bluuebunny/crossref_metadata_2025 huggingface dataset:
824 MOLECULAR UNDERPINNINGS OF NEUROENDOCRINE DIFFERENTIATION IN ESOPHAGEAL ADENOCARCINOMA AND ITS PROGNOSTIC SIGNIFICANCE
Authors: Wilson G , Elimova E , Yeung J , Darling G , N Kalimuthu S
Published: September 2021

The presence of neuroendocrine (NE) differentiation has been previously reported in both morphological subtypes, (intestinal and diffuse), of esophageal adenocarcinoma, (EAC). This is more commonly seen in the post-treatment setting and is thought to confer a more aggressive phenotype. However, the molecular underpinning and therapeutic implications of NE differentiation within EAC is poorly understood. Herein, the goal is to understand the molecular mechanisms, evolution and the prognostic significance of NE development in EAC tumours.

Methods

We interrogated a previously published transcriptome dataset with matched H&E slides, TCGA EAC (N = 86). Moreover, we have begun reviewing H&E slides from EAC patients from UHN (N = 50). We created a NE gene expression signature (N = 25 genes) from the literature as an initial proof of concept. We quantified the presence of a NET-like/organoid morphology in the matched H&E slides and correlated it with the average z-score of the NE gene signature calculated from the matched transcriptome data.

Results

NE differentiation was present in 27/86 cases with a mean of 21.01% +/− 20.9 within the tumour area. We compared the expression of our NE gene signature with the proportion of NE morphology and observed a moderate correlation between morphology with the gene expression (R^2 = 0.546, P < 0.001 ordinary least squares regression), providing validation that the organoid/NET-like morphological pattern correlates with NE differentiation. Furthermore, we have validated the presence of NE morphology in a subset of the UHN samples using electron microscopy and immunohistochemistry (chromogranin and synaptophysin).

Conclusion

This is a first of a kind study to profile a specific morphology with a transcriptional signature within EAC across a large cohort of patient samples. Correlation of NE-features with clinical outcome together with treatment resistant implications is currently underway.
851 TRANSHIATAL ESOPHAGECTOMY: A SELECTIVE ROLE IN THE CURATIVE APPROACH TO ESOPHAGEAL CANCER
Authors: Butt Waqas , Donlon Noel E , Bolger Jarlath C , Donohoe Claire L , Ravi Narayanasamy , Reynolds John V
Published: September 2021

Surgery remains central to the curative management of esophageal cancer. At this Center, based on evidence from the literature, transthoracic en bloc surgery (TTE) is standard, however transhiatal esophagectomy (THE) is considered for predicted early stage junctional (AEG) tumors, multifocal in situ cancer, or where age or respiratory co-morbidity suggests a high risk with TTE. This audit reports this experience over 19 years.

Methods

Data was acquired from our prospectively maintained database. Patients who underwent esophagectomy with curative intent and gastric tube reconstruction for mid/distal esophageal or esophagogastric junction cancer (cT1-4aN0-3 M0) from 2000 to 2018 were included. THE was compared with TTE for operative complications (ECCG-defined), and proxy markers of oncologic quality.

Results

933 patients were included, 166 (18%) THE and 767 (82%) TTE. The median (range) age was 62(22–83) vs 67(36–86) in TTE and THE, with 43(6%) and 40(24%) over 75 respectively (p < 0.01). There were significantly (p < 0.01) more early tumors in the THE (58%) vs the TTE group(11%). 23% were > ASA 3 in THE vs 12% TTE (p < 0.01). Postoperative pulmonary complications (PPCs) were 11% and 18.3% in THE and TTE cohorts, respectively(p 0.03). In-hospital mortality was 1.2%vs3.4% in THE vs TTE (p = 0.21). Five-year survival was 67% and 40% in THE vs TTE, respectively.

Conclusion

These data are consistent with the safe and effective use of THE in selected cases. Notably, favourable major pulmonary morbidity and mortality rates for a higher risk cohort. We suggest that this approach may still be relevant in defined scenarios in an increasingly minimally invasive era.
855 OPTIMIZATION OF SURGICAL DELAY AFTER INDUCTION CHEMORADIATION FOR ESOPHAGEAL CANCER: 10 YEARS RETROSPECTIVE MULTI-CENTER STUDY
Authors: Legault-Dupuis Alexis , Bouchard Philippe , Nicodème Frederic , Gagne Jean-Pierre , Simard Serge , Lacasse Yves , Hache Pier-Luc , Couture Christian , Laliberte Anne-Sophie
Published: September 2021

The treatment of esophageal cancer is in constant evolution. Most of the esophageal cancer receive induction chemoradiation therapy. Surgical delay has been studied but the optimal timing has not been clarified. Through the years, surgical delay has been modified by surgeons in our institutions, going from an average of 6 weeks delay to an average of 10 weeks delay. It is time to ask if this change has a real positive impact on our patient.

Methods

In this retrospective multi-center study, we combined data from two center in Quebec city that performs oncologic esophagectomy. The surgical delay went from 6 to 10 weeks around 2014. All surgeons changed their practice at that moment. We retrospectively analysed 5 years before and after the change of practice and created two cohorts of patients. Our primary outcome compared complete pathologic response rate. Our secondary outcomes were surgical complications, anastomotic leak, disease free survival and overall survival.

Results

Thirty-eight patients had surgery under 8 weeks (mean: 6 weeks) after their induction chemoradiation compared to 64 patients that had surgery after 8 weeks (mean: 10 weeks). There was no statistical significant difference between groups for the complete pathologic response (32% vs 25%, p = 0,16). Important complications were similar, with a rate of 24% vs 28% (p = 0,69). Anastomotic leaks were less frequent in the less than 8 weeks group, but no statistical significance was obtained (13% vs 27%, p = 0,14).No difference in the disease-free survival rate and overall survival rate was noted (DFS 40% vs 55% (p = 0,32), OS 38% vs 38% (p = 0,29)).

Conclusion

The treatment of esophageal cancer is in constant evolution, induction therapy and surgical technics involve over time. Surgical delay has no impact on complete pathologic response, complication and overall survival. There is no advantage to wait longer before surgery.
93 A CASE OF G-CSF(GRANULOCYTE-COLONY STIMULATING FACTOR) PRODUCING ESOPHAGEAL CANCER WITH ENTEROBLASTIC DIFFERENTIATION
Authors: Kitamura Yu , Oshikiri Taro , Takiguchi Gosuke , Urakawa Naoki , Hasegawa Hiroshi , Yamamoto Masashi , Kanaji Shingo , Matsuda Yoshiko , Yamashita Kimihiro , Matsuda Takeru , Nakamura Tetsu , Suzuki Satoshi , Kakeji Yoshihiro
Published: September 2021

Granulocyte-colony stimulating factor (G-CSF) producing tumor is one type of growth factor producing tumor that induces leukocytosis. On the other hand, adenocarcinoma with enteroblastic differentiation disease is known as α-fetprotein (AFP), glypican3, and Sal-like protein 4 (SALL4) producing tumor.

We report a first case of G-CSF producing esophageal cancer with enteroblastic differentiation which has never been reported in the world.

Methods

[Case presentation]: A fifty-six year-old man was admitted to our hospital to treat esophageal carcinoma.

His body temperature was elevated. Blood biochemistry tests showed leukocytosis (WBC 14000/μl).

Gastroscopy revealed a 10-cm diameter, superficial elevated lesion in the lower thoracic esophagus.

Biopsy findings indicated a diagnosis of adenocarcinoma. No distant metastasis, but right subclavian and para esophageal lymph nodes swelling were identified via computed tomography.

Thus, we planned neo adjuvant chemotherapy (NAC) (5-FU 800 mg/m2 plus Cisplatin 80 mg/m2) before surgical resection. The patient’s hyperthermia and leukocytosis improved by not antibiotics but NAC.

Therefore, we suspected G-CSF producing tumor.

Results

The serum level of G-CSF was markedly elevated at 133 pg/ml (normal range, <39 pg/ml).

Additionally, PET/CT showed abnormally high uptake of (18) F-FDG not only by the tumor itself, but also diffusely throughout the bone marrow.

The patient underwent minimally invasive esophagectomy in the prone position with two-field lymph node dissection.

Immunohistochemical studies showed G-CSF producing adenocarcinoma with enteroblastic differentiation (AFP negative, glypican3 and SALL4 positive). Pathological stage was pT2N0M0, stageII.

After resection, improvement of hyperthermia, leukocytosis, and serum level of G-CSF can be seen. Findings of (18) F-FDG throughout the bone marrow were also disappeared.

Conclusion

We experienced an extremely rare case of G-CSF producing, esophageal adenocarcinoma with enteroblastic differentiation.
Managing the Gender Wage Gap—How Female Managers Influence the Gender Wage Gap among Workers
Authors: Zimmermann Florian
Published: September 2021

Previous research shows that female managers narrow the gender wage gap (GWG) among workers but does not disentangle two general underlying mechanisms. First, female managers might use their organizational power to change organizational practices and make organizations more gender-equal. Second, female workers might benefit from interacting with a female manager, e.g. through homophily and mentoring. To disentangle these two mechanisms, I distinguish between female managers at the first management level, which is responsible mainly for organizational practices, and at the second management level, which mainly interacts with workers. Additionally, I consider practices enhancing gender equality, such as work-life balance practices. Using German linked employer–employee panel data and a firm fixed-effects regression, I find that female first-level managers slightly narrow the GWG. This influence is not affected by the consideration of organizational practices. Hence, female first-level managers do not affect workers’ by changing organizational practices. In contrast, female second-level managers considerably narrow the GWG among workers. In summary, female managers substantially reduce the GWG among workers, and this effect works via the manager–worker interaction mechanism. Hence, increasing the share of female second-level managers might close the GWG.
Five-year outcomes after state-of-the-art percutaneous coronary revascularization in patients with de novo three-vessel disease: final results of the SYNTAX II study
Authors: Banning Adrian P , Serruys Patrick , De Maria Giovanni Luigi , Ryan Nicola , Walsh Simon , Gonzalo Nieves , Jan van Geuns Robert , Onuma Yoshinobu , Sabate Manel , Davies Justin , Lesiak Maciej , Moreno Raul , Cruz-Gonzalez Ignacio , Hoole Stephen P , Piek Jan J , Appleby Clare , Fath-Ordoubadi Farzin , Zaman Azfar , Van Mieghem Nicolas M , Uren Neal , Zueco Javier , Buszman Pawel , Iniguez Andres , Goicolea Javier , Hildick-Smith David , Ochala Andrzej , Dudek Dariusz , de Vries Ton , Taggart David , Farooq Vasim , Spitzer Ernest , Tijssen Jan , Escaned Javier
Published: September 2021

Aims

The SYNTAX II study evaluated the impact of advances in percutaneous coronary intervention (PCI), integrated into a single revascularization strategy, on outcomes of patients with de novo three-vessel disease. The study employed decision-making utilizing the SYNTAX score II, use of coronary physiology, thin-strut biodegradable polymer drug-eluting stents, intravascular ultrasound, enhanced treatments of chronic total occlusions, and optimized medical therapy. Patients treated with this approach were compared with predefined patients from the SYNTAX I trial.

Methods and results

SYNTAX II was a multicentre, single-arm, open-label study of patients requiring revascularization who demonstrated clinical equipoise for treatment with either coronary artery bypass grafting (CABG) or PCI, predicted by the SYNTAX score II. The primary endpoint was major adverse cardiac and cerebrovascular events (MACCE), which included any revascularization. The comparators were a matched PCI cohort trial and a matched CABG cohort, both from the SYNTAX I trial. At 5 years, MACCE rate in SYNTAX II was significantly lower than in the SYNTAX I PCI cohort (21.5% vs. 36.4%, P < 0.001). This reflected lower rates of revascularization (13.8% vs. 23.8%, P < 0.001), and myocardial infarction (MI) (2.7% vs. 10.4%, P < 0.001), consisting of both procedural MI (0.2% vs. 3.8%, P < 0.001) and spontaneous MI (2.3% vs. 6.9%, P = 0.004). All-cause mortality was lower in SYNTAX II (8.1% vs. 13.8%, P = 0.013) reflecting a lower rate of cardiac death (2.8% vs. 8.4%, P < 0.001). Major adverse cardiac and cerebrovascular events’ outcomes at 5 years among patients in SYNTAX II and predefined patients in the SYNTAX I CABG cohort were similar (21.5% vs. 24.6%, P = 0.35).

Conclusions

Use of the SYNTAX II PCI strategy in patients with de novo three-vessel disease led to improved and durable clinical results when compared to predefined patients treated with PCI in the original SYNTAX I trial. A predefined exploratory analysis found no significant difference in MACCE between SYNTAX II PCI and matched SYNTAX I CABG patients at 5-year follow-up.
Implementation of two policies to extend maternity leave and further restrict marketing of breast milk substitutes in Vietnam: a qualitative study
Authors: Payán Denise Diaz , Zahid Neha , Glenn Jeffrey , Tran Ha TT , Huong Tran Thi Thu , Moucheraud Corrina
Published: September 2021

Policy research can reveal gaps and opportunities to enhance policy impact and implementation. In this study, we use a theoretically informed qualitative approach to investigate the implementation of two policies to promote breastfeeding in Vietnam. We conducted semi-structured interviews with national and local policy stakeholders (n = 26) in 2017. Interviews were audio-recorded, transcribed verbatim and then translated to English by certified translators. Transcript data were analysed using an integrated conceptual framework of policy implementation. Respondents identified several positive outcomes resulting from implementation of an extended maternity leave policy (Labour Code No. 10/2012/QH13) and further restrictions on marketing of breast milk substitutes (Decree No. 100/2014/ND-CP). Decree No. 100, in particular, was said to have reduced advertising of breast milk substitutes in mass media outlets and healthcare settings. Key implementation actors were national-level bureaucratic actors, local organizations and international partners. Findings reveal the importance of policy precedence and a broader set of policies to promote the rights of women and children to support implementation. Other facilitators were involvement from national-level implementing agencies and healthcare personnel and strength of government relationships and coordination with non-governmental and international organizations. Implementation challenges included insufficient funding, limited training to report violations, a cumbersome reporting process and pervasive misinformation about breast milk and breast milk substitutes. Limited reach for women employed in the informal labour sector and in rural communities was said to be a compatibility issue for the extended maternity leave policy in addition to the lack of impact on non-parental guardians and caretakers. Recommendations to improve policy implementation include designating a role for international organizations in supporting implementation, expanding maternity protections for all working women, building local-level policy knowledge to support enforcement, simplifying Decree No. 100 violation reporting processes and continuing to invest in interventions to facilitate a supportive policy environment in Vietnam.
‘What have the Ottomans ever done for us?’ Why history matters for politics in the Arab Middle East
Authors: Neep Daniel
Published: September 2021

Scholars of Middle East politics have been reluctant to explore how the long nineteenth century has shaped the region's political development. The reason for this neglect, I argue, is a common understanding of Ottoman decline and failed modernization, which suggests that the story of modern politics in the Middle East commences with colonial partition after the First World War. But what if political scientists are getting the story wrong? In this article, I argue that our background assumptions about the political development of the Middle East reflect outdated understandings that historians themselves have long left behind. Drawing on this revisionist Ottoman historiography, I show that key dynamics in Middle East politics today—such as state-building and sectarian identities—originate not in the era ushered in by the Sykes–Picot Accord, but in the transformations of the long nineteenth century. By overlooking the evolution of late Ottoman politics and their historical legacies, political scientists risk misdiagnosing key dynamics in the region's political development. ‘Bringing the Ottomans back in’ highlights to policy-makers the importance of the extra-institutional dimensions of statebuilding in the Middle East, and opens up new vistas for research in comparative–historical political science.
Explicit incorporation of spatial variability in a biomass dynamics assessment model
Authors: McDonald Raphaël R , Keith David M , Sameoto Jessica A , Hutchings Jeffrey A , Flemming Joanna M
Published: September 2021

The sustainable management of fisheries has largely relied on stock assessment models that assume stocks are homogeneous throughout their domain. However, ignoring complex underlying spatial patterns can lead to increased risk of failures in management. Utilizing geostatistical approaches in conjunction with a traditional fishery biomass dynamics model, we develop a spatially-explicit modelling framework that treats the underlying population dynamics as spatial processes. Simulation experiments demonstrate that this approach reliably estimates variance parameters and accurately captures true patterns of population change. We further demonstrate the utility of our modelling framework in a real setting using data from the Canadian Maritimes Inshore Scallop Fishery. The model captures time-varying spatial patterns in both population characteristics and fishing pressure without explicit knowledge of the underlying mechanisms and retains the ability to scale up to the whole spatial domain with less associated uncertainty than for temporal models. These results lead to improved scientific advice for management, future-proofing of the assessment to shifts in stock productivity and fishing effort, and provide information that can be used to develop more effective management approaches.
Unipotent Quantum Coordinate Ring and Prefundamental Representations for TypesAn(1) andDn(1)
Authors: Jang Il-Seung , Kwon Jae-Hoon , Park Euiyong
Published: September 2021

We give a new realization of the prefundamental representations $L^\pm _{r,a}$ introduced by Hernandez and Jimbo, when the quantum loop algebra $U_q(\mathfrak {g})$ is of types $A_n^{(1)}$ and $D_n^{(1)}$ and the $r$-th fundamental weight $\varpi _r$ for types $A_n$ and $D_n$ is minuscule. We define an action of the Borel subalgebra $U_q(\mathfrak {b})$ of $U_q(\mathfrak {g})$ on the unipotent quantum coordinate ring associated to the translation by $-\varpi _r$ and show that it is isomorphic to $L^\pm _{r,a}$. We then give a combinatorial realization of $L^+_{r,a}$ in terms of the Lusztig data of the dual PBW vectors.
Talking with an IoT-CA: Effects of the Use of Internet of Things Conversational Agents on Face-to-Face Conversations
Authors: Li Ziyang , Rau Pei-Luen Patrick
Published: September 2021

Internet of things conversational agents (IoT-CAs) are making human–computer interactions ubiquitous. In this study, we experimentally examined the effects of IoT-CA use on face-to-face conversations between close partners. A total of 136 participants (68 close relationship dyads) participated in the experiment. We prepared an IoT chat environment and provided chat topics for each dyad. The dyads were randomly assigned into one of two IoT-CA use pattern groups (joint use: two persons using an IoT-CA together; individual use: one person using an IoT-CA alone) and three interaction conditions (no IoT-CA use, conversation content-relevant IoT-CA use, conversation content-irrelevant IoT-CA use). The results showed that compared with no IoT-CA use, IoT-CA use did not have negative effects on conversation experiences but produced feelings of greater closeness to the IoT-CA in the partners. Furthermore, joint IoT-CA use in the content-relevant condition (IoT-CA made comments relevant to interpersonal interactions) helped increase interpersonal self-disclosure.
Development and validation of a prognostic model for non-lung cancer death in elderly patients treated with stereotactic body radiotherapy for non-small cell lung cancer
Authors: Hanazawa Hideki , Matsuo Yukinori , Takeda Atsuya , Tsurugai Yuichiro , Iizuka Yusuke , Kishi Noriko , Takehana Keiichi , Mizowaki Takashi
Published: September 2021

This study sought to develop and validate a prognostic model for non-lung cancer death (NLCD) in elderly patients with non-small cell lung cancer (NSCLC) treated with stereotactic body radiotherapy (SBRT). Patients aged ≥65 diagnosed with NSCLC (Tis-4N0M0), tumor diameter ≤5 cm and SBRT between 1998 and 2015 were retrospectively registered from two independent institutions. One institution was used for model development (arm D, 353 patients) and the other for validation (arm V, 401 patients). To identify risk factors for NLCD, multiple regression analysis on age, sex, performance status (PS), body mass index (BMI), Charlson comorbidity index (CCI), tumor diameter, histology and T-stage was performed on arm D. A score calculated using the regression coefficient was assigned to each factor and three risk groups were defined based on total score. Scores of 1.0 (BMI ≤18.4), 1.5 (age ≥ 5), 1.5 (PS ≥2), 2.5 (CCI 1 or 2) and 3 (CCI ≥3) were assigned, and risk groups were designated as low (total ≤ 3), intermediate (3.5 or 4) and high (≥4.5). The cumulative incidences of NLCD at 5 years in the low, intermediate and high-risk groups were 6.8, 23 and 40% in arm D, and 23, 19 and 44% in arm V, respectively. The AUC index at 5 years was 0.705 (arm D) and 0.632 (arm V). The proposed scoring system showed usefulness in predicting a high risk of NLCD in elderly patients treated with SBRT for NSCLC.
Who is
Authors: Kahl Oliver
Published: September 2021

This short article proposes an explanation of the opaque term which makes an isolated appearance in an Arabic medico-philosophical encyclopedia from the third/ninth century; a possible derivation of the contextually related graphogram is briefly discussed on that occasion as well.
Knock down of NON-YELLOW COLOURING 1-like gene or chlorophyllin application enhanced chlorophyll accumulation with antioxidant roles in suppressing heat-induced leaf senescence in perennial ryegrass
Authors: Yu Guohui , Xie Zheni , Chen Wei , Xu Bin , Huang Bingru
Published: September 2021

Loss of chlorophyll and oxidative damage co-occur during heat-induced leaf senescence. This study aimed to determine the functions of a chlorophyll catabolic gene, NON-YELLOW COLOURING 1 (NYC1)-like (NOL), in regulating heat-induced leaf senescence and to characterize antioxidant roles of a chlorophyll derivative, sodium copper chlorophyllin (SCC), in suppressing heat-induced leaf senescence. In two separate experiments, one by comparing NOL RNAi transgenic and wild-type plants, and the other by analysing the effects of SCC treatment, perennial ryegrass (Lolium perenne) was exposed to heat stress (38/35 °C, day/night) or optimal temperature (25/20 °C). Results showed that both knock down of LpNOL and application of SCC suppressed heat-induced leaf senescence, as manifested by increased chlorophyll content, reduced electrolyte leakage, down-regulation of chlorophyll-catabolic genes and senescence-related genes, as well as enhanced antioxidant capacity in the peroxidase pathway for H2O2 scavenging. Ex vivo SCC incubation protected membranes from H2O2 damage in mesophyll protoplasts of perennial ryegrass. The suppression of leaf senescence by knocking down

NOL or chlorophyllin application was associated with enhanced chlorophyll accumulation playing antioxidant roles in protecting leaves from heat-induced oxidative damage.
The Galactic neutron star population – I. An extragalactic view of the Milky Way and the implications for fast radio bursts
Authors: Chrimes A A , Levan A J , Groot P J , Lyman J D , Nelemans G
Published: September 2021

A key tool astronomers have to investigate the nature of extragalactic transients is their position on their host galaxies. Galactocentric offsets, enclosed fluxes, and the fraction of light statistic are widely used at different wavelengths to help infer the nature of transient progenitors. Motivated by the proposed link between magnetars and fast radio bursts (FRBs), we create a face-on image of the Milky Way using best estimates of its size, structure, and colour. We place Galactic magnetars, pulsars, low-mass, and high-mass X-ray binaries on this image, using the available distance information. Galactocentric offsets, enclosed fluxes, and fraction of light distributions for these systems are compared to extragalactic transient samples. We find that FRBs follow the distributions for Galactic neutron stars closest, with 24 (75 per cent) of the Anderson–Darling tests we perform having a p-value greater than 0.05. This suggests that FRBs are located on their hosts in a manner consistent with Galactic neutron stars on the Milky Way’s light, although we cannot determine which specific neutron star population is the best match. The Galactic distributions are consistent with other extragalactic transients much less often across the range of comparisons made, with type Ia SNe in second place, at only 33 per cent of tests exceeding 0.05. Overall, our results provide further support for FRB models invoking isolated young neutron stars, or binaries containing a neutron star.
Signature and escape of highly fractionated plasma in an active region
Authors: Brooks David H , Yardley Stephanie L
Published: September 2021

Accurate forecasting of space weather requires knowledge of the source regions where solar energetic particles (SEP) and eruptive events originate. Recent work has linked several major SEP events in 2014, January, to specific features in the host active region (AR 11944). In particular, plasma composition measurements in and around the footpoints of hot, coronal loops in the core of the active region were able to explain the values later measured in situ by the Wind spacecraft. Due to important differences in elemental composition between SEPs and the solar wind, the magnitude of the Si/S elemental abundance ratio emerged as a key diagnostic of SEP seed population and solar wind source locations. We seek to understand if the results are typical of other active regions, even if they are not solar wind sources or SEP productive. In this paper, we use a novel composition analysis technique, together with an evolutionary magnetic field model, in a new approach to investigate a typical solar active region (AR 11150), and identify the locations of highly fractionated (high Si/S abundance ratio) plasma. Material confined near the footpoints of coronal loops, as in AR 11944, that in this case have expanded to the AR periphery, show the signature, and can be released from magnetic field opened by reconnection at the AR boundary. Since the fundamental characteristics of closed field loops being opened at the AR boundary is typical of active regions, this process is likely to be general.
Identifying potential exomoon signals with convolutional neural networks
Authors: Teachey Alex , Kipping David
Published: September 2021

Targeted observations of possible exomoon host systems will remain difficult to obtain and time-consuming to analyse in the foreseeable future. As such, time-domain surveys such as Kepler, K2, and TESS will continue to play a critical role as the first step in identifying candidate exomoon systems, which may then be followed up with premier ground- or space-based telescopes. In this work, we train an ensemble of convolutional neural networks (CNNs) to identify candidate exomoon signals in single-transit events observed by Kepler. Our training set consists of ∼27 000 examples of synthetic, planet-only, and planet + moon single transits, injected into Kepler light curves. We achieve up to 88 per cent classification accuracy with individual CNN architectures and 97 per cent precision in identifying the moons in the validation set when the CNN ensemble is in total agreement. We then apply the CNN ensemble to light curves from 1880 Kepler Objects of Interest with periods >10 d (∼57 000 individual transits), and further test the accuracy of the CNN classifier by injecting planet transits into each light curve, thus quantifying the extent to which residual stellar activity may result in false positive classifications. We find a small fraction of these transits contain moon-like signals, though we caution against strong inferences of the exomoon occurrence rate from this result. We conclude by discussing some ongoing challenges to utilizing neural networks for the exomoon search.
Radiation hydrodynamical simulations of the birth of intermediate-mass black holes in the first galaxies
Authors: Latif Muhammad A , Khochfar Sadegh , Schleicher Dominik , Whalen Daniel J
Published: September 2021

The leading contenders for the seeds of z > 6 quasars are direct-collapse black holes (DCBHs) forming in atomically cooled haloes at z ∼ 20. However, the Lyman–Werner (LW) UV background required to form DCBHs of 105 M⊙ are extreme, about 104 J21, and may have been rare in the early universe. Here we investigate the formation of intermediate-mass black holes (IMBHs) under moderate LW backgrounds of 100 and 500 J21, which were much more common at early times. These backgrounds allow haloes to grow to a few 106–107 M⊙ and virial temperatures of nearly 104 K before collapsing, but do not completely sterilize them of H2. Gas collapse then proceeds via Lyα and rapid H2 cooling at rates that are 10–50 times those in normal Pop III star-forming haloes, but less than those in purely atomically cooled haloes. Pop III stars accreting at such rates become blue and hot, and we find that their ionizing UV radiation limits their final masses to 1800–2800 M⊙ at which they later collapse to IMBHs. Moderate LW backgrounds thus produced IMBHs in far greater numbers than DCBHs in the early universe.
AutoProf – I. An automated non-parametric light profile pipeline for modern galaxy surveys
Authors: Stone Connor J , Arora Nikhil , Courteau Stéphane , Cuillandre Jean-Charles
Published: September 2021

We present an automated non-parametric light profile extraction pipeline called autoprof. All steps for extracting surface brightness (SB) profiles are included in autoprof, allowing streamlined analyses of galaxy images. autoprof improves upon previous non-parametric ellipse fitting implementations with fit-stabilization procedures adapted from machine learning techniques. Additional advanced analysis methods are included in the flexible pipeline for the extraction of alternative brightness profiles (along radial or axial slices), smooth axisymmetric models, and the implementation of decision trees for arbitrarily complex pipelines. Detailed comparisons with widely used photometry algorithms (photutils, xvista, and galfit) are also presented. These comparisons rely on a large collection of late-type galaxy images from the PROBES catalogue. The direct comparison of SB profiles shows that autoprof can reliably extract fainter isophotes than other methods on the same images, typically by >2 mag arcsec−2. Contrasting non-parametric elliptical isophote fitting with simple parametric models also shows that two-component fits (e.g. Sérsic plus exponential) are insufficient to describe late-type galaxies with high fidelity. It is established that elliptical isophote fitting, and in particular autoprof, is ideally suited for a broad range of automated isophotal analysis tasks. autoprof is freely available to the community at: https://github.com/ConnorStoneAstro/AutoProf.
HENMT1 is involved in the maintenance of normal female fertility in the mouse
Authors: Hutt Karla J , Lim Shu Ly , Zhang Qing-Hua , Gonzalez Maria , O’Connor Anne E , Merriner D Jo , Liew Seng H , Al-Zubaidi Usama , Yuen Wai Shan , Adhikari Deepak , Robker Rebecca L , Mann Jeffrey R , Carroll John , O’Bryan Moira K
Published: September 2021

PIWI-interacting small RNAs (piRNAs) maintain genome stability in animal germ cells, with a predominant role in silencing transposable elements. Mutations in the piRNA pathway in the mouse uniformly lead to failed spermatogenesis and male sterility. By contrast, mutant females are fertile. In keeping with this paradigm, we previously reported male sterility and female fertility associated with loss of the enzyme HENMT1, which is responsible for stabilising piRNAs through the catalysation of 3′-terminal 2′-O-methylation. However, the Henmt1 mutant females were poor breeders, suggesting they could be subfertile. Therefore, we investigated oogenesis and female fertility in these mice in greater detail. Here, we show that mutant females indeed have a 3- to 4-fold reduction in follicle number and reduced litter sizes. In addition, meiosis-II mutant oocytes display various spindle abnormalities and have a dramatically altered transcriptome which includes a down-regulation of transcripts required for microtubule function. This down-regulation could explain the spindle defects observed with consequent reductions in litter size. We suggest these various effects on oogenesis could be exacerbated by asynapsis, an apparently universal feature of piRNA mutants of both sexes. Our findings reveal that loss of the piRNA pathway in females has significant functional consequences.
A vast pool of lineage-specific microproteins encoded by long non-coding RNAs in plants
Authors: Fesenko Igor , Shabalina Svetlana A , Mamaeva Anna , Knyazev Andrey , Glushkevich Anna , Lyapina Irina , Ziganshin Rustam , Kovalchuk Sergey , Kharlampieva Daria , Lazarev Vassili , Taliansky Michael , Koonin Eugene V
Published: September 2021

Pervasive transcription of eukaryotic genomes results in expression of long non-coding RNAs (lncRNAs) most of which are poorly conserved in evolution and appear to be non-functional. However, some lncRNAs have been shown to perform specific functions, in particular, transcription regulation. Thousands of small open reading frames (smORFs, <100 codons) located on lncRNAs potentially might be translated into peptides or microproteins. We report a comprehensive analysis of the conservation and evolutionary trajectories of lncRNAs-smORFs from the moss Physcomitrium patens across transcriptomes of 479 plant species. Although thousands of smORFs are subject to substantial purifying selection, the majority of the smORFs appear to be evolutionary young and could represent a major pool for functional innovation. Using nanopore RNA sequencing, we show that, on average, the transcriptional level of conserved smORFs is higher than that of non-conserved smORFs. Proteomic analysis confirmed translation of 82 novel species-specific smORFs. Numerous conserved smORFs containing low complexity regions (LCRs) or transmembrane domains were identified, the biological functions of a selected LCR-smORF were demonstrated experimentally. Thus, microproteins encoded by smORFs are a major, functionally diverse component of the plant proteome.
Receptor tyrosine kinases as druggable targets in glioblastoma: Do signaling pathways matter?
Authors: Qin Anna , Musket Anna , Musich Phillip R , Schweitzer John B , Xie Qian
Published: September 2021

Glioblastoma (GBM) is the most malignant primary brain tumor without effective therapies. Since bevacizumab was FDA approved for targeting vascular endothelial growth factor receptor 2 (VEGFR2) in adult patients with recurrent GBM, targeted therapy against receptor tyrosine kinases (RTKs) has become a new avenue for GBM therapeutics. In addition to VEGFR, the epidermal growth factor receptor (EGFR), platelet-derived growth factor receptor (PDGFR), hepatocyte growth factor receptor (HGFR/MET), and fibroblast growth factor receptor (FGFR) are major RTK targets. However, results from clinical Phase II/III trials indicate that most RTK-targeting therapeutics including tyrosine kinase inhibitors (TKIs) and neutralizing antibodies lack clinical efficacy, either alone or in combination. The major challenge is to uncover the genetic RTK alterations driving GBM initiation and progression, as well as to elucidate the mechanisms toward therapeutic resistance. In this review, we will discuss the genetic alterations in these 5 commonly targeted RTKs, the clinical trial outcomes of the associated RTK-targeting therapeutics, and the potential mechanisms toward the resistance. We anticipate that future design of new clinical trials with combination strategies, based on the genetic alterations within an individual patient’s tumor and mechanisms contributing to therapeutic resistance after treatment, will achieve durable remissions and improve outcomes in GBM patients.
La protection des enfants et des adolescents contre les risques du vapotage
Authors: Chadi Nicholas , Vyver Ellie , Bélanger Richard E
Published: September 2021

Le vapotage chez les jeunes comporte des risques importants pour la santé et la sécurité des enfants et des adolescents canadiens. Le présent document de principes fournit de l’information générale sur le vapotage et les produits et dispositifs qui y sont liés, traite des méfaits à court et à long terme associés à leur utilisation et propose des stratégies de prévention et d’abandon pour les jeunes vapoteurs ou ceux qui sont à risque de commencer à vapoter. Le vapotage chez les jeunes est associé à un risque accru d’usage de tabac et de substances psychoactives, de troubles de santé mentale, de pneumopathie, de cardiopathie et de blessures accidentelles. Le vapotage ne doit pas servir d’outil d’abandon du tabac chez les jeunes, en raison de son manque d’efficacité et des données probantes sur les méfaits qu’il occasionne. De nombreuses stratégies préventives et thérapeutiques utilisées pour l’abandon du tabac, y compris les stratégies comportementales et pharmacologiques, peuvent être adaptées pour aider les jeunes à arrêter de vapoter. Des recommandations sont formulées pour les intervenants communautaires et les décideurs.
Diketopiperazine Modulates Arabidopsis thaliana Root System Architecture by Promoting Interactions of Auxin Receptor TIR1 and IAA7/17 Proteins
Authors: Yin Lujun , Chen Xiaodong , Chen Qi , Wei Dongqing , Hu Xiang-Yang , Jia Ai-Qun
Published: September 2021

Plants can detect the quorum sensing (QS) signaling molecules of microorganisms, such as amino acids, fat derivatives and diketopiperazines (DKPs), thus allowing the exchange information to promote plant growth and development. Here, we evaluated the effects of 12 synthesized DKPs on Arabidopsis thaliana roots and studied their underlying mechanisms of action. Results showed that, as QS signal molecules, the DKPs promoted lateral root development and root hair formation in A.thaliana to differing degrees. The DKPs enhanced the polar transport of the plant hormone auxin from the shoot to root and triggered the auxin-responsive protein IAA7/17 to decrease the auxin response factor, leading to the accumulation of auxin at the root tip and accelerated root growth. In addition, the DKPs induced the development of lateral roots and root hair in the A. thaliana root system architecture via interference with auxin receptor transporter inhibitor response protein 1 (TIR1). A series of TIR1 sites that potentially interact with DKPs were also predicted using molecular docking analysis. Mutations of these sites inhibited the phosphorylation of TIR1 after DKP treatment, thereby inhibiting lateral root formation, especially TIR1-1 site. This study identified several DKP signal molecules in the QS system that can promote the expression of auxin response factors ARF7/19 via interactions of TIR1 and IAA7/17 proteins, thus promoting plant growth and development.
Molecular mechanisms of endomembrane trafficking in plants
Authors: Aniento Fernando , Sánchez de Medina Hernández Víctor , Dagdas Yasin , Rojas-Pierce Marcela , Russinova Eugenia
Published: September 2021

Endomembrane trafficking is essential for all eukaryotic cells. The best-characterized membrane trafficking organelles include the endoplasmic reticulum (ER), Golgi apparatus, early and recycling endosomes, multivesicular body, or late endosome, lysosome/vacuole, and plasma membrane. Although historically plants have given rise to cell biology, our understanding of membrane trafficking has mainly been shaped by the much more studied mammalian and yeast models. Whereas organelles and major protein families that regulate endomembrane trafficking are largely conserved across all eukaryotes, exciting variations are emerging from advances in plant cell biology research. In this review, we summarize the current state of knowledge on plant endomembrane trafficking, with a focus on four distinct trafficking pathways: ER-to-Golgi transport, endocytosis, trans-Golgi network-to-vacuole transport, and autophagy. We acknowledge the conservation and commonalities in the trafficking machinery across species, with emphasis on diversity and plant-specific features. Understanding the function of organelles and the trafficking machinery currently nonexistent in well-known model organisms will provide great opportunities to acquire new insights into the fundamental cellular process of membrane trafficking.
A dual role for glutathione transferase U7 in plant growth and protection from methyl viologen-induced oxidative stress
Authors: Ugalde José Manuel , Lamig Liliana , Herrera-Vásquez Ariel , Fuchs Philippe , Homagk Maria , Kopriva Stanislav , Müller-Schüssele Stefanie J , Holuigue Loreto , Meyer Andreas J
Published: September 2021

Plant glutathione S-transferases (GSTs) are glutathione-dependent enzymes with versatile functions, mainly related to detoxification of electrophilic xenobiotics and peroxides. The Arabidopsis (Arabidopsis thaliana) genome codes for 53 GSTs, divided into seven subclasses; however, understanding of their precise functions is limited. A recent study showed that class II TGA transcription factors TGA2, TGA5, and TGA6 are essential for tolerance of UV-B-induced oxidative stress and that this tolerance is associated with an antioxidative function of cytosolic tau-GSTs (GSTUs). Specifically, TGA2 controls the expression of several GSTUs under UV-B light, and constitutive expression of GSTU7 in the tga256 triple mutant is sufficient to revert the UV-B-susceptible phenotype of tga256. To further study the function of GSTU7, we characterized its role in mitigation of oxidative damage caused by the herbicide methyl viologen (MV). Under non-stress conditions, gstu7 null mutants were smaller than wild-type (WT) plants and delayed in the onset of the MV-induced antioxidative response, which led to accumulation of hydrogen peroxide and diminished seedling survival. Complementation of gstu7 by constitutive expression of GSTU7 rescued these phenotypes. Furthermore, live monitoring of the glutathione redox potential in intact cells with the fluorescent probe Grx1-roGFP2 revealed that GSTU7 overexpression completely abolished the MV-induced oxidation of the cytosolic glutathione buffer compared with WT plants. GSTU7 acted as a glutathione peroxidase able to complement the lack of peroxidase-type GSTs in yeast. Together, these findings show that GSTU7 is crucial in the antioxidative response by limiting oxidative damage and thus contributes to oxidative stress resistance in the cell.
Evaluation of factors affecting patients’ refusal of HCV treatment in a cohort of Egyptian patients
Authors: Hashem Mohamed B , Badary Hedy A , Mahfouz Noha A , Adel Shaden , Alboraie Mohamed , AbdAllah Mohamed , AlAkel Wafaa , Saeed Ramy , Ammar Islam , Abdel-Razek Wael , Hassany Mohamed , Esmat Gamal
Published: September 2021

Background

Treatment refusal, defined as active refusal of a patient to receive treatment despite physician recommendations, has not been extensively evaluated before in hepatitis C virus in the era of direct acting antivirals.

Objective

To investigate the reasons for refusal to receive hepatitis C virus treatment in Egypt.

Methods

an observational study conducted between July 2018 and November 2019 in Egypt. Enrollment was done to all patients who refused to get hepatitis C virus treatment during the national screening and treatment campaign. Reasons for their refusal were identified using a questionnaire as an instrument for data collection.

Results

Out of the 220 280 Egyptian hepatitis C virus patients who did not show up to start treatment and were contacted to get therapy, only 84 patients (0.038%) refused to receive treatment. The main reason for their refusal was having concerns about treatment (82.14%) and their main concern was the fear of adverse events (85.5%). Other causes of refusal were non-satisfactory experience at treatment centers (13.09%) and patients preferred to receive complementary and alternative medicines (4.7%). Most patients (65.4%) trusted the efficacy of directly acting antivirals for hepatitis C. None of the study participants was found to suffer from any psychiatric morbidity and the average score of the GHQ-12 was 10.7155.

Conclusion

Proper health education and awareness regarding hepatitis C virus treatment safety and efficacy is needed to increase treatment acceptance rates.
Organic nitrogen enhances nitrogen nutrition and early growth ofPinus sylvestrisseedlings
Authors: Lim Hyungwoo , Jämtgård Sandra , Oren Ram , Gruffman Linda , Kunz Sabine , Näsholm Torgny
Published: September 2021

Boreal trees are capable of taking up organic nitrogen (N) as effectively as inorganic N. Depending on the abundance of soil N forms, plants may adjust physiological and morphological traits to optimize N uptake. However, the link between these traits and N uptake in response to soil N sources is poorly understood. We examined Pinus sylvestris L. seedlings’ biomass growth and allocation, transpiration and N uptake in response to additions of organic N (the amino acid arginine) or inorganic N (ammonium nitrate). We also monitored in situ soil N fluxes in the pots following an addition of N, using a microdialysis system. Supplying organic N resulted in a stable soil N flux, whereas the inorganic N resulted in a sharp increase of nitrate flux followed by a rapid decline, demonstrating a fluctuating N supply and a risk for loss of nitrate from the growth medium. Seedlings supplied with organic N achieved a greater biomass with a higher N content, thus reaching a higher N recovery compared with those supplied inorganic N. In spite of a higher N concentration in organic N seedlings, root-to-shoot ratio and transpiration per unit leaf area were similar to those of inorganic N seedlings. We conclude that enhanced seedlings’ nutrition and growth under the organic N source may be attributed to a stable supply of N, owing to a strong retention rate in the soil medium.
Distal Radius Fractures: Setting Yourself Up for Success in the Active Geriatric Patient
Authors: Medda Suman , Aneja Arun , Carroll Eben A.
Published: September 2021

Distal radius fractures are common in the geriatric population; however, treatment of these fractures remains controversial. Patients undergoing operative fixation may experience a quicker recovery with increased grip strength, which is beneficial in the active geriatric patient. Treatment options include fragment-specific fixation, volar locked plating, and dorsal bridge plating. External fixation alone leads to poor outcomes and is indicated in patients with soft tissue compromise or as a supplemental aid. Implant selection should be tailored to fracture parameters. With a thoughtful surgical algorithm and rehabilitation protocol, good outcomes can be achieved with a high rate of patient satisfaction.