bluuebunny/crossref_metadata_2025 huggingface dataset:
Quantenphysik in der Schule – Was benötigen Lehrkräfte? Ergebnisse einer Delphi-Studie
Authors: Weber Kim-Alessandro , Friege Gunnar , Scholz Rüdiger
Published: October 2020

Das Themengebiet Quantenphysik gilt als gleichermaßen bedeutend wie herausfordernd für den Physikunterricht in der Schule. Die Erzeugung einer empirischen Basis für die Konstruktion von Leitlinien für eine im besonderen Maße adressatenspezifische Lehrerfortbildung zum Thema Quantenphysik ist Gegenstand dieses Beitrags.

Die Didaktische Rekonstruktion zur Erarbeitung von Leitlinien für Lehrerfortbildungen leitet die vorgestellte Untersuchung. Basis der Rekonstruktion bilden die Analyse von bestehenden Konzepten zum Quantenphysikunterricht in der Schule und die empirische Erhebung von Sichtweisen der Lehrenden auf diese. Der Fokus liegt in diesem Beitrag auf der Erhebung und Auswertung der Sichtweisen von Lehrenden. Zu diesem Zweck wurde eine iterative Kommunikationstechnik zur Erhebung und Quantifizierung von Expertenmeinungen verwendet, die Delphi-Methode, welche in der fachdidaktischen Forschung etabliert ist.

Als Ergebnis der Didaktischen Rekonstruktion werden sechs Leitlinien vorgestellt, die Dozenten bei der Planung und Durchführung der Fortbildung unterstützen. Die Leitlinien implizieren eine Fortbildung, die den Weg von der klassischen zur Quantenphysik beschreitet und dabei Schlüsselexperimente in das Zentrum stellt.
EuGMS 2019 Congress report: evidence-based medicine in geriatrics
Authors: Hope Suzy V. , Koutsouri Anastasia , Nguyen Sylvain , Piotrowicz Karolina , Petrovic Mirko , Gasowski Jerzy
Published: October 2020

The 2019 EuGMS Congress “Evidence-Based Medicine in Geriatrics” was held in Krakow, Poland, and attended by over 1600 participants from 64 different countries. A summary and reflection on the congress was presented in the Closing Ceremony by European Academy for Medicine of Aging graduates, and summarised in this article. Keynote lectures, ‘state of the art’ sessions and symposia presented the evidence relating to different age-related conditions, their prevention, management and treatments. Hot topic areas included frailty and multimorbidity, and evidence-based attempts to address these conditions at different life stages. The field of geriatrics represents unique challenges for evidence-based medicine practice. There is much research going on. Clear leadership is needed to facilitate consensus agreements on standard definitions, methods and relevant outcomes, in collaboration with older people themselves, to maximise the opportunities and benefits of doing this research, and benefiting our patients and society at large.
Ion-Exchange Modeling of Monovalent Alkali Cation Adsorption on Montmorillonite
Authors: Li Yayu W. , Schulthess Cristian P.
Published: October 2020

Ion-exchange modeling is one of the most widely used methods to predict ion adsorption data on clay minerals. The model parameters (e.g. number of adsorption sites and the cation adsorption capacity of each site) are optimized normally by curve fitting experimental data, which does not definitively identify the local environment of the adsorption sites. A new approach for constructing an ion-exchange model was pursued, whereby some of the parameters needed were obtained independently, resulting in fewer parameters being based on data-curve fitting. Specifically, a reversed modeling approach was taken in which the number of types of sites used by the model was based on a previous first-principles Density Functional Theory study, and the relative distribution of these sites was based on the clay’s chemical composition. To simplify the ion-exchange reactions involved, montmorillonite was Na-saturated to produce a well-controlled Na-montmorillonite (NaMnt) adsorbent. Ion adsorption data on NaMnt were collected from batch experiments over a wide range of pH, Cs+ concentrations, and in the presence of coexisting cations. Ion-exchange models were developed and optimized to predict these cation adsorption data on NaMnt. The maximum amount of adsorption of monovalent cations on NaMnt was obtained from the plateau of the adsorption envelope data at high pH. The remaining equilibrium constants (pK) were optimized by curve fitting the edges of the adsorption envelope data. The resultant three-site ion-exchange model was able to predict the retention of Li+, Na+, K+, and Cs+ very well as a function of pH. The model was then tested on adsorption envelopes of various combinations of these cations, and on Cs+ adsorption isotherms at three different pH values. The pK values were constant for all assays. The interlayer spacing of NaMnt was also analyzed to investigate its relation with cation adsorption strength. An X-ray diffraction study of the samples showed that the measured d001 values for these cations were consistent with their adsorption pK values. The Cs+ cation showed a strong ability to collapse the interlayer region of montmorillonite. In the presence of multiple competing cations, the broadening and presence of multiple d001 XRD peaks suggested that the cations in the interlayers may be segregated.
Does Industry Timing Ability of Hedge Funds Predict Their Future Performance, Survival, and Fund Flows?
Authors: Bali Turan G. , Brown Stephen J. , Caglayan Mustafa O. , Celiker Umut
Published: October 2020

This paper investigates hedge funds’ ability to time industry-specific returns and shows that funds’ timing ability in the manufacturing industry improves their future performance, probability of survival, and ability to attract more capital. The results indicate that the best industry-timing hedge funds in the manufacturing sector have the highest return exposure to earnings surprises. This, together with persistently sticky earnings surprises, transparent information environment in regards to earnings releases, and large post-earnings-announcement drift in the manufacturing industry, explain to a great extent why best-timing hedge funds can generate significantly larger future returns compared to worst-timing hedge funds.
Recurrence rates in stable bipolar disorder patients after drug discontinuation v. drug maintenance: a systematic review and meta-analysis
Authors: Kishi Taro , Matsuda Yuki , Sakuma Kenji , Okuya Makoto , Mishima Kazuo , Iwata Nakao
Published: October 2020

Background

This random-effects model meta-analysis of double-blind, randomized placebo-controlled trials compared recurrence rates in bipolar disorder (BD) patients between antipsychotic/mood stabilizer discontinuation and maintenance groups.

Methods

We conducted systematic literature search of Embase, PubMed, and CENTRAL databases without language restriction from inception until 22 May 2020. Independent investigators assessed studies and extracted data. We calculated risk ratios (RRs) and numbers needed to benefit or harm (NNTB/NNTH). Primary outcome was the recurrence rate of any mood episode at 6 months. Secondary outcomes were recurrence rates of depressive episodes and manic/hypomanic/mixed episodes and all-cause discontinuation at 6 months. We also investigated these outcomes at 1, 3, 9, 12, 18, and 24 months.

Results

We identified 22 studies (n = 5462) receiving aripiprazole, asenapine, divalproex, long-acting injectable (LAI)-aripiprazole, LAI-risperidone, lamotrigine, lithium, olanzapine, paliperidone, or quetiapine. Mean study duration was 64.50 ± 69.35 weeks. The maintenance group demonstrated lower recurrence rates of any mood episode, depressive episodes, and manic/hypomanic/mixed episodes as well as reduced all-cause discontinuation at every observational point. The RRs (95% confidence interval, NNTB/NNTH) of recurrence rate at 6 months were 0.61 (0.54–0.70, 5) for any mood episode, 0.72 (0.60–0.87, 13) for depressive episodes, and 0.45 (0.36–0.57, 6) for manic/hypomanic/mixed episodes. The RR for all-cause discontinuation at 6 months was 0.71 (0.61–0.82, 6).

Conclusions

Maintaining drug treatment during clinically stable BD prevented recurrence for up to 24 months. Discontinuation of medications for ⩾1 month significantly increased recurrence risk. However, 47.3% of patients who discontinued drugs for 6 months did not experience recurrence.
A replication study of JTC bias, genetic liability for psychosis and delusional ideation
Authors: Henquet Cécile , van Os Jim , Pries Lotta K. , Rauschenberg Christian , Delespaul Philippe , Kenis Gunter , Luykx Jurjen J. , Lin Bochao D. , Richards Alexander L. , Akdede Berna , Binbay Tolga , Altınyazar Vesile , Yalınçetin Berna , Gümüş-Akay Güvem , Cihan Burçin , Soygür Haldun , Ulaş Halis , Cankurtaran Eylem S. , Kaymak Semra U. , Mihaljevic Marina M. , Petrovic Sanja S. , Mirjanic Tijana , Bernardo Miguel , Mezquida Gisela , Amoretti Silvia , Bobes Julio , Saiz Pilar A. , García-Portilla Maria P. , Sanjuan Julio , Aguilar Eduardo J. , Santos Jose L. , Jiménez-López Estela , Arrojo Manuel , Carracedo Angel , López Gonzalo , González-Peñas Javier , Parellada Mara , Maric Nadja P. , Atbaşoğlu Cem , Ucok Alp , Alptekin Köksal , Saka Meram C. , Arango Celso , O'Donovan Michael , Rutten Bart P.F. , Gülöksüz Sinan
Published: October 2020

Background

This study attempted to replicate whether a bias in probabilistic reasoning, or ‘jumping to conclusions’(JTC) bias is associated with being a sibling of a patient with schizophrenia spectrum disorder; and if so, whether this association is contingent on subthreshold delusional ideation.

Methods

Data were derived from the EUGEI project, a 25-centre, 15-country effort to study psychosis spectrum disorder. The current analyses included 1261 patients with schizophrenia spectrum disorder, 1282 siblings of patients and 1525 healthy comparison subjects, recruited in Spain (five centres), Turkey (three centres) and Serbia (one centre). The beads task was used to assess JTC bias. Lifetime experience of delusional ideation and hallucinatory experiences was assessed using the Community Assessment of Psychic Experiences. General cognitive abilities were taken into account in the analyses.

Results

JTC bias was positively associated not only with patient status but also with sibling status [adjusted relative risk (aRR) ratio : 4.23 CI 95% 3.46–5.17 for siblings and aRR: 5.07 CI 95% 4.13–6.23 for patients]. The association between JTC bias and sibling status was stronger in those with higher levels of delusional ideation (aRR interaction in siblings: 3.77 CI 95% 1.67–8.51, and in patients: 2.15 CI 95% 0.94–4.92). The association between JTC bias and sibling status was not stronger in those with higher levels of hallucinatory experiences.

Conclusions

These findings replicate earlier findings that JTC bias is associated with familial liability for psychosis and that this is contingent on the degree of delusional ideation but not hallucinations.
Exploring the efficacy of music in palliative care: A scoping review
Authors: Nyashanu Mathew , Ikhile Deborah , Pfende Farai
Published: October 2020

Objective

There is an increasing recognition of the significance of music as a complementary therapy in palliative care. Limited studies exist on how music is used as a coping mechanism by palliative care patients. Therefore, the purpose of this scoping review was to explore the efficacy of music interventions for palliative care.

Method

We conducted a literature search between June and November 2019 in the Cumulative Index of Nursing and Allied Health Literature (CINAHL), British Nursing Index (BNI), and PubMed, which includes MEDLINE. The search identified eight articles which met the inclusion and exclusion criteria.

Results

Using thematic analysis, six themes were synthesied to show how music contributes to palliative care. The six themes include Pain management; Relaxation; Happiness and hope; Anxiety and depression management; Enhanced spirituality; and Improved quality of life. These themes reflect the psychological and emotional benefits palliative care patients derive from music therapies.

Significance of results

Music therapy can be an effective psychosocial approach when managing palliative symptoms through its therapeutic effects on physical, psychological, emotional, and spiritual well-being.
Examples of Anglican Ritualism in Victorian South Africa: Towards an Understanding of Local Developments and Practice
Authors: Bethke Andrew-John
Published: October 2020

This article examines South Africa’s contribution to the spread of Anglican ritualism in the mid-nineteenth century and seeks to add a South African voice to the growing contemporary scholarship in this area. It begins by examining the role of South Africa’s first Anglican bishop in fostering a climate conducive to ritualism. This is followed by an examination of some of the early developments which were considered ‘popish’ by colonist congregations. The second part of the study focuses on two examples of advanced ritualist parishes paying attention to ‘signs’ of medievalist revivals and the confident manner in which ritualism was discussed. The author finds that after an initial period of fairly robust antagonism towards ritualism by colonists, a general movement towards ritualist practices began to emerge. The sources consulted for this article include letters, newspaper and periodical articles, archival material and a couple of unpublished theses.
Projections of Mountain Snowpack Loss for Wolverine Denning Elevations in the Rocky Mountains
Authors: Barsugli Joseph J. , Ray Andrea J. , Livneh Ben , Dewes Candida F. , Heldmyer Aaron , Rangwala Imtiaz , Guinotte John M. , Torbit Stephen
Published: October 2020

Future reduction in mountain snowpack due to anthropogenic climate change poses a threat to many snow‐adapted species worldwide. Mountain topography exerts a strong control on snowpack not only due to elevation but also through the effect of slope and aspect on the surface energy balance. We develop high‐resolution projections of snowpack in order to provide improved, physically based estimates of the spatial distribution of future snowpack to inform species conservation efforts for the wolverine (Gulo gulo) in two study areas in the Rocky Mountains: one in Montana with known den sites and one in Colorado with recent wolverine activity and potential for reintroduction. Here we assess springtime snowpack loss in actual and potential denning areas under five future climate scenarios for the mid‐21st century. Snowpack in April and May is likely to persist into the mid‐21st century in the upper half of current denning elevations in all but the warmest future climate scenario, while large declines are projected for the lower half of the denning elevations. We gain new insight into the influence of topographical aspect on future snowpack and quantify the potential for enhanced snow persistence on north and east facing slopes under future scenarios that is only revealed in simulations where terrain slopes are resolved.
Influential Climate Teleconnections for Spatiotemporal Precipitation Variability in the Lancang‐Mekong River Basin From 1952 to 2015
Authors: Irannezhad Masoud , Liu Junguo , Chen Deliang
Published: October 2020

The Lancang‐Mekong River Basin (LMRB) in Mainland Southeast Asia is home to ~70 million people, mostly living in poverty and typically working in primary freshwater‐related sectors, particularly agriculture and fishery. Understanding the mechanisms of the historical variability in precipitation (as the crucial water source) plays a key role in regional sustainable development throughout the LMRB. Herein, the spatiotemporal variability in interannual and intra‐annual precipitation over the LMRB was analyzed using the Global Precipitation Climatology Centre (GPCC) data for the period 1952–2015. The empirical orthogonal function (EOF) and wavelet transform coherence methods were utilized to investigate the relationships of such historical variations in annual (water year: November–October), dry season (November–May), and wet season (June–October) precipitation with 13 different climate teleconnections (eight large‐scale oceanic‐atmospheric circulation patterns and five summer monsoons). On the basin scale, only a significant (p < 0.05) wetting trend in the dry season precipitation (DSP) was uncovered. Spatially, significant wetting (drying) trends in annual precipitation detected over the northeastern (most western) parts of the Mekong River Basin during the water years 1952–2015, largely contributed by the substantial increases (decreases) in historical wet season precipitation. The most important precipitation pattern (EOF1) was identified as a strong (relatively weak) positive center in the eastern (southwestern) Mekong River Basin accompanying by a significantly high (relatively low) positive value for the first EOF mode of the dry season precipitation (wet season precipitation). Precipitation variability in the LMRB was significantly associated with the South Asian Summer Monsoon Index, Southern Oscillation Index, and Indian Summer Monsoon Index.
Quantifying and Numerically Representing Recharge and Flow Components in a Karstified Carbonate Aquifer
Authors: Schuler P. , Duran L. , Johnston P. , Gill L.
Published: October 2020

Karstified carbonate aquifers are highly heterogeneous systems characterized by multiple recharge, flow, and discharge components. The quantification of the relative contribution of these components, as well as their numerical representation, remains a challenge. This paper identifies three recharge components in the time and frequency domain. While the analysis in the time domain follows traditional approaches, the analysis of the power spectrum allows frequencies associated with specific spectral coefficients and noise types to be distinguished more objectively. The analysis follows the presented hypothesis that the different frequency‐noise components are the result of aquifer heterogeneity transforming the random rainfall input into a sequence of non‐Gaussian signals. The distinct signals are then numerically represented in the context of a semidistributed pipe network model in order to simulate recharge, flow, and discharge of an Irish karst catchment more realistically. By linking the power spectra of the modeled recharge components with the spectra of the spring discharge, the information usually gained by classical performance indicators is significantly widened. The modeled spring discharge is well matched in the time and frequency domain, yet the different recharge dynamics explain the signal of the aquifer outlet in different noise domains across the spectrum. This study demonstrates the conjunctive use of frequency analysis in conceptualization of a hydrological system together with modeling and evaluation.
Assessing and Managing Large‐Scale Geochemical Impacts From Groundwater Replenishment With Highly Treated Reclaimed Wastewater
Authors: Sun Jing , Donn Michael J. , Gerber Philippe , Higginson Simon , Siade Adam J. , Schafer David , Seibert Simone , Prommer Henning
Published: October 2020

Reuse of wastewater through a combination of advanced wastewater treatment (AWT) and managed aquifer recharge (MAR) is an important water management option. As an integral part of any AWT‐MAR system, the geochemical compatibility of the recharged water with the targeted aquifer must be assessed to avoid groundwater quality deterioration. Although short‐term field experiments may uncover potentially concerning sediment‐water disequilibria, an advanced analysis is often required to understand the long‐term geochemical impacts of large‐scale MAR. Here, we develop and apply a pragmatic approach to upscale and verify the previously derived local‐scale geochemical understanding to the spatial and temporal scale required for assessing and managing large‐scale and long‐term impacts resulting from the recharge of AWT‐processed water. We use Australia's largest MAR scheme, in which aerobic, purified water is injected into deep, anaerobic, pyritic aquifers as an illustrative example. In this case, the local‐scale understanding was derived from a comprehensive field trial and the interpretation of the data through a trial‐scale high‐resolution reactive transport model (RTM). Based on (i) the trial‐scale RTM, (ii) new data from the early phase of the full‐scale MAR, and (iii) downscaling of an existing, regional‐scale flow model, we developed an upscaled RTM to assess two critical issues for the large‐scale groundwater replenishment of Perth deep aquifers, that is, the sustainability of native pH buffering processes and the dynamics of fluoride release and attenuation. In a final step we illustrate how the upscaled RTM can be applied to assess how changes in the AWT affect long‐term groundwater pH changes.
The role of TDP-43 propagation in neurodegenerative diseases: integrating insights from clinical and experimental studies
Authors: Jo Myungjin , Lee Shinrye , Jeon Yu-Mi , Kim Seyeon , Kwon Younghwi , Kim Hyung-Jun
Published: October 2020

TAR DNA-binding protein 43 (TDP-43) is a highly conserved nuclear RNA/DNA-binding protein involved in the regulation of RNA processing. The accumulation of TDP-43 aggregates in the central nervous system is a common feature of many neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), Alzheimer’s disease (AD), and limbic predominant age-related TDP-43 encephalopathy (LATE). Accumulating evidence suggests that prion-like spreading of aberrant protein aggregates composed of tau, amyloid-β, and α-synuclein is involved in the progression of neurodegenerative diseases such as AD and PD. Similar to those of prion-like proteins, pathological aggregates of TDP-43 can be transferred from cell-to-cell in a seed-dependent and self-templating manner. Here, we review clinical and experimental studies supporting the prion-like spreading of misfolded TDP-43 and discuss the molecular mechanisms underlying the propagation of these pathological aggregated proteins. The idea that misfolded TDP-43 spreads in a prion-like manner between cells may guide novel therapeutic strategies for TDP-43-associated neurodegenerative diseases.
Anti-oncogene PTPN13 inactivation by hepatitis B virus X protein counteracts IGF2BP1 to promote hepatocellular carcinoma progression
Authors: Yan Yongcong , Huang Pinbo , Mao Kai , He Chuanchao , Xu Qiaodong , Zhang Mengyu , Liu Haohan , Zhou Zhenyu , Zhou Qiming , Zhou Qianlei , Ou Bing , Liu Qinghua , Lin Jianhong , Chen Ruibin , Wang Jie , Zhang Jianlong , Xiao Zhiyu
Published: October 2020

Hepatitis B x protein (HBx) affects cellular protein expression and participates in the tumorigenesis and progression of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). Metabolic reprogramming contributed to the HCC development, but its role in HBV-related HCC remains largely unclear. Tyrosine-protein phosphatase nonreceptor type 13 (PTPN13) is a significant regulator in tumor development, however, its specific role in hepatocarcinogenesis remains to be explored. Here, we found that decreased PTPN13 expression was associated with HBV/HBx. Patients with low PTPN13 expression showed a poor prognosis. Functional assays revealed that PTPN13 inhibited proliferation and tumorigenesis in vitro and in vivo. Further mechanistic studies indicated that HBx inhibited PTPN13 expression by upregulating the expression of DNMT3A and interacting with DNMT3A. Furthermore, we found that DNMT3A bound to the PTPN13 promoter (−343 to −313 bp) in an epigenetically controlled manner associated with elevated DNA methylation and then inhibited PTPN13 transcription. In addition, we identified IGF2BP1 as a novel PTPN13-interacting gene and demonstrated that PTPN13 influences c-Myc expression by directly and competitively binding to IGF2BP1 to decrease the intracellular concentration of functional IGF2BP1. Overexpressing PTPN13 promoted c-Myc mRNA degradation independent of the protein tyrosine phosphatase (PTP) activity of PTPN13. Importantly, we discovered that the PTPN13-IGF2BP1-c-Myc axis was important for cancer cell growth through promoting metabolic reprogramming. We verified the significant negative correlations between PTPN13 expression and c-Myc, PSPH, and SLC7A1 expression in clinical HCC tissue samples. In summary, our findings demonstrate that PTPN13 is a novel regulator of HBV-related hepatocarcinogenesis and may play an important role in HCC. PTPN13 may serve as a prognostic marker and therapeutic target in HBV-related HCC patients.
Survival of patients with deficient mismatch repair metastatic colorectal cancer in the pre-immunotherapy era
Authors: Wensink G. Emerens , Elferink Marloes A. G. , May Anne M. , Mol Linda , Hamers Patricia A. H. , Bakker Sandra D. , Creemers Geert-Jan , de Groot Jan Willem B. , de Klerk Gerty J. , Haberkorn Brigitte C. M. , Haringhuizen Annebeth W. , Hoekstra Ronald , Hunting J. Cornelis B. , Kerver Emile D. , Mathijssen-van Stein Danielle , Polée Marco B. , Pruijt Johannes F. M. , Quarles van Ufford-Mannesse Patricia , Radema Sandra , Rietbroek Ronald C. , Simkens Lieke H. J. , Tanis Bea C. , ten Bokkel Huinink Daan , Tjin-A-Ton Manuel L. R. , Tromp-van Driel Cathrien S. , Troost Monique M. , van de Wouw Agnes J. , van den Berkmortel Franchette W. P. J. , van der Pas Anke J. M. , van der Velden Ankie M. T. , van Dijk Marjan A. , van Dodewaard-de Jong Joyce M. , van Druten Edith B. , van Voorthuizen Theo , Jan Veldhuis Gerrit , Verheul Henk M. W. , Vestjens Hanneke J. H. M. J. , Vincent Jeroen , Kranenburg Onno W. , Punt Cornelis J. A. , Vink Geraldine R. , Roodhart Jeanine M. L. , Koopman Miriam
Published: October 2020

Background

Metastatic colorectal cancer patients with deficient mismatch repair (dMMR mCRC) benefit from immunotherapy. Interpretation of the single-arm immunotherapy trials is complicated by insignificant survival data during systemic non-immunotherapy. We present survival data on a large, comprehensive cohort of dMMR mCRC patients, treated with or without systemic non-immunotherapy.

Methods

Two hundred and eighty-one dMMR mCRC patients (n = 54 from three prospective Phase 3 CAIRO trials;n = 227 from the Netherlands Cancer Registry). Overall survival was analysed from diagnosis of mCRC (OS), from initiation of first-line (OS1) and second-line (OS2) systemic treatment. Cox regression analysis examined prognostic factors. As comparison for OS 2746 MMR proficient mCRC patients were identified.

Results

Of 281 dMMR patients, 62% received first-line and 26% second-line treatment. Median OS was 16.0 months (13.8–19.6) with antitumour therapy and 2.5 months (1.8–3.5) in untreated patients. OS1 was 12.8 months (10.7–15.2) and OS2 6.2 months (5.4–8.9) in treated dMMR patients. Treated dMMR patients had a 7.6-month shorter median OS than pMMR patients.

Conclusion

Available data from immunotherapy trials lack a control arm with standard systemic treatment. Given the poor outcome compared to the immunotherapy results, our data strongly suggest a survival benefit of immunotherapy in dMMR mCRC patients.
Droplet-digital PCR reveals frequent mutations in TERT promoter region in breast fibroadenomas and phyllodes tumours, irrespective of the presence of MED12 mutations
Authors: Otsuji Kazutaka , Sasaki Takeshi , Tanabe Masahiko , Seto Yasuyuki
Published: October 2020

Background

Breast fibroadenoma (FA) and phyllodes tumour (PT) often have variations of gene mediator complex subunit 12 (MED12) and mutations in the telomerase reverse transcriptase promoter region (TERTp). TERTp mutation is usually tested by Sanger sequencing. In this study, we compared Sanger sequencing and droplet-digital PCR (ddPCR) to measure TERTp mutations in FA and PT samples.

Methods

FA and PT samples were collected from 82 patients who underwent surgery at our institution from 2005 to 2016. MED12 mutations for all cases and TERTp mutations for 17 tumours were detected by Sanger sequencing. ddPCR was performed to analyse TERTp mutation in all cases.

Results

A total of 75 samples were eligible for analysis. Sanger sequencing detected MED12 mutations in 19/44 FA (42%) and 21/31 PT (68%). Among 17 Sanger sequencing-tested samples, 2/17 (12%) were TERTp mutation-positive. In ddPCR analyses, a significantly greater percentage of PT (19/31, 61%) was TERTp mutation-positive than was FA (13/44, 30%; P = 0.0046). The mutation positivity of TERTp and MED12 did not correlate, in either FA or PT.

Conclusions

ddPCR was more sensitive for detecting TERTp mutation than Sanger sequencing, being able to elucidate tumorigenesis in FA and PT.
Crystal structure of caspase-11 CARD provides insights into caspase-11 activation
Authors: Liu Muziying , Zhou Kang , Xu Zhihao , Ma Huan , Cao Xiaocong , Yin Xueying , Zeng Weihong , Zahid Ayesha , Fu Sicheng , Ni Kang , Ye Xiaodong , Zhou Ying , Bai Li , Zhou Rongbin , Jin Tengchuan
Published: October 2020

Murine caspase-11 is the centerpiece of the non-canonical inflammasome pathway that can respond to intracellular LPS and induce pyroptosis. Caspase-11 contains two components, an N-terminal caspase recruitment domain (CARD) and a C-terminal catalytic domain. The aggregation of caspase-11 is thought to promote the auto-processing and activation of caspase-11. However, the activation mechanism of caspase-11 remains unclear. In this study, we purified the caspase-11 CARD fused to an MBP tag and found it tetramerizes in solution. Crystallographic analysis reveals an extensive hydrophobic interface formed by the H1–2 helix mediating homotypic CARD interactions. Importantly, mutations of the helix H1–2 hydrophobic residues abolished the tetramerization of MBP-tagged CARD in solution and failed to induce pyroptosis in cells. Our study provides the first evidence of the homotypic interaction mode for an inflammatory caspase by crystal model. This finding demonstrates that the tetramerization of the N-terminal CARD can promote releasing of the catalytic domain auto-inhibition, leading to the caspase-11 activation.
A scoping review of adoption of climate-resilient crops by small-scale producers in low- and middle-income countries
Authors: Acevedo Maricelis , Pixley Kevin , Zinyengere Nkulumo , Meng Sisi , Tufan Hale , Cichy Karen , Bizikova Livia , Isaacs Krista , Ghezzi-Kopel Kate , Porciello Jaron
Published: October 2020

Climate-resilient crops and crop varieties have been recommended as a way for farmers to cope with or adapt to climate change, but despite the apparent benefits, rates of adoption by smallholder farmers are highly variable. Here we present a scoping review, using PRISMA-P (Preferred Reporting Items for Systematic review and Meta-Analysis Protocols), examining the conditions that have led to the adoption of climate-resilient crops over the past 30 years in lower- and middle-income countries. The descriptive analysis performed on 202 papers shows that small-scale producers adopted climate-resilient crops and varieties to cope with abiotic stresses such as drought, heat, flooding and salinity. The most prevalent trait in our dataset was drought tolerance, followed by water-use efficiency. Our analysis found that the most important determinants of adoption of climate-resilient crops were the availability and effectiveness of extension services and outreach, followed by education levels of heads of households, farmers’ access to inputs—especially seeds and fertilizers—and socio-economic status of farming families. About 53% of studies reported that social differences such as sex, age, marital status and ethnicity affected the adoption of varieties or crops as climate change-adaptation strategies. On the basis of the collected evidence, this study presents a series of pathways and interventions that could contribute to higher adoption rates of climate-resilient crops and reduce dis-adoption.
A scoping review of feed interventions and livelihoods of small-scale livestock keepers
Authors: Baltenweck Isabelle , Cherney Debbie , Duncan Alan , Eldermire Erin , Lwoga Edda Tandi , Labarta Ricardo , Rao Elizaphan James Oburu , Staal Steven , Teufel Nils
Published: October 2020

Livestock support the livelihoods of one billion people in Africa, Asia and Latin America, but the productivity of animals remains low, reducing the potential of the sector to support higher incomes and better nutrition. Improved livestock feeding has been identified as the most important step towards higher productivity. This scoping review assessed the evidence for the uptake of improved ruminant livestock feed options, the effect of this uptake on livestock productivity and the degree to which this improves smallholder farmer livelihoods. In total, 22,981 papers were identified, of which 73 papers were included in the final analysis after a rigorous double-blind screening review. Only papers that reported farmers’ decision to use a new feed intervention were selected, thereby excluding feeding trials and participatory feed assessments. Of the 73 papers, only 6 reported combined evidence of adoption, effect on productivity and livelihood changes. A total of 58 papers looked at adoption, 19 at productivity change and 22 at livelihood change. This scoping review highlights the gap in evidence for the adoption of new livestock feeding practices and provides recommendations to support farmers’ uptake of feed interventions.
Whole genome sequencing data of multiple individuals of Pakistani descent
Authors: Khan Shahid Y. , Ali Muhammad , Lee Mei-Chong W. , Ma Zhiwei , Biswas Pooja , Khan Asma A. , Naeem Muhammad Asif , Riazuddin Saima , Riazuddin Sheikh , Ayyagari Radha , Hejtmancik J. Fielding , Riazuddin S. Amer
Published: October 2020

Here we report whole genome sequencing of four individuals (H3, H4, H5, and H6) from a family of Pakistani descent. Whole genome sequencing yielded 1084.92, 894.73, 1068.62, and 1005.77 million mapped reads corresponding to 162.73, 134.21, 160.29, and 150.86 Gb sequence data and 52.49x, 43.29x, 51.70x, and 48.66x average coverage for H3, H4, H5, and H6, respectively. We identified 3,529,659, 3,478,495, 3,407,895, and 3,426,862 variants in the genomes of H3, H4, H5, and H6, respectively, including 1,668,024 variants common in the four genomes. Further, we identified 42,422, 39,824, 28,599, and 35,206 novel variants in the genomes of H3, H4, H5, and H6, respectively. A major fraction of the variants identified in the four genomes reside within the intergenic regions of the genome. Single nucleotide polymorphism (SNP) genotype based comparative analysis with ethnic populations of 1000 Genomes database linked the ancestry of all four genomes with the South Asian populations, which was further supported by mitochondria based haplogroup analysis. In conclusion, we report whole genome sequencing of four individuals of Pakistani descent.
A naturalistic neuroimaging database for understanding the brain using ecological stimuli
Authors: Aliko Sarah , Huang Jiawen , Gheorghiu Florin , Meliss Stefanie , Skipper Jeremy I.
Published: October 2020

Neuroimaging has advanced our understanding of human psychology using reductionist stimuli that often do not resemble information the brain naturally encounters. It has improved our understanding of the network organization of the brain mostly through analyses of ‘resting-state’ data for which the functions of networks cannot be verifiably labelled. We make a ‘Naturalistic Neuroimaging Database’ (NNDb v1.0) publically available to allow for a more complete understanding of the brain under more ecological conditions during which networks can be labelled. Eighty-six participants underwent behavioural testing and watched one of 10 full-length movies while functional magnetic resonance imaging was acquired. Resulting timeseries data are shown to be of high quality, with good signal-to-noise ratio, few outliers and low movement. Data-driven functional analyses provide further evidence of data quality. They also demonstrate accurate timeseries/movie alignment and how movie annotations might be used to label networks. The NNDb can be used to answer questions previously unaddressed with standard neuroimaging approaches, progressing our knowledge of how the brain works in the real world.
Spotlight on the invasion of a carabid beetle on an oceanic island over a 105-year period
Authors: Lebouvier Marc , Lambret Philippe , Garnier Alexia , Convey Peter , Frenot Yves , Vernon Philippe , Renault David
Published: October 2020

The flightless beetle Merizodus soledadinus, native to the Falkland Islands and southern South America, was introduced to the sub-Antarctic Kerguelen Islands in the early Twentieth Century. Using available literature data, in addition to collecting more than 2000 new survey (presence/absence) records of M. soledadinus over the 1991–2018 period, we confirmed the best estimate of the introduction date of M. soledadinus to the archipelago, and tracked subsequent changes in its abundance and geographical distribution. The range expansion of this flightless insect was initially slow, but has accelerated over the past 2 decades, in parallel with increased local abundance. Human activities may have facilitated further local colonization by M. soledadinus, which is now widespread in the eastern part of the archipelago. This predatory insect is a major threat to the native invertebrate fauna, in particular to the endemic wingless flies Anatalanta aptera and Calycopteryx moseleyi which can be locally eliminated by the beetle. Our distribution data also suggest an accelerating role of climate change in the range expansion of M. soledadinus, with populations now thriving in low altitude habitats. Considering that no control measures, let alone eradication, are practicable, it is essential to limit any further local range expansion of this aggressively invasive insect through human assistance. This study confirms the crucial importance of long term biosurveillance for the detection and monitoring of non-native species and the timely implementation of control measures.
Sulcal morphology of ventral temporal cortex is shared between humans and other hominoids
Authors: Miller Jacob A. , Voorhies Willa I. , Li Xiang , Raghuram Ishana , Palomero-Gallagher Nicola , Zilles Karl , Sherwood Chet C. , Hopkins William D. , Weiner Kevin S.
Published: October 2020

Hominoid-specific brain structures are of particular importance in understanding the evolution of human brain structure and function, as they are absent in mammals that are widely studied in the extended neuroscience field. Recent research indicates that the human fusiform gyrus (FG), which is a hominoid-specific structure critical for complex object recognition, contains a tertiary, longitudinal sulcus (mid-fusiform sulcus, MFS) that bisects the FG into lateral and medial parallel gyri. The MFS is a functional and architectonic landmark in the human brain. Here, we tested if the MFS is specific to the human FG or if the MFS is also identifiable in other hominoids. Using magnetic resonance imaging and cortical surface reconstructions in 30 chimpanzees and 30 humans, we show that the MFS is also present in chimpanzees. The MFS is relatively deeper and cortically thinner in chimpanzees compared to humans. Additional histological analyses reveal that the MFS is not only present in humans and chimpanzees, but also in bonobos, gorillas, orangutans, and gibbons. Taken together, these results reveal that the MFS is a sulcal landmark that is shared between humans and other hominoids. These results require a reconsideration of the sulcal patterning in ventral temporal cortex across hominoids, as well as revise the compensation theory of cortical folding.
Boron improves cardiac contractility and fibrotic remodeling following myocardial infarction injury
Authors: Bouchareb Rihab , Katz Michael , Saadallah Najla , Sassi Yassine , Ali Shakir , Lebeche Djamel
Published: October 2020

Myocardial fibrosis is a major determinant of clinical outcomes in heart failure (HF) patients. It is characterized by the emergence of myofibroblasts and early activation of pro-fibrotic signaling pathways before adverse ventricular remodeling and progression of HF. Boron has been reported in recent years to augment the innate immune system and cell proliferation, which play an important role in the repair and regeneration of the injured tissue. Currently, the effect of boron on cardiac contractility and remodeling is unknown. In this study, we investigated, for the first time, the effect of boron supplementation on cardiac function, myocardial fibrosis, apoptosis and regeneration in a rat model myocardial infarction (MI)-induced HF. MI was induced in animals and borax, a sodium salt of boron, was administered for 7 days, p.o., 21 days post-injury at a dose level of 4 mg/kg body weight. Transthoracic echocardiographic analysis showed a significant improvement in systolic and diastolic functions with boron treatment compared to saline control. In addition, boron administration showed a marked reduction in myocardial fibrosis and apoptosis in the injured hearts, highlighting a protective effect of boron in the ischemic heart. Interestingly, we observed a tenfold increase of nuclei in thin myocardial sections stained positive for the cell cycle marker Ki67 in the MI boron-treated rats compared to saline, indicative of increased cardiomyocyte cell cycle activity in MI hearts, highlighting its potential role in regeneration post-injury. We similarly observed increased Ki67 and BrdU staining in cultured fresh neonatal rat ventricular cardiomyocytes. Collectively, the results show that boron positively impacted MI-induced HF and attenuated cardiac fibrosis and apoptosis, two prominent features of HF. Importantly, boron has the potential to induce cardiomyocyte cell cycle entry and potentially cardiac tissue regeneration after injury. Boron might be beneficial as a supplement in MI and may be a good candidate substance for anti-fibrosis approach.
Enhanced energy density of PVDF-based nanocomposites via a core–shell strategy
Authors: Xu JingJing , Fu Chao , Chu Huiying , Wu Xianyou , Tan Zhongyang , Qian Jing , Li Weiyan , Song Zhongqian , Ran Xianghai , Nie Wei
Published: October 2020

In recent years, high energy density polymer capacitors have attracted a lot of scientific interest due to their potential applications in advanced power systems and electronic devices. Here, core–shell structured TiO2@SrTiO3@polydamine nanowires (TiO2@SrTiO3@PDA NWs) were synthesized via a combination of surface conversion reaction and in-situ polymerization method, and then incorporated into the poly(vinylidene fluoride) (PVDF) matrix. Our results showed that a small amount of TiO2@SrTiO3@PDA NWs can simultaneously enhance the breakdown strength and electric displacement of nanocomposite (NC) films, resulting in improved energy storage capability. The 5 wt% TiO2@SrTiO3@PDA NWs/PVDF NC demonstrates 1.72 times higher maximum discharge energy density compared to pristine PVDF (10.34 J/cm3 at 198 MV/m vs. 6.01 J/cm3 at 170 MV/m). In addition, the NC with 5 wt% TiO2@SrTiO3@PDA NWs also demonstrates an excellent charge–discharge efficiency (69% at 198 MV/m). Enhanced energy storage performance is due to hierarchical interfacial polarization among their multiple interfaces, the large aspect ratio as well as surface modification of the TiO2@SrTiO3 NWs. The results of this study provide guidelines and a foundation for the preparation of the polymer NCs with an outstanding discharge energy density.
Motor cortical circuits contribute to crossed facilitation of trunk muscles induced by rhythmic arm movement
Authors: Chiou Shin-Yi , Morris Laura , Gou Weidong , Alexander Emma , Gay Eliot
Published: October 2020

Training of one limb improves performance of the contralateral, untrained limb, a phenomenon known as cross transfer. It has been used for rehabilitation interventions, i.e. mirror therapy, in people with neurologic disorders. However, it remains unknown whether training of the upper limb can induce the cross-transfer effect to the trunk muscles. Using transcranial magnetic stimulation over the primary motor cortex (M1) we examined motor evoked potentials (MEPs) in the contralateral erector spinae (ES) muscle before and after 30 min of unilateral arm cycling in healthy volunteers. ES MEPs were increased after the arm cycling. To understand the origin of this facilitatory effect, we examined short-interval intracrotical inhibition (SICI) and cervicomedullary MEPs (CMEPs) in neural populations controlling in the ES muscle. Notably, SICI reduced after the arm cycling, while CMEPs remained the same. Using bilateral transcranial direct current stimulation (tDCS) in conjunction with 20 min of the arm cycling, the amplitude of ES MEPs increased to a similar extent as with 30 min of the arm cycling alone. These findings demonstrate that a single session of unilateral arm cycling induces short-term plasticity in corticospinal projections to the trunk muscle in healthy humans. The changes are likely driven by cortical mechanisms.
Modulatory effects of BPC 157 on vasomotor tone and the activation of Src-Caveolin-1-endothelial nitric oxide synthase pathway
Authors: Hsieh Ming-Jer , Lee Cheng-Hung , Chueh Ho-Yen , Chang Gwo-Jyh , Huang Hsiu-Yun , Lin Yuling , Pang Jong-Hwei S.
Published: October 2020

BPC 157-activated endothelial nitric oxide synthase (eNOS) is associated with tissue repair and angiogenesis as reported in previous studies. However, how BPC 157 regulates the vasomotor tone and intracellular Src-Caveolin-1 (Cav-1)-eNOS signaling is not yet clear. The present study demonstrated a concentration-dependent vasodilation effect of BPC 157 in isolated rat aorta. Attenuation of this vasodilation effect in the absence of endothelium suggested an endothelium-dependent vasodilation effect of BPC 157. Although slightly increased vasorelaxation in aorta without endothelium was noticed at high concentration of BPC 157, there was no direct relaxation effect on three-dimensional model made of vascular smooth muscle cells. The vasodilation effect of BPC 157 was nitric oxide mediated because the addition of L-NAME or hemoglobin inhibited the vasodilation of aorta. Nitric oxide generation was induced by BPC 157 as detected by intracellular DFA-FM DA labeling which was capable of promoting the migration of vascular endothelial cells. BPC 157 enhanced the phosphorylation of Src, Cav-1 and eNOS which was abolished by pretreatment with Src inhibitor, confirming the upstream role of Src in this signal pathway. Activation of eNOS required the released binding with Cav-1 in advance. Co-immunoprecipitation analysis revealed that BPC 157 could reduce the binding between Cav-1 and eNOS. Together, the present study demonstrates that BPC 157 can modulate the vasomotor tone of an isolated aorta in a concentration- and nitric oxide-dependent manner. BPC 157 can induce nitric oxide generation likely through the activation of Src-Cav-1-eNOS pathway.