili Hamid Reza , Teimori Azad
Published: September 2020

The diagnostic features of otolith morphology were provided for the clupeid fishes of the Iranian brackish and marine resources to be used as diagnostic features for the identification of clupeids diversity in these regions. Fish individuals belong to 20 species belong to 13 genera, and four families were collected from the Caspian Sea, the Persian Gulf and the Makran zone of the Oman Sea. Overall, seven otolith morphotypes were distinguished, that is lanceolated (45%), fusiform (20%), boot‐like (15%) and clamp‐like, pentagonal, elliptic and rectangular (each 5%, respectively). The univariate analysis showed that all variables except shape index [sulcus area (SS)/otolith area (OS)] and ROx (roundness) were significantly different among the clupeid species. The interspecific relationships of the otoliths were analysed based on the data of otolith morphology and otolith shape indices. Both dendrograms showed somehow an obvious separation among the studied species. However, the interspecific relationships in the dendrogram based on the otolith morphology have a better resolution. These phenotypic relationships based on otolith morphology among the studied clupeids are largely consistent with the previous hypothesis on the systematics of these fishes and emphasized that the morphological and morphometric features of the otolith, which are highlighted in this study, could be adequately used as diagnostic features for the identification of clupeids diversity.
Nonparametric cluster significance testing with reference to a unimodal null distribution
Authors: Helgeson Erika S. , Vock David M. , Bair Eric
Published: September 2020

Cluster analysis is an unsupervised learning strategy that is exceptionally useful for identifying homogeneous subgroups of observations in data sets of unknown structure. However, it is challenging to determine if the identified clusters represent truly distinct subgroups rather than noise. Existing approaches for addressing this problem tend to define clusters based on distributional assumptions, ignore the inherent correlation structure in the data, or are not suited for high‐dimension low‐sample size (HDLSS) settings. In this paper, we propose a novel method to evaluate the significance of identified clusters by comparing the explained variation due to the clustering from the original data to that produced by clustering a unimodal reference distribution that preserves the covariance structure in the data. The reference distribution is generated using kernel density estimation, and thus, does not require that the data follow a particular distribution. By utilizing sparse covariance estimation, the method is adapted for the HDLSS setting. The approach can be used to test the null hypothesis that the data cannot be partitioned into clusters and to determine the optimal number of clusters. Simulation examples, theoretical evaluations, and applications to temporomandibular disorder research and cancer microarray data illustrate the utility of the proposed method.
Adjuvant tyrosine kinase inhibitor therapy improves outcome for children and adolescents with acute lymphoblastic leukaemia who have an ABL‐class fusion
Authors: Moorman Anthony V. , Schwab Claire , Winterman Emily , Hancock Jerry , Castleton Anna , Cummins Michelle , Gibson Brenda , Goulden Nick , Kearns Pam , James Beki , Kirkwood Amy A. , Lancaster Donna , Madi Mabrouk , McMillan Andrew , Motwani Jayashree , Norton Alice , O’Marcaigh Aengus , Patrick Katharine , Bhatnagar Neha , Qureshi Amrana , Richardson Deborah , Stokley Simone , Taylor Gordon , van Delft Frederik W. , Moppett John , Harrison Christine J. , Samarasinghe Sujith , Vora Ajay
Published: September 2020

Patients with an ABL‐class fusion have a high risk of relapse on standard chemotherapy but are sensitive to tyrosine kinase inhibitors (TKI). In UKALL2011, we screened patients with post‐induction MRD ≥1% and positive patients (12%) received adjuvant TKI. As the intervention started during UKALL2011, not all eligible patients were screened prospectively. Retrospective screening of eligible patients allowed the outcome of equivalent ABL‐class patients who did and did not receive a TKI in first remission to be compared. ABL‐class patients who received a TKI in first remission had a reduced risk of relapse/refractory disease: 0% vs. 63% at four years (P = 0·009).
Narrative Matters: Adult anxieties and prejudice against children – childism in The Twilight Zone
Authors: Thomas Isaiah , Martin Andrés
Published: September 2020

Understanding the root causes of child mistreatment and abuse should be a key concern of child and adolescent psychiatrists. However, the issue is often framed in such a way that we fail to ask how and why child abuse happens. One framework for the psychosocial motivations behind child abuse is the concept of childism, or prejudice against children. A series such as The Twilight Zone can offer a means of exploring unhealthy adult‐child dynamics and applying the concept of childism to better understand them.
Parenting children who are enterally fed: How families go from surviving to thriving
Authors: Hopwood Nick , Elliot Chris , Moraby Khadeejah , Dadich Ann
Published: September 2020

Background

Complex feeding difficulties requiring enteral (tube) feeding affect everyone around the child. Parents experience additional stress and are at risk of social isolation. This study investigated the strategies families develop and use to adjust and adapt to enteral feeding so they were not just surviving but thriving as a family.

Methods

Twenty parents whose children had been or continued to be enterally fed were interviewed, four of them twice as their experience of enteral feeding progressed. Learning theory was used to conceptualize findings in terms of changing use of tools that mediated parents' response to feeding‐related challenges.

Results

Parents encountered dilemmas relating to enteral feeding: maintaining participation in everyday activities, managing responses to the use of tubes for feeding, and doing what feels right for their child. They used four kinds of mediating tools to overcome these: memory aids and readiness tools, metaphors and narratives, repurposed everyday objects and personalized routines and materialities.

Conclusions

This novel account of tool used to resolve dilemmas provides an empirically and theoretically grounded basis for supporting parents to thrive despite the challenges of enteral feeding. Specifically, it can guide information given to help parents anticipate and cope with dilemmas arising from enteral feeding.
Long‐termresults of implants and implant‐supportedprostheses under systematic supportive implant therapy: A retrospective25‐yearstudy
Authors: Frisch Eberhard , Wild Vanessa , Ratka‐Krüger Petra , Vach Kirstin , Sennhenn‐Kirchner Sabine
Published: September 2020

Background

Long‐term data (>10 years) concerning the survival and success rates of implants and implant‐supported prostheses are scarce.

Purpose

The present investigation represents one of the first studies on dental implants covering an observational period of 25 years.

Materials and methods

This study presents the results obtained in 26 patients with 75 implants who participated over a 23‐ to 28‐year period in a supportive implant therapy (SIT) program at a private dental practice. We extracted existing data from the patients' files (pocket depths [PDs], bleeding on probing [BoP], radiographic peri‐implant bone loss, and survival rates of the implant‐supported prostheses).

Results

After 25 years, the SIT‐compliant patients' implants had a survival rate of 95% (prostheses: 88%). The mean peri‐implant probing depth was 3.69 mm (median: 3.33; SD: 1.06; range: 2‐8.33). The mean peri‐implant bone level was 1.84 mm (median: 1.82; SD: 1.20; range: −0.97‐5.2). Finally, the prevalence (moment of last consultation) and incidence (during the entire observational period) of peri‐implantitis were 7% and 30%, respectively.

Conclusions

Under SIT conditions, clinicians may expect survival rates for implant‐supported prostheses of >80%. Most implants (60%) did not develop signs of peri‐implantitis over a 25‐year period.
Improved fuzzy‐assisted hierarchical neural network system for design of computer‐aided English teaching system
Authors: Li Hui
Published: September 2020

The world has enhanced the development of education with the rapid development of information technology in modern society to facilitate the information process. Educational technology has gained experience through the advancement of digital information network technology, from modern teaching technology to computer technology and communication technology. In this paper, an English learning system has been developed based on an improved fuzzy‐assisted hierarchical neural network system (IF‐HNNS). Improving the standard of English education is particularly important in improving intelligent education, especially the efficiency of classroom teaching. The development of an interactive educational system has changed the conventional way of teaching and facilitated individual independent learning. This English teaching system is a network updating computer‐aided learning platform. The computer‐aided system has the following advantages: (i) Easy‐to‐actualize computer‐aided learning media will provide more teaching content and teach satisfaction. (ii) The interaction of computer‐aided learning will raise interest in learning. (iii) Computer helped learners are rich in educational resources and are easy to set teaching goals. (iv) It will improve the monitoring of the education and teaching cycle using a computer‐aided learning with human‐computer interaction method.
“Taking action for the Reef?”–Australians do not connect Reef conservation with individual climate‐related actions
Authors: Dean Angela J. , Gulliver Robyn E. , Wilson Kerrie A.
Published: September 2020

Climate change is the most significant threat to the Great Barrier Reef (GBR). While Australians express appreciation and concern for the GBR, it is not clear whether they connect climate‐related action with reef conservation. An online survey of 4,285 Australians asked “…what types of actions could people like you do that would be helpful for the GBR?” Only 4.1% mentioned a specific action related to mitigating climate change; another 3.8% mentioned climate change but no specific action. The most common responses related to reducing plastic pollution (25.6%). These findings demonstrate that most Australians have poor capacity to identify individual climate‐related actions as helpful for reef protection, and that generic calls to action—such as “protect the reef”—are unlikely to elicit climate‐related actions. As such, reef conservation initiatives must explicitly promote actions—in the home and in society—that reduce emissions and support the transition to a low carbon society.
Collaborations between Clinical Pharmacologists in Japan and in the United States ‐ Report from the IQ CPLG and JPMA CPTF Meeting in Tokyo, Japan
Authors: Zhu Tong , Kayama Makoto , Girish Sandhya , Sinha Vikram , Bello Akintunde , Kawaguchi Atsuhiro , Czerniak Richard , Nagao Lee
Published: September 2020

The International Consortium for Innovation and Quality in Pharmaceutical Development (IQ) Clinical Pharmacology Leadership Group (CPLG) held its first meeting of Japan‐based representatives at Astellas Pharma headquarters in Tokyo on October 1, 2019. The meeting was also attended by Japan Pharmaceutical Manufactures Association (JPMA) Clinical Pharmacology Task Force (CPTF) members. Overall, nearly 30 clinical pharmacologists representing 14 companies attended the event. The meeting met its goal of enhancing mutual understanding of each organization’s activities. In a number of break‐out sessions, participants identified scientific topics for potential future collaboration between JPMA CPTF and IQ CPLG.
Modeling lay people’s ethical views on abortion: A Q‐methodology study
Authors: Hammami Muhammad , Hammami Rakad , Kawadry Suraya , Alvi Syed
Published: September 2020

Background

It isn’t clear how lay people balance the various ethical interests when addressing medical issues. We explored lay people’s ethical resolution models in relation to abortion.

Methods

In a tertiary healthcare setting, 196 respondents rank‐ordered 42 opinion‐statements on abortion following a 9‐category symmetrical distribution. Statements’ scores were analyzed by averaging‐analysis and Q‐methodology.

Results

Respondents’ mean (SD) age was 34.5(10.5) years, 53% were women, 68% Muslims (31% Christians), 28% Saudis (26% Filipinos), and 38% healthcare‐related. The most‐agreeable statements were “Acceptable if health‐benefit to woman large,” “Acceptable if congenital disease risk large,” and “Woman’s right if fetus has congenital disease.” The most‐disagreeable statements were “State’s right even if woman disagrees,” “Acceptable even with no congenital disease risk,” and “Father’s right even if woman disagrees.” Q‐methodology identified several resolution models that were multi‐principled, consequentialism‐dominated, and associated with respondents’ demographics. The majority of Christian women and men identified with and supported a relatively “fetus rights plus State authority‐oriented” model. The majority of Muslim women and men identified with and supported a “conception‐oriented” model and “consequentialism plus virtue‐oriented” model, respectively. One or more of three motives‐related statements received extreme ranks on averaging‐analysis and in 33% of the models.

Conclusions

1) On average, consequentialism, focusing on a woman’s health‐benefit and congenital disease risk, was the predominant approach. This was followed by the rights approach, favoring a woman’s interest but taking context into account. 2) Q‐methodology identified various ethical resolution models that were multi‐principled and partially associated with respondents’ demographics. 3) Motives were important to some respondents, providing empirical evidence against adequacy of principlism.
Project‐Based Learning for Teaching Business Analytics in the Undergraduate Curriculum*
Authors: Yazici Hulya Julie
Published: September 2020

The increasing use of massive data requires effective teaching strategies for business analytics. The discipline combines analytical skills, information technology, and business‐domain knowledge, and is challenging to teach to business students. This research demonstrates that business undergraduate students can benefit from an experiential project‐based learning approach (PjBL). By having student groups collecting data around a research question of their choosing and using descriptive and predictive analytics, we observed an increased understanding of the data‐driven decision‐making process, and improved analytical skills to approach, solve, and communicate business problems.
Inside the black box of youth participation and engagement: Development and implementation of an organization‐wide strategy for Orygen, a national youth mental health organization in Australia
Authors: Simmons Magenta B. , Fava Nicholas , Faliszewski Jacqui , Browne Vivienne , Chinnery Gina , van der El Kristi , Hodges Craig , Pennell Kerryn , Brushe Mary
Published: September 2020

Aim

The involvement of young people in the development, implementation and evaluation of youth mental health services, policy and research programs is essential to ensure they are appropriate and responsive to the needs of young people. Despite the increasingly central role that youth engagement and participation plays internationally, such activities are rarely described in detail. This article aims to provide a thorough description of the development and implementation of an organization‐wide, 3‐year Youth Engagement and Participation Strategy for Orygen, a national youth mental health organization in Australia.

Methods

A descriptive account of the development and implementation of the Strategy, with detailed examples of programs and initiatives.

Results

The Strategy was developed based on available evidence, focus groups with key stakeholders and best practice principles. The implementation of the Strategy resulted in a number of programs being delivered that involved a range of young people from across Australia. Despite being successful overall, a number of challenges were experienced. Ongoing considerations include ensuring diversity of partnerships, 'raising the bar' of youth participation and creating meaningful pathways.

Conclusions

Youth participation and engagement within a youth mental health context is best seen as an evolving ambition that must remain flexible to the needs of all stakeholders. Despite some challenges and ongoing fine‐tuning, it is possible to successfully implement youth participation and engagement across all areas of youth mental health, including service design and delivery, research and translation, and policy.
The academic profession in North Macedonia: A never ending transition
Authors: Spasovski Ognen , Pecakovska Suzana
Published: September 2020

The context of Macedonian higher education has changed dramatically in the last fifteen years. A rapid increase in the number of public and private institutions and a greater diversity of higher education degrees have not been associated with improvements in quality. The research output of academic staff is modest; academics contribute little to the society's development. Academia in North Macedonia is under pressure due to chronic underfinancing of higher education and research, and an underdeveloped system of quality assurance, as well as growing expectations for relevance and internationalisation. This article presents an original empirical study on academic staff. It examines how 388 faculty at higher education institutions in North Macedonia perceived changes in the environment of the academic profession, and how changes in their working conditions potentially influence their academic identity and wellbeing. The results are compared to European data. Findings show that about half of research participants believed that the overall conditions for work and the quality of teaching, learning and research have deteriorated in recent years. This contributes to a perception of the academic profession as stressful and unattractive which results in lower levels of overall academic wellbeing which constitutes a threat to academic identity amongst the staff. Consequently, we expect further decreases in motivation, work ethic and productivity in the academic profession, as well as an increase in the desire of academics to leave Macedonia.
Pioglitazone and statins lower incidence of Parkinson disease in patients with diabetes mellitus
Authors: Chang Y.‐Hu. , Yen S.‐J. , Chang Y.‐Ha. , Wu W.‐J. , Lin K.‐D.
Published: September 2020

Background and purpose

The pharmacologic effects of pioglitazone on the incidence of Parkinson disease (PD) are not clear. No study has examined the interaction between pioglitazone and statin treatment on prevention of PD. This study analyzed the associations between pioglitazone, statins, and the incidence of PD in patients with diabetes mellitus (DM) in Taiwan.

Methods

We used the National Health Insurance database from 1996 to 2013. DM and PD were diagnosed according to the International Classification of Diseases, Ninth Revision, Clinical Modification codes. We used the propensity score‐matching method to match the study groups. Cox regression analyses were employed to calculate the relative risk of the incidence of PD.

Results

There were 48 828 patients matched and categorized equally into the pioglitazone group and the non‐pioglitazone group. The number of PD patients in the pioglitazone group and the non‐pioglitazone group was 275 (1.1%) and 417 (1.7%), respectively. The pioglitazone group had a lower incidence of PD, with an adjusted hazard ratio (aHR) of 0.66 [95% confidence interval (CI): 0.57–0.78], and this benefit was dose‐dependent. Of note, as compared with either pioglitazone or statin treatment, our results first showed that the combination of pioglitazone and statins further lowered the risk of PD, with an aHR of 0.78 (95% CI: 0.64–0.94; P = 0.010).

Conclusions

Our study results suggested that pioglitazone could be a promising agent for reducing the incidence of PD in patients with DM, and works synergistically with statins.
Secondary forests offset less than 10% of deforestation‐mediated carbon emissions in the Brazilian Amazon
Authors: Smith Charlotte C. , Espírito‐Santo Fernando D. B. , Healey John R. , Young Paul J. , Lennox Gareth D. , Ferreira Joice , Barlow Jos
Published: September 2020

Secondary forests are increasing in the Brazilian Amazon and have been cited as an important mechanism for reducing net carbon emissions. However, our understanding of the contribution of secondary forests to the Amazonian carbon balance is incomplete, and it is unclear to what extent emissions from old‐growth deforestation have been offset by secondary forest growth. Using MapBiomas 3.1 and recently refined IPCC carbon sequestration estimates, we mapped the age and extent of secondary forests in the Brazilian Amazon and estimated their role in offsetting old‐growth deforestation emissions since 1985. We also assessed whether secondary forests in the Brazilian Amazon are growing in conditions favourable for carbon accumulation in relation to a suite of climatic, landscape and local factors. In 2017, the 129,361 km2 of secondary forest in the Brazilian Amazon stored 0.33 ± 0.05 billion Mg of above‐ground carbon but had offset just 9.37% of old‐growth emissions since 1985. However, we find that the majority of Brazilian secondary forests are situated in contexts that are less favourable for carbon accumulation than the biome average. Our results demonstrate that old‐growth forest loss remains the most important factor determining the carbon balance in the Brazilian Amazon. Understanding the implications of these findings will be essential for improving estimates of secondary forest carbon sequestration potential. More accurate quantification of secondary forest carbon stocks will support the production of appropriate management proposals that can efficiently harness the potential of secondary forests as a low‐cost, nature‐based tool for mitigating climate change.
What does the character of urban technology reveals about convergence versus divergence of innovation in China?—A technical lens to evaluate regional economic development
Authors: Chen Xiangdong , Lv Ping , Xue Shaofang , Li Ming
Published: September 2020

Regional technology characters (TCs) are studied in this paper to find whether innovation in Chinese cities leads to technology converging, or technology divergence, in both the intra‐city and inter‐city scales, with which regional economic development strength may be better explained. Based on a literature review on the subject, a two‐dimensional research framework and relevant technical lens are designed to clarify TC in cities composed of parameters on Technology Strength (TS) versus Technology Angle (TA). By applying Principle Component Analysis, a technical lens is made possible based on extracted parameters on three integrated technology dimensions for measuring TSs and TAs over 117 Chinese sample cities with invention patent data covering 21 technology field between 2005/2006 and 2015/2016. Technology convergence versus divergence are examined for 28/24 sample cities beyond average score, and the research findings indicate that technology divergence in Chinese cities can be confirmed at the inter‐city level, even partially at the intra‐city level. This finding holds for most sample cities with fairly large and modest TSs, while intra‐city technology converging is significant, especially for larger sized TS samples, however they also differ on different dimensions. This may imply that urban economic development in China is technical based and differentiated.
The detection of isochromosome i(12p) in malignant germ cell tumours and tumours with somatic malignant transformation by the use of quantitative real‐time polymerase chain reaction
Authors: Fichtner Alexander , Richter Annika , Filmar Simon , Gaisa Nadine T , Schweyer Stefan , Reis Henning , Nettersheim Daniel , Oing Christoph , Gayer Fabian A , Leha Andreas , Küffer Stefan , Ströbel Philipp , Kaulfuß Silke , Bremmer Felix
Published: September 2020

Aims

Malignant germ cell tumours (GCTs) of the testis are rare neoplasms, but the most common solid malignancies in young men. World Health Organization guidelines divide GCTs into five types, for which numerous immunohistochemical markers allow exact histological subtyping in the majority of cases. In contrast, a germ cell origin is often hard to prove in metastatic GCTs that have developed so‐called somatic malignant transformation. A high percentage, up to 89%, of GCTs are characterised by the appearance of isochromosome 12p [i(12p)]. Fluorescence in‐situ hybridisation has been the most common diagnostic method for the detection of i(12p) so far, but has the disadvantages of being time‐consuming, demanding, and not being a stand‐alone method. The aim of the present study was to establish a quantitative real‐time polymerase chain reaction assay as an independent method for detecting i(12p) and regional amplifications of the short arm of chromosome 12 by using DNA extracted from formalin‐fixed paraffin‐embedded tissue.

Methods and results

A cut‐off value to distinguish between the presence and absence of i(12p) was established in a control set consisting of 36 tumour‐free samples. In a training set of 149 GCT samples, i(12p) was detectable in 133 tumours (89%), but not in 16 tumours (11%). In a test set containing 27 primary and metastatic GCTs, all 16 tumours with metastatic spread and/or somatic malignant transformation were successfully identified by the detection of i(12p).

Conclusion

In summary, the qPCR assay presented here can help to identify, further characterise and assign a large proportion of histologically inconclusive malignancies to a GCT origin.
Integrative histopathological and immunophenotypical characterisation of the inflammatory microenvironment in spitzoid melanocytic neoplasms
Authors: Hillen Lisa M , Vandyck Hendrik L D , Leunissen Daphne J G , de Greef Bianca T A , Bosisio Francesca M , zur Hausen Axel , van den Oord Joost , Winnepenninckx Véronique
Published: September 2020

Aims

The role of inflammation in conventional cutaneous melanoma has been extensively studied, whereas only little is known about the inflammatory microenvironment and immunogenic properties of spitzoid melanocytic neoplasms. The composition of infiltrating immune cells and the architectural distribution of the inflammation, in particular, are still obscure. This is the first study, to our knowledge, to systematically characterise the inflammatory patterns and the leucocyte subsets in spitzoid melanocytic lesions.

Methods and results

We examined 79 spitzoid neoplasms including banal Spitz naevi (SN, n = 50), atypical Spitz tumours (AST, n = 17) and malignant Spitz tumours (MST, n = 12) using histopathological analysis and immunohistochemistry. Spitzoid melanocytic lesions showed a high frequency (67.1%, n = 53 of 79) of inflammation. Four inflammatory patterns were identified according to architectural composition, distribution and intensity of inflammation. The majority of the inflammatory infiltrate corresponded to CD3+/CD8+ T lymphocytes (56.1%), followed by CD3+/CD4+ T cells (35.7%) and CD68+ histiocytes (20.3%). CD3+/TIA‐1+ cytotoxic T lymphocytes constituted 3.7% of inflammatory cells. Rarely, CD3+/ granzyme B+ cytotoxic T lymphocytes (2.7%) and CD138+ plasma cells (0.5%) were detected in the infiltrating immune cells. There was no significant difference in the inflammatory cellular composition among the spitzoid melanocytic subgroups (SN versus AST versus MST).

Conclusion

Our findings demonstrate that Spitz tumours are highly immunogenic lesions. Inflammation with the presence of lymphocytic aggregates predominated in SN, but was not distinctive for this melanocytic category. A strong and intense inflammation was suggestive of an underlying malignancy. The infiltrating cytotoxic T lymphocyte subsets in Spitz tumours deserve further investigation in larger study cohorts to elucidate prognostic and immuno‐oncological therapeutic relevance.
Oral health perception and plight of patients of schizophrenia
Authors: Agarwal Deepali , Kumar Adarsh , B. C. Manjunath , Kumar Vijay , Sethi Sujata
Published: September 2020

Objective

To assess the oral health status, perception and dental treatment needs in patients of schizophrenia in the hospital set‐up in Rohtak district, Haryana.

Methods and result

A cross‐sectional study was conducted to assess the oral health in patients of schizophrenia at Postgraduate Institute of Medical Sciences, Rohtak, Haryana amongst patients with ≤48 score on BPRS. A modified Dental Coping Belief Scale along with a structured questionnaire and clinical examination were recorded. Descriptive and inferential statistics were used in relation to demographic variables. Amongst 111 subjects, 74.4% were males and the mean age was 34.73 ± 9.9 years. Around 77.5% had habit of regular mouth rinsing, 72% and 3% brushed their teeth once and twice daily, respectively. Subjects had high negative oral health beliefs and external locus of control for oral health. Compared to the general population, mean OHI (8.4 ± 2.5) and DMFT (3.09 ± 2.9) scores were higher. Nearly, 66% patients had gingival pockets and around 7% showed attachment loss above 3 mm or gingival recession.

Conclusion

Patients with schizophrenia have much poorer oral health as compared to general population. They are aware of their poor oral hygiene but are not motivated enough to take care of their oral health. A multifaceted approach is required to plan and undertake effective oral health preventive and rehabilitative measures for this special group.
Periprostatic fat thickness quantified by preoperative magnetic resonance imaging is an independent risk factor for upstaging from cT1/2 to pT3 in robot‐assisted radical prostatectomy
Authors: Iemura Yusuke , Hori Shunta , Tatsumi Yoshihiro , Fukui Shinji , Miyake Makito , Matsumura Yoshiaki , Kagebayashi Yoriaki , Samma Shoji , Fujimoto Kiyohide
Published: September 2020

Objectives

To analyze the correlation between periprostatic fat thickness on multiparametric magnetic resonance imaging and upstaging from cT1/2 to pT3 in robot‐assisted radical prostatectomy.

Methods

We retrospectively evaluated data from men with cT1/2 prostate cancer treated with robot‐assisted radical prostatectomy at Nara Prefecture General Medical Center, Nara, Japan, between March 2013 and December 2017. We calculated the periprostatic fat thickness and subcutaneous thickness from preoperative multiparametric magnetic resonance imaging. We divided the cohort into two groups for analysis. Group 1 included patients upstaged from clinical to pathological stage, whereas group 2 included those without upstaging.

Results

Data on 220 patients meeting the inclusion criteria were included in the analysis. A total of 36 patients were upstaged from clinical T1 or T2 to pathological T3, whereas 184 patients were not upstaged. The upstaging was associated with prostate volume, Gleason score, prostate‐specific antigen density, periprostatic fat thickness, Prostate Imaging Reporting and Data System score based on univariate analysis. Multivariate analysis showed prostate volume (P = 0.03, odds ratio 0.958, 95% confidence interval 0.921–0.996), Gleason score (P = 0.022, odds ratio 2.676, 95% confidence interval 1.153–6.213) and periprostatic fat thickness (P = 0.004, odds ratio 1.26, 95% confidence interval 1.079–1.471) as independent risk factors of upstaging.

Conclusions

Prostate volume, Gleason score and periprostatic fat thickness on multiparametric magnetic resonance imaging are significantly associated with and independent risk factors for upstaging from cT1/2 to pT3 in patients undergoing robot‐assisted radical prostatectomy.
Leader Location, Cooperation, and Coordination in Serial Supply Chains
Authors: Majumder Pranab , Srinivasan Ashok
Published: September 2020

In this paper, we study multi‐stage serial supply chains with price dependent deterministic demand and increasing marginal costs. We analyze the effect of contract leadership (i.e., the ability to offer wholesale price and two‐part tariff contracts) on supply chain performance and use that as a basis to study coordination and cooperation. There is strong evidence of first‐mover advantage in wholesale price contracting which is amplified when the chain is coordinated using two‐part tariff contracts We analyze cooperation and the implications of leader location in uncoordinated chains Our results demonstrate the importance of considering the entire sequence of successive contracts when assessing the performance of a supply chain. We find that in some cases an inefficient supply chain may have a natural tendency to reduce inefficiency through cooperation between non‐leader members
Immunomodulatory effects of berberine on the inflamed joint reveal new therapeutic targets for rheumatoid arthritis management
Authors: Shen Peng , Jiao Yang , Miao Li , Chen Ji‐hua , Momtazi‐Borojeni Amir Abbas
Published: September 2020

Rheumatoid arthritis (RA) is a chronic inflammatory syndrome designated by synovial joint inflammation leading to cartilage degradation and bone damage as well as progressive disability. Synovial inflammation is promoted through the infiltration of mononuclear immune cells, dominated by CD4+ T cells, macrophages and dendritic cells (DCs), together with fibroblast‐like synoviocytes (FLS), into the synovial compartment. Berberine is a bioactive isoquinoline alkaloid compound showing various pharmacological properties that are mainly attributed to immunomodulatory and anti‐inflammatory effects. Several lines of experimental study have recently investigated the therapeutic potential of berberine and its underlying mechanisms in treating RA condition. The present review aimed to clarify determinant cellular and molecular targets of berberine in RA and found that berberine through modulating several signalling pathways involved in the joint inflammation, including PI3K/Akt, Wnt1/β‐catenin, AMPK/lipogenesis and LPA/LPA1/ERK/p38 MAPK can inhibit inflammatory proliferation of FLS cells, suppress DC activation and modulate Th17/Treg balance and thus prevent cartilage and bone destruction. Importantly, these molecular targets may explore new therapeutic targets for RA treatment.
Resistance to natural and synthetic gene drive systems
Authors: Price Tom A. R. , Windbichler Nikolai , Unckless Robert L. , Sutter Andreas , Runge Jan‐Niklas , Ross Perran A. , Pomiankowski Andrew , Nuckolls Nicole L. , Montchamp‐Moreau Catherine , Mideo Nicole , Martin Oliver Y. , Manser Andri , Legros Mathieu , Larracuente Amanda M. , Holman Luke , Godwin John , Gemmell Neil , Courret Cécile , Buchman Anna , Barrett Luke G. , Lindholm Anna K.
Published: September 2020

Scientists are rapidly developing synthetic gene drive elements intended for release into natural populations. These are intended to control or eradicate disease vectors and pests, or to spread useful traits through wild populations for disease control or conservation purposes. However, a crucial problem for gene drives is the evolution of resistance against them, preventing their spread. Understanding the mechanisms by which populations might evolve resistance is essential for engineering effective gene drive systems. This review summarizes our current knowledge of drive resistance in both natural and synthetic gene drives. We explore how insights from naturally occurring and synthetic drive systems can be integrated to improve the design of gene drives, better predict the outcome of releases and understand genomic conflict in general.