bluuebunny/crossref_metadata_2025 huggingface dataset:
Systematic genetic testing for recessively inherited monogenic diabetes: a cross-sectional study in paediatric diabetes clinics
Authors: Patel Kashyap A. , Ozbek Mehmet N. , Yildiz Melek , Guran Tulay , Kocyigit Cemil , Acar Sezer , Siklar Zeynep , Atar Muge , Colclough Kevin , Houghton Jayne , Johnson Matthew B. , Ellard Sian , Flanagan Sarah E. , Cizmecioglu Filiz , Berberoglu Merih , Demir Korcan , Catli Gonul , Bas Serpil , Akcay Teoman , Demirbilek Huseyin , Weedon Michael N. , Hattersley Andrew T.
Published: October 2021

Aims/hypothesis

Current clinical guidelines for childhood-onset monogenic diabetes outside infancy are mainly focused on identifying and testing for dominantly inherited, predominantly MODY genes. There are no systematic studies of the recessively inherited causes of monogenic diabetes that are likely to be more common in populations with high rates of consanguinity. We aimed to determine the contribution of recessive causes of monogenic diabetes in paediatric diabetes clinics and to identify clinical criteria by which to select individuals for recessive monogenic diabetes testing.

Methods

We conducted a cross-sectional study of 1093 children from seven paediatric diabetes clinics across Turkey (a population with high rates of consanguinity). We undertook genetic testing of 50 known dominant and recessive causes of monogenic diabetes for 236 children at low risk of type 1 diabetes. As a comparison, we used monogenic diabetes cases from UK paediatric diabetes clinics (a population with low rates of consanguinity).

Results

Thirty-four children in the Turkish cohort had monogenic diabetes, equating to a minimal prevalence of 3.1%, similar to that in the UK cohort (p = 0.40). Forty-one per cent (14/34) had autosomal recessive causes in contrast to 1.6% (2/122) in the UK monogenic diabetes cohort (p < 0.0001). All conventional criteria for identifying monogenic diabetes (parental diabetes, not requiring insulin treatment, HbA1c ≤ 58 mmol/mol [≤7.5%] and a composite clinical probability of MODY >10%) assisted the identification of the dominant (all p ≤ 0.0003) but not recessive cases (all p ≥ 0.2) in Turkey. The presence of certain non-autoimmune extra-pancreatic features greatly assisted the identification of recessive (p < 0.0001, OR 66.9) but not dominant cases.

Conclusions/interpretation

Recessively inherited mutations are a common cause of monogenic diabetes in populations with high rates of consanguinity. Present MODY-focused genetic testing strategies do not identify affected individuals. To detect all cases of monogenic paediatric diabetes, it is crucial that recessive genes are included in genetic panels and that children are selected for testing if they have certain non-autoimmune extra-pancreatic features in addition to current criteria.

Graphical abstract
Deoxynivalenol induces apoptosis and autophagy in human prostate epithelial cells via PI3K/Akt signaling pathway
Authors: Kowalska Karolina , Kozieł Marta Justyna , Habrowska-Górczyńska Dominika Ewa , Urbanek Kinga Anna , Domińska Kamila , Piastowska-Ciesielska Agnieszka Wanda
Published: October 2021

Phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway is one of the most deregulated signaling pathway in prostate cancer. It controls basic processes in cells: cell proliferation and death. Any disturbances in the balance between cell death and survival might result in carcinogenesis. Deoxynivalenol (DON) is one of the most common mycotoxins, a toxic metabolites of fungi, present in our everyday diet and feed. Although previous studies reported DON to induce oxidative stress, modulate steroidogenesis, DNA damage and cell cycle modulation triggering together its toxicity, its effect on normal prostate epithelial cells is not known. The aim of the study was to evaluate the effect of DON on the apoptosis and autophagy in normal prostate epithelial cells via modulation of PI3K/Akt signaling pathway. The results showed that DON in a dose of 30 µM and 10 µM induces oxidative stress, DNA damage and cell cycle arrest in G2/M cell cycle phase. The higher concentration of DON induces apoptosis, whereas lower one autophagy in PNT1A cells, indicating that modulation of PI3K/Akt by DON results in the induction of autophagy triggering apoptosis in normal prostate epithelial cells.
Mapping covariance in brain FDG uptake to structural connectivity
Authors: Yakushev Igor , Ripp Isabelle , Wang Min , Savio Alex , Schutte Michael , Lizarraga Aldana , Bogdanovic Borjana , Diehl-Schmid Janine , Hedderich Dennis M. , Grimmer Timo , Shi Kuangyu
Published: October 2021

Purpose

Inter-subject covariance of regional 18F-fluorodeoxyglucose (FDG) PET measures (FDGcov) as proxy of brain connectivity has been gaining an increasing acceptance in the community. Yet, it is still unclear to what extent FDGcov is underlied by actual structural connectivity via white matter fiber tracts. In this study, we quantified the degree of spatial overlap between FDGcov and structural connectivity networks.

Methods

We retrospectively analyzed neuroimaging data from 303 subjects, both patients with suspected neurodegenerative disorders and healthy individuals. For each subject, structural magnetic resonance, diffusion tensor imaging, and FDG-PET data were available. The images were spatially normalized to a standard space and segmented into 62 anatomical regions using a probabilistic atlas. Sparse inverse covariance estimation was employed to estimate FDGcov. Structural connectivity was measured by streamline tractography through fiber assignment by continuous tracking.

Results

For the whole brain, 55% of detected connections were found to be convergent, i.e., present in both FDGcov and structural networks. This metric for random networks was significantly lower, i.e., 12%. Convergent were 80% of intralobe connections and only 30% of interhemispheric interlobe connections.

Conclusion

Structural connectivity via white matter fiber tracts is a relevant substrate of FDGcov, underlying around a half of connections at the whole brain level. Short-range white matter tracts appear to be a major substrate of intralobe FDGcov connections.
What non-pharmacological treatments do people with polymyalgia rheumatica try: results from the PMR Cohort Study
Authors: Weddell Jake , Hider Samantha L. , Mallen Christian D. , Muller Sara
Published: October 2021

Polymyalgia rheumatica (PMR) is common. The mainstay of treatment, glucocorticoids, are associated with significant adverse effects and many patients remain on high doses for a number of years. Little is known about the use of other, non-pharmacological therapies as adjuncts in PMR. The PMR Cohort Study is an inception cohort study of patients diagnosed with PMR in primary care. This analysis presents data on the use and perceived impact of non-pharmacological therapies from a long-term follow-up survey. Non-pharmacological treatments were classified as either diet, exercise, or complementary therapies. Results are presented as adjusted means, medians, and raw counts where appropriate. One hundred and ninety-seven participants completed the long-term follow-up questionnaire, of these 81 (41.1%) reported using non-pharmacological therapy. Fifty-seven people reported using a form of complementary therapy, 35 used exercise and 20 reported changing their diet. No individual non-pharmacological therapy appeared to be associated with long-term outcomes. The use of non-pharmacological therapies is common amongst PMR patients, despite the paucity of evidence supporting their use. This suggests that people perceive a need for treatment options in addition to standard glucocorticoid regimens. Further research is needed to understand patients’ aims when seeking additional treatments and to strengthen the evidence base for their use so that patients can be guided towards effective options.
Total-internal-reflection deflectometry for measuring small deflections of a fluid surface
Authors: Jain Utkarsh , Gauthier Anaïs , van der Meer Devaraj
Published: October 2021

We describe a method that uses total internal reflection at the water–air interface inside a large, transparent tank, to measure the interface’s deflections. Using this configuration, we obtain an optical set-up where the liquid surface acts as a deformable mirror. The set-up is shown to be extremely sensitive to very small disturbances of the reflecting water surface, which are detected by means of visualising the reflections of a reference pattern. When the water surface is deformed, it reflects a distorted image of the reference pattern, similar to a synthetic Schlieren set-up. The distortions of the pattern are analysed using a suitable image correlation method. The displacement fields thus obtained correlate to the local spatial gradients of the water surface. The gradient fields are integrated in a least-squares sense to obtain a full instantaneous reconstruction of the water surface. This method is particularly useful when a solid object is placed just above water surface, whose presence makes the liquid surface otherwise optically inaccessible.

Graphical abstract
Magnetosensation during re-learning walks in desert ants (Cataglyphis nodus)
Authors: Fleischmann Pauline N. , Grob Robin , Rössler Wolfgang
Published: October 2021

At the beginning of their foraging careers, Cataglyphis desert ants calibrate their compass systems and learn the visual panorama surrounding the nest entrance. For that, they perform well-structured initial learning walks. During rotational body movements (pirouettes), naïve ants (novices) gaze back to the nest entrance to memorize their way back to the nest. To align their gaze directions, they rely on the geomagnetic field as a compass cue. In contrast, experienced ants (foragers) use celestial compass cues for path integration during food search. If the panorama at the nest entrance is changed, foragers perform re-learning walks prior to heading out on new foraging excursions. Here, we show that initial learning walks and re-learning walks are structurally different. During re-learning walks, foragers circle around the nest entrance before leaving the nest area to search for food. During pirouettes, they do not gaze back to the nest entrance. In addition, foragers do not use the magnetic field as a compass cue to align their gaze directions during re-learning walk pirouettes. Nevertheless, magnetic alterations during re-learning walks under manipulated panoramic conditions induce changes in nest-directed views indicating that foragers are still magnetosensitive in a cue conflict situation.
Evaluation of precipitation indices in suites of dynamically and statistically downscaled regional climate models over Florida
Authors: Srivastava Abhishekh Kumar , Grotjahn Richard , Ullrich Paul Aaron , Zarzycki Colin
Published: October 2021

The present work evaluates historical precipitation and its indices defined by the Expert Team on Climate Change Detection and Indices (ETCCDI) in suites of dynamically and statistically downscaled regional climate models (RCMs) against NOAA’s Global Historical Climatology Network Daily (GHCN-Daily) dataset over Florida. The models examined here are: (1) nested RCMs involved in the North American CORDEX (NA-CORDEX) program, (2) variable resolution Community Earth System Models (VR-CESM), (3) Coupled Model Intercomparison Project phase 5 (CMIP5) models statistically downscaled using localized constructed analogs (LOCA) technique. To quantify observational uncertainty, three in situ-based (PRISM, Livneh, CPC) and three reanalysis (ERA5, MERRA2, NARR) datasets are also evaluated against the station data. The reanalyses and dynamically downscaled RCMs generally underestimate the magnitude of the monthly precipitation and the frequency of the extreme rainfall in summer. The models forced with CanESM2 miss the phase of the seasonality of extreme precipitation. All models and reanalyses severely underestimate both the mean and interannual variability of mean wet-day precipitation (SDII), consecutive dry days (CDD), and overestimate consecutive wet days (CWD). Metric analysis suggests large uncertainty across NA-CORDEX models. Both the LOCA and VR-CESM models perform better than the majority of models. Overall, RegCM4 and WRF models perform poorer than the median model performance. The performance uncertainty across models is comparable to that in the reanalyses. Specifically, NARR performs poorer than the median model performance in simulating the mean indices and MERRA2 performs worse than the majority of models in capturing the interannual variability of the indices.
Systematic review and meta-analysis of tumour microsatellite-instability status as a predictor of response to fluorouracil-based adjuvant chemotherapy in colorectal cancer
Authors: Aggarwal Nikhil , Quaglia Alberto , McPhail Mark J. W. , Monahan Kevin J.
Published: October 2021

Purpose

Colorectal cancer (CRC) can be classified according to the chromosomal-instability pathway (a microsatellite-stable (MSS) pathway) and the microsatellite-instability (MSI) pathway. Adjuvant therapy after surgery in advanced CRC is usually based on fluoropyrimidine 5-fluorouracil (5-FU) alone or combined with other agents. Controversy however remains on the use of 5-FU-based regimens in treating MSI-related tumours.

Aims

To systematically investigate the relationship between tumour microsatellite profile and 5-year overall survival in patients with CRC treated with 5-FU.

Methods

A systematic literature review of PubMed and Embase databases was conducted. Pre-specified criteria determined study inclusion/exclusion. The PRISMA and QUADAS-2 criteria were used to assess study suitability and quality respectively. Patients were categorised as having either MSI or MSS CRC. Overall 5-year survival was estimated from Kaplan–Meier curves. Publication bias was assessed using funnel-plots and Egger’s test.

Results

1807 studies were identified, with meta-analysis performed using nine studies. 5-FU treated individuals with CRC who died at 5 years were found to be 0.31 times less likely to have MSI than those who were alive, although this was not statistically significant. There was an insufficient number of studies to enable subgroup analysis by stage.

Conclusions

In this meta-analysis, MSI status does not alter 5-year survival of patients with CRC patients treated with adjuvant 5-FU, however there is significant heterogeneity in the design of individual studies in the data synthesis. More studies are necessary to clarify whether CRC patients with MSI CRC, in particular early stage, should be offered 5-FU based adjuvant chemotherapy.
Diagnostik und Therapie lokaler Wundinfektionen
Authors: Dissemond Joachim
Published: October 2021

Lokale Wundinfektionen sind ein multidisziplinär relevantes Problem und sollten möglichst frühzeitig diagnostiziert und adäquat therapiert werden. Neben einer Stagnation der Wundheilung sind es insbesondere die drohende Weiterentwicklung zu systemischen Infektionen bis hin zur Sepsis, die gefürchtete, potenziell lebensbedrohliche Komplikationen darstellen. Einen besonders hohen und multidisziplinären Stellenwert hat diese Thematik bei der Behandlung von Patienten mit chronischen Wunden. Bislang gab es für die Diagnostik keine einheitlich akzeptierten Kriterien. Hier ermöglicht jetzt der neu entwickelte und validierte TILI-Score als Ergänzung zu den Vitalparametern und serologischen Werten die rasche Objektivierung lokaler Wundinfektionen. Ergänzend können mit dem W.A.R.-Score zudem Patienten mit erhöhtem Infektionsrisiko identifiziert werden. Durch diese einfach einzusetzenden Hilfsmittel kann die Indikation einer antiseptischen Wundtherapie individuell, schnell und unproblematisch eingeschätzt werden. Für viele Patienten mit chronischen Wunden ist dann Polihexanid das Wundantiseptikum der ersten Wahl. Die Indikation von Wundantiseptika sollte aber spätestens nach einer Therapiedauer von 14 Tagen kritisch überprüft werden.
Boron Intake and decreased risk of mortality in kidney transplant recipients
Authors: Kremer Daan , Post Adrian , Seidel Ulrike , Huebbe Patricia , van der Veen Yvonne , Groothof Dion , Gomes-Neto António W. , Knobbe Tim J. , Lüersen Kai , Eisenga Michele F. , Navis Gerjan J. , Rimbach Gerald , Bakker Stephan J. L. ,   TransplantLines Investigators, Kremer D. , Knobbe T. J. , Annema-de Jong J. H. , Berger S. P. , Blokzijl J. , Bodewes F. A. J. A. , de Boer M. T. , Damman K. , De Borst M. H. , Diepstra A. , Dijkstra G. , Douwes R. M. , Eisenga M. F. , Erasmus M. E. , Gan C. T. , Gomes Neto A. W. , Grootjans H. , Hak E. , Heiner-Fokkema M. R. , Hepkema B. G. , Klont F. , Leuvenink H. G. D. , Lexmond W. S. , de Meijer V. E. , Niesters H. G. M. , van Pelt L. J. , Pol R. A. , Porte R. J. , Ranchor A. V. , Sanders J. S. F. , Schutten J. C. , Siebelink M. J. , Slart R. H. J. A. , Swarte J. C. , Timens W. , Touw D. J. , van den Heuvel M. C. , van Leer-Buter C. , van Londen M. , Verschuuren E. A. M. , Vos M. J. , Weersma R. K. , Bakker S. J. L.
Published: October 2021

Purpose

In a search for potentially modifiable factors to improve long-term outcome among kidney transplant recipients (KTR), we hypothesized that boron exposure is associated with improved long-term outcome in KTR.

Methods

We determined 24 h urinary boron excretion using inductively coupled plasma mass spectrometry as a measure of boron exposure in 693 stable KTR (57% male, mean age 53y), enrolled in the TransplantLines Food and Nutrition Biobank and Cohort Study. Dietary intake was assessed using validated food-frequency questionnaires.

Results

Linear regression analyses showed that dietary intake of fruit, wine and nuts were key determinants of boron excretion. In addition, boron excretion was negatively correlated with homocysteine and inflammatory parameters. In total, 73 (32%), 47 (20%) and 30 (13%) KTR died among the lowest, middle and highest tertiles of 24 h urinary boron excretion, respectively (Plog-rank < 0.001). Cox regression analyses showed that high boron excretion was strongly associated with lower risk of mortality, independent of age, sex, estimated glomerular filtration rate and history of cardiovascular disease (HR per doubling: 0.51, 95% CI: 0.40 to 0.66, P < 0.001).

Conclusion

Boron may be an overlooked target to improve long-term survival among KTR and potentially other patients, likely through pathways other than inflammation or the methionine-homocysteine cycle that were previously suggested. Interventional trials are warranted to confirm the potential of dietary boron supplementation in KTR and other patient populations.
Elongational viscosity and brittle fracture of bidisperse blends of a high and several low molar mass polystyrenes
Authors: Wagner Manfred H. , Narimissa Esmaeil , Shahid Taisir
Published: October 2021

Elongational viscosity data of four well-characterized blends consisting of 10% mass fraction of monodisperse polystyrene PS-820k (molar mass of 820 kg/mol) and 90% matrix polystyrenes with a molar mass of 8.8, 23, 34, and 73 kg/mol, respectively, as reported by Shahid et al. Macromolecules 52: 2521–2530, 2019 are analyzed by the extended interchain pressure (EIP) model including the effects of finite chain extensibility and filament rupture. Except for the linear-viscoelastic contribution of the matrix, the elongational viscosity of the blends is mainly determined by the high molar mass component PS-820k at elongation rates when no stretching of the lower molar mass matrix chains is expected. The stretching of the long chains is shown to be widely independent of the molar mass of the matrix reaching from non-entangled oligomeric styrene (8.8 kg/mol) to well-entangled polystyrene (73kg/mol). Quantitative agreement between data and model can be obtained when taking the interaction of the long chains of PS-820k with the shorter matrix chains of PS-23k, PS-34k, and PS-73k into account. The interaction of long and short chains leads to additional entanglements along the long chains of PS-820k, which slow down relaxation of the long chains, as clearly seen in the linear-viscoelastic behavior. According to the EIP model, an increased number of entanglements also lead to enhanced interchain pressure, which limits maximal stretch. The reduced maximal stretch of the long chains due to entanglements of long chains with shorter matrix chains is quantified by introducing an effective polymer fraction of the long chains, which increases with the increasing length of the matrix chains resulting in the excellent agreement of experimental data and model predictions.
Machine-learning-based top-view safety monitoring of ground workforce on complex industrial sites
Authors: Golcarenarenji Gelayol , Martinez-Alpiste Ignacio , Wang Qi , Alcaraz-Calero Jose Maria
Published: October 2021

Telescopic cranes are powerful lifting facilities employed in construction, transportation, manufacturing and other industries. Since the ground workforce cannot be aware of their surrounding environment during the current crane operations in busy and complex sites, accidents and even fatalities are not avoidable. Hence, deploying an automatic and accurate top-view human detection solution would make significant improvements to the health and safety of the workforce on such industrial operational sites. The proposed method (CraneNet) is a new machine learning empowered solution to increase the visibility of a crane operator in complex industrial operational environments while addressing the challenges of human detection from top-view on a resource-constrained small-form PC to meet the space constraint in the operator’s cabin. CraneNet consists of 4 modified ResBlock-D modules to fulfill the real-time requirements. To increase the accuracy of small humans at high altitudes which is crucial for this use-case, a PAN (Path Aggregation Network) was designed and added to the architecture. This enhances the structure of CraneNet by adding a bottom-up path to spread the low-level information. Furthermore, three output layers were employed in CraneNet to further improve the accuracy of small objects. Spatial Pyramid Pooling (SPP) was integrated at the end of the backbone stage which increases the receptive field of the backbone, thereby increasing the accuracy. The CraneNet has achieved 92.59% of accuracy at 19 FPS on a portable device. The proposed machine learning model has been trained with the Standford Drone Dataset and Visdrone 2019 to further show the efficacy of the smart crane approach. Consequently, the proposed system is able to detect people in complex industrial operational areas from a distance up to 50 meters between the camera and the person. This system is also applicable to the detection of any other objects from an overhead camera.
A fuzzy logic-based approach for evaluating forest ecosystem service provision and biodiversity applied to a case study landscape in Southern Germany
Authors: Biber Peter , Schwaiger Fabian , Poschenrieder Werner , Pretzsch Hans
Published: October 2021

In the field of assessing forest ecosystem service provision and biodiversity, there seems to be a gap between an existing large body of valuable expert knowledge and its application. We propose fuzzy logic evaluation systems as a contribution to closing that gap. With this method-focused pilot study, we explored the potential of fuzzy logic for assessing the provision of different ecosystem services in a simulation case study, covering a large forest landscape in Southern Germany. Based on expert knowledge and available literature, we designed a fuzzy logic evaluation system for biodiversity, and the ecosystem services balanced wood production, storm and bark beetle damage resistance, and recreation value. This evaluation system was applied to 100-year simulation outcomes for three contrasting forest management scenarios in the landscape of interest. While the results of the case study in general support the idea of a multifunctional forest management, fuzzy logic turned out pronouncedly useful as a method. This is due to its potential to make otherwise unused expert knowledge applicable and transparent in a formal evaluation process. Based on our results, we discuss the approach related to its potential for interdisciplinary integration of knowledge, for revealing tradeoffs and synergies, and participative planning processes.
Communicating climate change findings from IPCC reports: insights from outreach events in India
Authors: Pathak Minal , Roy Joyashree , Patel Shaurya , Some Shreya , Vyas Purvi , Das Nandini , Shukla Priyadarshi
Published: October 2021

In recent years, the Intergovernmental Panel on Climate Change (IPCC) has been collaborating with Indian institutions to organise outreach events. This essay draws on the perspective of participants, speakers and organisers of 17 in-person outreach events conducted across India in 2018 and 2020, to share insights and recommendations for future IPCC events in India and other developing country contexts. The formats analysed in this essay range from panel events with very large public audiences to more focused workshops, meetings and seminars. Target audiences covered both academic and non-academic audiences and included researchers, teachers, students, industry and NGOs. The events, while achieving their main objective of communicating the findings of IPCC reports, also provided a platform for open discussion of localised climate impacts and good practices in adaptation and mitigation. There are, however, notable challenges to public outreach in India, specifically in terms of attracting an adequate number of participants, experts’ availability, communicating to a diverse audience and translation into local languages. The biggest challenge faced by speakers was a lack of knowledge about the number of attendees and the composition of the audience prior to an event. It is our recommendation that future outreach events in India are designed to be interactive, tailored to the regional context and complemented by simplified communication materials. Speakers should be provided with audience information and background prior to the event, and greater reach into rural areas, including school children, could be achieved with material in local languages. Additionally, event organisers often require logistical and operational support to host outreach events.
The Soul of Therapy: The Therapist’s Use of Self in the Therapeutic Relationship
Authors: Aponte Harry Joseph
Published: October 2021

This paper is based on the premises that the conscious, active and purposeful use of self by the therapist in the therapeutic process is an essential aptitude in establishing an effective therapeutic relationship, and that this therapeutically purposeful use of self can and should be incorporated in the training of all therapists in a explicitly systematic manner. The paper will attempt to identify the contributions of the “what and how” the use of self by therapists contributes to the therapeutic process. First of all, therapists’ use of self is meant to be viewed as a Common Factor as defined by Sprenkle, Davis & Lebow (2009), which is a perspective about the effectiveness of therapy that “asserts that the qualities and capabilities of the person offering the treatment are more important than the treatment itself” (p. 4). Secondly, the use of self by therapists emphasizes developing the skill set of the therapist in the conscious, active and purposeful use of self as is in the moment of the therapeutic engagement with clients, and does so without denying the importance of therapists working to resolve personal issues of theirs that may interfere with the therapist's professional effectiveness. Therapists’ use of self gives particular emphasis to the purposeful use of self as is in therapy’s relationship, assessment and interventions whatever the therapy model (Aponte & Kissil, 2016). Thirdly, the use of self represents an aptitude that can be developed and refined through well elaborated structures for schooling therapists in the therapeutic use of all they bring of their personal selves to the therapy relationship including through the use of their human vulnerabilities as they exist at the moment of empathic engagement with clients.
Rapid emergence of boscalid resistance in Swedish populations of Alternaria solani revealed by a combination of field and laboratory experiments
Authors: Mostafanezhad Hadis , Edin Eva , Grenville-Briggs Laura J. , Lankinen Åsa , Liljeroth Erland
Published: October 2021

Early blight, caused by Alternaria solani, is a common potato disease worldwide. Reduced field efficacy of the fungicide boscalid against this disease has been reported in several countries. Boscalid resistance has been mostly studied with in-vitro and/or greenhouse experiments. Field studies validating this phenomenon are largely missing. Here, for the first time in Scandinavia, we validated boscalid resistance in a Swedish population of A. solani both in the field and in the laboratory. Field trials between 2014 and 2017 in Nymö showed significant efficacy reduction by year. The target regions of the A. solani genes encoding the succinate dehydrogenase subunits (Sdh) B, C and D of samples collected from Nymö, and additional fields in south-eastern and central Sweden, were analysed for substitutions associated with loss of boscalid sensitivity. In 2014, the SdhC-H134R mutation was found at several sites at a low frequency, while, in 2017, the majority of the samples had either the SdhB-H278Y or the SdhC-H134R substitution. No mutations were detected in the gene encoding the SdhD subunit. Spore germination tests showed a high sensitivity (EC50 < 1 μg mL−1) of isolates lacking the substitutions. This was supported by a significant decrease in their radial growth rate, from 0.1 to 10 μg mL−1 boscalid. However, the mutated isolates had EC50 > 100 μg mL−1 and their growth rates hardly decreased at concentrations above 1–10 μg mL−1. These results add to the current knowledge of fungicide resistance development in field and indicate that early blight management in southeast Sweden should no longer rely on boscalid.
GitHub Discussions: An exploratory study of early adoption
Authors: Hata Hideaki , Novielli Nicole , Baltes Sebastian , Kula Raula Gaikovina , Treude Christoph
Published: October 2021

Discussions is a new feature of GitHub for asking questions or discussing topics outside of specific Issues or Pull Requests. Before being available to all projects in December 2020, it had been tested on selected open source software projects. To understand how developers use this novel feature, how they perceive it, and how it impacts the development processes, we conducted a mixed-methods study based on early adopters of GitHub discussions from January until July 2020. We found that: (1) errors, unexpected behavior, and code reviews are prevalent discussion categories; (2) there is a positive relationship between project member involvement and discussion frequency; (3) developers consider GitHub Discussions useful but face the problem of topic duplication between Discussions and Issues; (4) Discussions play a crucial role in advancing the development of projects; and (5) positive sentiment in Discussions is more frequent than in Stack Overflow posts. Our findings are a first step towards data-informed guidance for using GitHub Discussions, opening up avenues for future work on this novel communication channel.
Longitudinal Stability of Intellectual Functioning in Autism Spectrum Disorder: From Age 3 Through Mid-adulthood
Authors: Prigge Molly B. D. , Bigler Erin D. , Lange Nicholas , Morgan Jubel , Froehlich Alyson , Freeman Abigail , Kellett Kristina , Kane Karen L. , King Carolyn K. , Taylor June , Dean Douglas C. , King Jace B. , Anderson Jeff S. , Zielinski Brandon A. , Alexander Andrew L. , Lainhart Janet E.
Published: October 2021

Intelligence (IQ) scores are used in educational and vocational planning for individuals with autism spectrum disorder (ASD) yet little is known about the stability of IQ throughout development. We examined longitudinal age-related IQ stability in 119 individuals with ASD (3–36 years of age at first visit) and 128 typically developing controls. Intelligence measures were collected over a 20-year period. In ASD, Full Scale (FSIQ) and Verbal (VIQ) Intelligence started lower in childhood and increased at a greater rate with age relative to the control group. By early adulthood, VIQ and working memory stabilized, whereas nonverbal and perceptual scores continued to change. Our results suggest that in individuals with ASD, IQ estimates may be dynamic in childhood and young adulthood.
Mobile, Socially Assistive Robots Incorporating Approach Behaviour: Requirements for Successful Dialogue with Dementia Patients in a Nursing Home
Authors: Nakamura Mio , Ikeda Kohei , Kawamura Kazuki , Nihei Misato
Published: October 2021

The purpose of this study was to determine the effectiveness of using a mobile socially assistive robot (SAR) that incorporates approach behaviour (APB) for seniors. The participants were 15 residents in a nursing home. The effectiveness of dialogue with participants was compared for two types of SARs: stationary and mobile. Interactions were also examined to determine the factors that led to the success or failure of the dialogue based on the trajectory of the mobile SARs and observations of the participants’ behaviour with the mobile SARs. The results showed that nine of 15 participants (60 %) engaged in dialogue with mobile SARs, which was twice as effective as stationary SARs. Conversely, some participants could not engage in dialogue when using a mobile SAR. In addition, these participants’ The Mini-Mental State Examination (MMSE) scores were low. These participants’ successful dialogues were influenced by the angle at which the mobile SAR approached the participant and the length of time the mobile SAR and the participant were face to face. In this study, it was shown that the introduction of mobile SARs in a nursing home could facilitate communication between SARs and residents and further contribute to the quality of life of residents.
Nonverbal Auditory Cues Allow Relationship Quality to be Inferred During Conversations
Authors: Dunbar R. I. M. , Robledo Juan-Pablo , Tamarit Ignacio , Cross Ian , Smith Emma
Published: October 2021

The claim that nonverbal cues provide more information than the linguistic content of a conversational exchange (the Mehrabian Conjecture) has been widely cited and equally widely disputed, mainly on methodological grounds. Most studies that have tested the Conjecture have used individual words or short phrases spoken by actors imitating emotions. While cue recognition is certainly important, speech evolved to manage interactions and relationships rather than simple information exchange. In a cross-cultural design, we tested participants’ ability to identify the quality of the interaction (rapport) in naturalistic third party conversations in their own and a less familiar language, using full auditory content versus audio clips whose verbal content has been digitally altered to differing extents. We found that, using nonverbal content alone, people are 75–90% as accurate as they are with full audio cues in identifying positive vs negative relationships, and 45–53% as accurate in identifying eight different relationship types. The results broadly support Mehrabian’s claim that a significant amount of information about others’ social relationships is conveyed in the nonverbal component of speech.
Experimental proof of thiophene hydrodesulfurization reaction steps by isotope (14C) labeled thiophene
Authors: Tétényi Pál , Szarvas Tibor , Ollár Tamás
Published: October 2021

Hydrodesulfurization of thiophene has been studied over alumina supported sulfided molybdena, nickel-promoted molybdena and over nickel (Mo, NiMo and Ni) catalysts. The experiments were carried out with a mixture of thiophene, labeled with radioactive carbon (thiophene-[G-]-14C) and of non-radioactive tetrahydrothiophene (1:1 mol ratio) in a micro catalytic system. It was established, that the main products were tetrahydrothiophene-14C, 1-butene-14C, 2-butene-14C, butane-14C. Tetrahydrothiophene-14C was a major intermediate in the conversion of thiophene—14C in the experimental condition applied. The amounts of converted tetrahydrothiophene on the catalysts were substantially higher than those of thiophene under the same conditions. Hydrothiophene and dihydrothiophene—14C were intermediate products in the hydrodesulfurization of thiophene and tetrahydrothiophene. The hydrodesulphurization of tetrahydrothiophene was paired with dehydrogenation, producing small amounts of thiophene. The experimental results have been considered in the discussion of the mechanism of thiophene and tetrahydrothiophene desulfurization reaction pathway.
Endogenous testosterone density as ratio of endogenous testosterone levels on prostate volume predicts tumor upgrading in low-risk prostate cancer
Authors: Porcaro Antonio Benito , Gallina Sebastian , Bianchi Alberto , Cerrato Clara , Tafuri Alessandro , Rizzetto Riccardo , Amigoni Nelia , Orlando Rossella , Serafin Emanuele , Gozzo Alessandra , Migliorini Filippo , Antoniolli Stefano Zecchini , Lacola Vincenzo , De Marco Vincenzo , Brunelli Matteo , Cerruto Maria Angela , Siracusano Salvatore , Antonelli Alessandro
Published: October 2021

Objectives

To evaluate preoperative endogenous testosterone (ET) density (ETD), defined as the ratio of ET on prostate volume, and tumor upgrading risk in low-risk prostate cancer (PCa).

Materials and methods

From November 2014 to December 2019, 172 low-risk patients had ET (nmol/L) measured. ETD, prostate-specific antigen density (PSAD) and the ratio of percentage of biopsy positive cores (BPC) to prostate volume (PV), defined as BPC density (BPCD), were evaluated. Associations with tumor upgrading in the surgical specimen were assessed by statistical methods.

Results

Overall, 121 patients (70.3%) had tumor upgrading, which was predicted by BPCD (odds ratio, OR = 4.640; 95% CI 1.903–11.316;p = 0.001; overall accuracy: 70.3%). On multivariate analysis, tumor upgrading and clinical density factors related to each other for BPCD being predicted by ETD (regression coefficient,b = 0.032; 95% CI 0.021–0.043;p < 0.0001), PSAD (b = 1.962; 95% CI 1.067–2.586;p < 0.0001) and tumor upgrading (b = 0.259; 95% CI 0.112–0.406;p = 0.001). According to the model, as BPCD increased, ETD and PSAD increased, but the increase was higher for upgraded cases who showed either higher tumor load but significantly lower mean levels of either ET or PSA.

Conclusions

As ETD increased, higher tumor loads were assessed; however, in upgraded patients, lower ET was also detected. ETD might stratify low-risk disease for tumor upgrading features.
Some pupils should know better (because there is better knowledge than opinion). Interim findings from an empirical study of pupils’ and teachers’ understandings of knowledge and big questions in Religious Education
Authors: Stones Alexis , Fraser-Pearce Jo
Published: October 2021

In this paper, we draw on interim findings of our research project on Religious Education (RE), knowledge and big questions. We have found Miranda Fricker’s concept of epistemic injustice useful in our analysis—that is, the notion that a person can be wronged “specifically in their capacity as a knower (Fricker 2007, 1). In interviews with Key Stage 3 pupils (aged 12–14) we found that for many pupils, their capacity to know was hindered by the prioritisation of respect for opinion. Where opinion is considered something not to be questioned, this seems to be a key indicator of epistemic disadvantage while some pupils valued and could employ criticality when considering knowledge claims (including opinions). Epistemic advantage in this way exacerbates epistemic injustice, broadening a gap between the epistemic haves and have-nots. This research is part of a larger project where we attempt to answer the question: ‘Does Religious Education have a distinctive contribution to make to the development of epistemic literacy?’. We begin with our account of epistemic literacy underpinned by Young’s powerful knowledge (Young and Muller 2010) and contextualise our data with discourses about knowledge and school education. We focus largely on the emergent theme of (respect for) opinions and we argue that the prioritisation of respect in RE is (for some pupils) a barrier to knowledge. We go on to explore why this matters for individuals, society and RE.
Hepatic hormone FGF21 and its analogues in clinical trials
Authors: Shao Weijuan , Jin Tianru
Published: October 2021

Fibroblast growth factor 21 (FGF21) is a fasting or stress inducible metabolic hormone produced mainly in the liver. It plays important roles in regulating both glucose and lipid homeostasis via interacting with a heterodimeric receptor complex comprising FGF receptor 1 (FGFR1) and β‐klotho (KLB). For the past decade, great effort has been made on developing FGF21 derivatives or specific FGF21 receptor agonists into therapeutic agents for various metabolic disorders including type 2 diabetes (T2D), obesity, and more importantly, nonalcoholic fatty liver disease (NAFLD). Here we have reviewed FGF21 gene and protein structures, its expression pattern, cellular signaling cascades that mediate FGF21 production and function. We have then summarized the six clinical trials utilizing four FGF21 analogues. Finally, two recent literatures on the development of GLP‐1 and FGF21 dual agonists were presented briefly.
Game Theory Basics
Authors: von Stengel Bernhard
Published: October 2021

Game theory is the science of interaction. This textbook, derived from courses taught by the author and developed over several years, is a comprehensive, straightforward introduction to the mathematics of non-cooperative games. It teaches what every game theorist should know: the important ideas and results on strategies, game trees, utility theory, imperfect information, and Nash equilibrium. The proofs of these results, in particular existence of an equilibrium via fixed points, and an elegant direct proof of the minimax theorem for zero-sum games, are presented in a self-contained, accessible way. This is complemented by chapters on combinatorial games like Go; and, it has introductions to algorithmic game theory, traffic games, and the geometry of two-player games. This detailed and lively text requires minimal mathematical background and includes many examples, exercises, and pictures. It is suitable for self-study or introductory courses in mathematics, computer science, or economics departments.
Rate of broad-spectrum antibiotic overuse in patients receiving outpatient parenteral antibiotic therapy (OPAT)
Authors: Brenon Jessa R. , Shulder Stephanie E. , Munsiff Sonal S. , Burgoyne Colleen M. , Nagel Angela K. , Pillinger Kelly E.
Published: October 2021

Broad-spectrum antibiotics with once-daily dosing are often chosen for outpatient parenteral antibiotic therapy (OPAT) due to convenience even when narrower-spectrum antibiotics are appropriate. At our institution, up to 50% of select broad-spectrum OPAT regimens had potential to be narrowed, highlighting the need to re-evaluate regimens for de-escalation prior to discharge.
Cost-effectiveness of carbapenem-resistant Enterobacteriaceae (CRE) surveillance in Maryland
Authors: Lin Gary , Tseng Katie K. , Gatalo Oliver , Martinez Diego A. , Hinson Jeremiah S. , Milstone Aaron M. , Levin Scott , Klein Eili ,   for the CDC Modeling Infectious Diseases in Healthcare Program
Published: October 2021

Objective:

We analyzed the efficacy, cost, and cost-effectiveness of predictive decision-support systems based on surveillance interventions to reduce the spread of carbapenem-resistant Enterobacteriaceae (CRE).

Design:

We developed a computational model that included patient movement between acute-care hospitals (ACHs), long-term care facilities (LTCFs), and communities to simulate the transmission and epidemiology of CRE. A comparative cost-effectiveness analysis was conducted on several surveillance strategies to detect asymptomatic CRE colonization, which included screening in ICUs at select or all hospitals, a statewide registry, or a combination of hospital screening and a statewide registry.

Setting:

We investigated 51 ACHs, 222 LTCFs, and skilled nursing facilities, and 464 ZIP codes in the state of Maryland.

Patients or participants:

The model was informed using 2013–2016 patient-mix data from the Maryland Health Services Cost Review Commission. This model included all patients that were admitted to an ACH.

Results:

On average, the implementation of a statewide CRE registry reduced annual CRE infections by 6.3% (18.8 cases). Policies of screening in select or all ICUs without a statewide registry had no significant impact on the incidence of CRE infections. Predictive algorithms, which identified any high-risk patient, reduced colonization incidence by an average of 1.2% (3.7 cases) without a registry and 7.0% (20.9 cases) with a registry. Implementation of the registry was estimated to save $572,000 statewide in averted infections per year.

Conclusions:

Although hospital-level surveillance provided minimal reductions in CRE infections, regional coordination with a statewide registry of CRE patients reduced infections and was cost-effective.
Changes of Precipitation‐Runoff Relationship Induced by Climate Variation in a Large Glaciated Basin of the Tibetan Plateau
Authors: Wang Jiarong , Chen Xi , Liu Jintao , Hu Qi
Published: October 2021

Climate warming on the cryosphere could change catchment precipitation‐runoff relation by additional water from glacier melting and more energy absorbed at the ground surface. These changes further alter the physical properties of the catchment. The combined effects of these changes on runoff are analyzed from upstream to downstream of the Yarlung‐Zangpo River (YR) basin in southeastern Tibetan Plateau using statistical methods and a modified Budyko equation with consideration of glacier melting. Major results show that in the study period of 1980–2015 there was a jump in the mean annual temperature and precipitation around 1997. Since 1997, accelerated glacier melt and the thaw of permafrost have contributed to a nearly 80.9% increase in surface runoff in the upstream region of the YR basin. Meanwhile, the increase of runoff in the same period in downstream areas of the basin with warm and wet climates is smaller and has been mostly from an increase in annual precipitation. Part of that increase is offset by changes in catchment properties following the warming, such as the increase in vegetation coverage. Results of runoff responses to climate change and catchment properties across different sub‐basins in the YR basin and between the two time periods separated in 1997 suggest that continued warming would reduce the buffering effect of glacial and permafrost on runoff in upstream areas of the basin, shortening the runoff response time to precipitation and increasing flood and drought vulnerability of the YR basin.