bluuebunny/crossref_metadata_2025 huggingface dataset:
Indigo Carmine Dye–Assisted Lymphatic-Sparing Microsurgical Subinguinal Varicocelectomy Among Children and Adolescents
Authors: Ando Satoshi , Nakamura Shigeru , Hyuga Taiju , Tanabe Kazuya , Nakai Hideo , Fujimura Tetsuya
Published: April 2022

The purpose of this study is to clarify the safety and efficacy of indigo carmine dye–assisted lymphatic-sparing microsurgical subinguinal varicocelectomy for children and adolescents in our institution. Medical records of boys aged ≤ 15 years who underwent varicocelectomy between November 2008 and December 2019 at our institution were retrospectively reviewed. Microsurgical subinguinal varicocelectomy was performed using indigo carmine injection under the tunica vaginalis to preserve lymphatics. A total of 29 patients underwent varicocelectomy, among whom six underwent retroperitoneal high ligation (modified Palomo technique), nine underwent laparoscopic varicocelectomy, and 14 underwent microsurgical subinguinal varicocelectomy. The median operative time for retroperitoneal high ligation, laparoscopic varicocelectomy, and microsurgical subinguinal varicocelectomy was 71 (IQR: 59–82.5) min, 131 (95–151) min, and 125.5 (112–134.25) min, respectively. Among the patients who underwent laparoscopic varicocelectomy, one and two experienced hydrocele and varicocele recurrence as postoperative complications, respectively. None of the patients who underwent microsurgical subinguinal varicocelectomy developed hydrocele and varicocele recurrence during 15.5-month median follow-up period (IQR: 11.25–25.75 month). Indigo carmine dye–assisted lymphatic-sparing microsurgical subinguinal varicocelectomy can be a safe and efficient treatment modality among children and adolescents.
Prognostic value of post-percutaneous coronary intervention diastolic pressure ratio
Authors: Masdjedi K. , van Zandvoort L. J. C. , Neleman T. , Kardys I. , Ligthart J. , Den Dekker W. K. , Diletti R. , Zijlstra F. , Van Mieghem N. M. , Daemen J.
Published: April 2022

Aim

To evaluate the distribution of a generic diastolic pressure ratio (dPR) after angiographically successful percutaneous coronary intervention (PCI) and to assess its association with the 2‑year incidence of target vessel failure (TVF), defined as a composite of cardiac mortality, target vessel revascularisation, target vessel myocardial infarction and stent thrombosis.

Methods

The dPR SEARCH study is a post hoc analysis of the prospective single-centre FFR-SEARCH registry, in which physiological assessment was performed after angiographically successful PCI in a total of 1000 patients, using a dedicated microcatheter. dPR was calculated offline with recently validated software in a subset of 735 patients.

Results

Mean post-PCI dPR was 0.95 ± 0.06. Post-PCI dPR was ≤ 0.89 in 15.2% of the patients. The cumulative incidence of TVF at 2‑year follow-up was 9.4% in patients with a final post-PCI dPR ≤ 0.89 as compared to 6.1% in patients with a post-PCI dPR > 0.89 (adjusted hazard ratio [HR] for dPR ≤ 0.89: 1.53; 95% CI 0.74–3.13; p = 0.249). dPR ≤ 0.89 was associated with significantly higher cardiac mortality at 2 years; adjusted HR 2.40; 95% CI 1.01–5.68; p = 0.047.

Conclusions

In a real-world setting, despite optimal angiographic PCI results, 15.2% of the patients had a final post-PCI dPR of ≤ 0.89, which was associated with a higher incidence of TVF and a significantly higher cardiac mortality rate.
Enhancing students’ beliefs regarding programming self-efficacy and intrinsic value of an online distributed Programming Environment
Authors: Daradoumis Thanasis , Marquès Puig Joan Manuel , Arguedas Marta , Calvet Liñan Laura
Published: April 2022

Several studies have explored the factors that influence self-efficacy as well as its contribution to academic development in online learning environments in recent years. However, little research has investigated the effect of a web-based learning environment on enhancing students’ beliefs about self-efficacy for learning. This is especially noticeable in the field of online distributed programming. We need to design online learning environments for programming education that foster both students’ self-efficacy for programming learning and the added value that students perceive of the tool as a successful learning environment. To that end, we conducted a quantitative analysis to collect and analyze data of students using an online Distributed Systems Laboratory (DSLab) in an authentic, long-term online educational experience. The results indicate that (1) our distributed programming learning tool provides an environment that increases students’ belief of programming self-efficacy; (2) the students’ experience with the tool strengthens their belief in the intrinsic value of the tool; however (3) the relationship between students’ belief in the tool intrinsic value and their self-efficacy is inconclusive. This study provides relevant implications for online distributed (or general) programming course teachers who seek to increase students’ engagement, learning and performance in this field.
A method for the experimental characterisation of novel drag-reducing materials for very low Earth orbits using the Satellite for Orbital Aerodynamics Research (SOAR) mission
Authors: Crisp Nicholas H. , Roberts Peter C. E. , Hanessian Virginia , Sulliotti-Linner Valeria , Herdrich Georg H. , García-Almiñana Daniel , Kataria Dhiren , Seminari Simon
Published: April 2022

The Satellite for Orbital Aerodynamics Research (SOAR) is a 3U CubeSat mission that aims to investigate the gas–surface interactions (GSIs) of different materials in the very low Earth orbit environment (VLEO), i.e. below 450 km. Improving the understanding of these interactions is critical for the development of satellites that can operate sustainably at these lower orbital altitudes, with particular application to future Earth observation and communications missions. SOAR has been designed to perform the characterisation of the aerodynamic coefficients of four different materials at different angles of incidence with respect to the flow and at different altitudes in the VLEO altitude range. Two conventional and erosion-resistant materials (borosilicate glass and sputter-coated gold) have first been selected to support the validation of the ground-based Rarefied Orbital Aerodynamics Research (ROAR) facility. Two further, novel materials have been selected for their potential to reduce the drag experienced in orbit whilst also remaining resistant to the detrimental effects of atomic oxygen erosion in VLEO. In this paper, the uncertainty associated with the experimental method for determining the aerodynamic coefficients of satellite with different configurations of the test materials from on-orbit data is estimated for different assumed gas–surface interaction properties. The presented results indicate that for reducing surface accommodation coefficients the experimental uncertainty on the drag coefficient determination generally increases, a result of increased aerodynamic attitude perturbations. This effect is also exacerbated by the high atmospheric density at low orbital altitude (i.e. 200 km), resulting in high experimental uncertainty. Co-rotated steerable fin configurations are shown to provide generally lower experimental uncertainty than counter-rotated configurations, with the lowest uncertainties expected in the mid-VLEO altitudes ($$\sim$$
∼
300 km). For drag coefficient experiments, configurations with two fins oriented at 90$$^{\circ }$$

∘

were found to allow the best differentiation between surfaces with different GSI performance. In comparison, the determination of the lift coefficient is found to be improve as the altitude is reduced from 400 to 200 km. These experiments were also found to show the best expected performance in determining the GSI properties of different materials. SOAR was deployed into an orbit of 421 km $$\times$$
×
 415 km with 51.6$$^{\circ }$$

∘

inclination on 14 June 2021. This orbit will naturally decay allowing access to different altitudes over the lifetime of the mission. The results presented in this paper will be used to plan the experimental schedule for this mission and to maximise the scientific output.
Inclusive, colour-blind, and deficit: Understanding teachers' contradictory views of Aboriginal students’ participation in education
Authors: Weuffen Sara , Maxwell Jacinta , Lowe Kevin
Published: April 2022

This paper contributes evidence-based scholarship to how teachers understand the value of Aboriginal student-focussed programmes and how discourses of Indigeneity appear to influence those views. Interviews withn = 22 teachers acrossn = 3 secondary school sites in New South Wales highlighted teachers’ understanding of Aboriginal programmes as primarily contributing to students’ behavioural and academic improvement. The interviewed teachers spoke positively about Aboriginal students’ current academic achievements and prospects for their bright futures as graduates, albeit from within deficit and colour-blind discourses. Utilising Moodie’s Decolonising Race Theory framework, teachers’ juxtaposing beliefs resonate with existing decolonising education research which indicates a performativity of cultural inclusion through adherence to settler-colonial practices, while at the same time, an intellectual desire to move away from the legacy of Australia’s contentious colonial past.
Under pressure and overlooked: the impact of COVID-19 on teachers in NSW public schools
Authors: Fray Leanne , Jaremus Felicia , Gore Jennifer , Miller Andrew , Harris Jess
Published: April 2022

The COVID-19 pandemic has put unprecedented pressure on teachers around the world, raising significant concerns about their workload and wellbeing. Our comparison of 2019 (pre-pandemic) and 2020 (first year of the pandemic) survey data (n = 362) from teachers in New South Wales, Australia, demonstrates that their morale and efficacy declined significantly during COVID-19, even with the relatively short period of school closure (8 weeks) during 2020. Interviews with teachers and school leaders (n = 18) reinforced these findings and highlighted the depth to which teachers felt dispensable and unappreciated, despite working incredibly hard for their students. The pressure to adapt to online teaching and learning, in trying circumstances, also challenged their confidence in their teaching. We argue that practical and emotional support for teachers both during periods of remote learning and upon students’ return to the classroom is essential to support teacher’s wellbeing and a robust teaching workforce into the future.
Effect of the Heat Input on Wire-Arc Additive Manufacturing of Invar 36 Alloy: Microstructure and Mechanical Properties
Authors: Veiga Fernando , Suárez Alfredo , Artaza Teresa , Aldalur Eider
Published: April 2022

Invar, also known as FeNi36, is a material of great interest due to its unique properties, which makes it an excellent alternative for sectors such as tooling in aeronautics and aerospace. Its manufacture by means of wire arc additive manufacturing (WAAM) technology could extend its use. This paper aims to evaluate the comparison of two of the most widespread WAAM technologies: plasma arc welding (PAW) and gas metal arc welding (GMAW). This comparison is based on the analysis of wall geometry, metallography, and mechanical properties of the material produced by both technologies. The results show a slight increase in toughness and elongation before fracture and worse tensile strength data in the case of PAW, with average values of 485 MPa for ultimate tensile strength (UTS), 31% for elongation and 475 MPa, 40% in GMAW and PAW, respectively. All results gathered from the analysis show the possibility of successful manufacturing of Invar by means of WAAM technologies. The novelties presented in this paper allow us to establish relationships between the thermal input of the process itself and the mechanical and metallographic properties of the material produced.
Implicit optimal variational collaborative filtering
Authors: Walker Joojo , Zhou Fan , Baagyere Edward Y. , Ahene Emmanuel , Zhang Fengli
Published: April 2022

Recently, variational autoencoder (VAE), a model that supports Bayesian inference and variational posterior distribution approximation, has been used to address the prevailing challenge of inefficient modelling of non-linear user-item interactions in collaborative filtering (CF). However, the choices of prior distributions in these VAE-based CF models are inadequate to determine the underlying distributions, leading to skewed maximum likelihood estimation of model parameters. In this paper, we present an Implicit Optimal Variational autoencoder model for collaborative filtering (IOVA-CF) to alleviate this challenge. Specifically, IOVA-CF utilizes a novel implicit optimal prior, which aids in generating excellent latent representations. This implicit optimal prior (IoP) is an aggregated posterior prior (AP), that is, the posterior’s expectation of the data distribution. However, unlike previous AP, IoP utilizes the density ratio technique to compute the Kullback-Leibler (KL) divergence without explicitly capturing the aggregated posterior. Besides, we can calculate the KL divergence between the aggregated posterior and the inference network in a closed-form using the density ratio technique, making IoP an optimal prior for maximizing the objective function. Additionally, unlike earlier VAE-based recommendation models, IOVA-CF significantly alleviates the over-regularization issue. Furthermore, IOVA-CF can adequately capture the latent space’s uncertainty. Finally, empirical evaluations with several competitive baseline models on four (4) real-world datasets reveal the superior performance of IOVA-CF.
Surgical-site infection after hip fracture surgery: preoperative full-body disinfection compared to local disinfection of the surgical site—a population-based observational cohort study
Authors: Probert Noelle , Andersson Åsa G. , Magnuson Anders , Kjellberg Elin , Wretenberg Per
Published: April 2022

Purpose

Swedish national guidelines recommend full-body disinfection (FBD) with 4% chlorhexidine before hip fracture surgery to prevent surgical-site infection (SSI) despite little evidence. Our objective was to compare preoperative FBD with local disinfection (LD) of the surgical site regarding SSI incidence.

Methods

All patients with hip fracture, operated at a hospital in Sweden, January 1, 2018 to December 31, 2019 were included. Patients in 2018 (n = 237) were prepared with FBD and patients in 2019 (n = 259) with LD. Primary outcome was SSI and secondary outcome was SSI and/or death. We adjusted for potential confounders with logistic regression. The adjusted analysis was performed in two models to enable assessment of variables that lacked either outcome; in the first model, these variables were not adjusted, and the second model was restricted to a sub-population not affected by respective variables.

Results

There were 16 (6.8%) cases of SSI in 2018 and 8 (3.1%) cases in 2019. FBD (2018) compared to LD (2019) presented an adjusted OR of 1.9 (95%CI 0.8–4.9, P = 0.16) respectively 2.0 (95%CI 0.8–5.1, P = 0.14) in the two models of the logistic regression. In addition, 40 (16.9%) patients in 2018 and 29 (11.2%) patients in 2019 had the combined outcome of SSI and/or death, adjusted OR 1.6 (95% CI 0.9–2.8, P = 0.08) respectively 1.7 (95% CI 0.9–2.9, P = 0.06).

Conclusion

We found a non-significant increased risk of SSI 2018 compared to 2019 after adjustment. Randomized control trials are needed. Nonetheless, results suggest that LD is not inferior to FBD regarding SSI prevention, meaning patients could potentially be spared substantial pain.
The Quest for Knowledge in International Relations
Authors: Lebow Richard Ned
Published: April 2022

What do we mean by theory in international relations? What kinds of knowledge do theories seek? How do they stipulate it is found? How should we evaluate any resulting knowledge claims? What do answers to these questions tell us about the theory project in IR, and in the social sciences more generally? Lebow explores these questions in a critical evaluation of the positivist and interpretivist epistemologies. He identifies tensions and problems specific to each epistemology, and some shared by both, and suggests possible responses. By exploring the relationship between the foundations of theories and the empirical assumptions they encode, Lebow's analysis enables readers to examine in greater depth the different approaches to theory and their related research strategies. This book will be of interest to students and scholars of international relations theory and philosophy of social science.
Vaccines as Technology
Authors: Santos Rutschman Ana
Published: April 2022

The COVID-19 pandemic served as a powerful wake-up call, highlighting our collective need for the effective development and equitable distribution of new vaccines, in addition to widespread administration of existing ones. The current models of production and allocation of vaccines against emerging pathogens, which rely on predominantly market-driven mechanisms, are largely at odds with public health needs. This book is the first to explore the entire arc of vaccine development and distribution, from the decisions about allocation of vaccine R&D money to allocation and administration of vaccines resulting from the R&D process. It explains key concepts and problems in vaccine regulation, intellectual property, technology transfer, and international relations, making complex material accessible to a non-specialist audience. Analyzing the impact of COVID-19, the book also covers several other vaccine races, as well as future directions in vaccine development and allocation.
Designing and Evaluating Language Corpora
Authors: Egbert Jesse , Biber Douglas , Gray Bethany
Published: April 2022

Corpora are ubiquitous in linguistic research, yet to date, there has been no consensus on how to conceptualize corpus representativeness and collect corpus samples. This pioneering book bridges this gap by introducing a conceptual and methodological framework for corpus design and representativeness. Written by experts in the field, it shows how corpora can be designed and built in a way that is both optimally suited to specific research agendas, and adequately representative of the types of language use in question. It considers questions such as 'what types of texts should be included in the corpus?', and 'how many texts are required?' – highlighting that the degree of representativeness rests on the dual pillars of domain considerations and distribution considerations. The authors introduce, explain, and illustrate all aspects of this corpus representativeness framework in a step-by-step fashion, using examples and activities to help readers develop practical skills in corpus design and evaluation.
A geometric view of closure phases in interferometry
Authors: Thyagarajan Nithyanandan , Carilli Chris L.
Published: April 2022

Closure phase is the phase of a closed-loop product of spatial coherences formed by a

${\ge}3$

-element interferometer array. Its invariance to phase corruption attributable to individual array elements acquired during the propagation and the measurement processes, subsequent calibration, and errors therein, makes it a valuable tool in interferometry applications that otherwise require high-accuracy phase calibration. However, its understanding has remained mainly mathematical and limited to the aperture plane (Fourier dual of the image plane). Here, we present a geometrical, image domain view of closure phase, which until now has been lacking. Using the principal triangle in a 3-element interference image formed by a triad of interferometer elements, we show that the properties of closure phase, particularly its invariance to multiplicative element-based corruption factors (even of a large magnitude) and to translation, are intricately related to the conserved properties of the triangle, namely, its shape, orientation, and size, which is referred herein as the ‘shape-orientation-size (SOS) conservation principle’. In the absence of a need for element-based amplitude calibration of the interferometer array (as is typical in optical interferometry), the principal triangle in any 3-element interference image formed from phase-uncalibrated spatial coherences is still a true and uncorrupted representation of the source object’s morphology, except for a possible shift. Based on this knowledge of the triangle SOS conservation principle, we present two geometric methods to measure the closure phase directly from a simple 3-element interference image (without requiring an aperture-plane view): (i) the closure phase is directly measurable from any one of the triangle’s heights, and (ii) the squared closure phase is proportional to the product of the areas enclosed by the triad of array elements and the principal triangle in the aperture and image planes, respectively. We validate the geometric understanding of closure phase in the image plane using observations with the Karl G. Jansky Very Large Array, and the Event Horizon Telescope. These results verify the SOS conservation principle across a wide range of radio interferometric conditions. This geometric insight can be potentially valuable to other interferometric applications, such as optical interferometry. We also generalise these geometric relationships to an N-element interferometer.
Transformation from the Ottoman State to the Modern Republic of Turkey: The Renewal Party and Karakol
Authors: Altinkas Evren
Published: April 2022

After the end of WWI, the leaders of Committee of Union and Progress (CUP) established a political party, Renewal Party, and an underground organization, Karakol, in order to organize a resistance against the Allies and their presence in Ottoman territories. These institutions played an important role in the formation of national resistance in Anatolia before Mustafa Kemal's arrival in the region. The establishment of local resistance forces by former CUP members in Anatolia under the name of Renewal Party and the formation of a network in Istanbul to facilitate the smuggling of weapons, ammunition, former military officers, and Unionists to Anatolia were crucial for the formation of a national resistance movement to be organized under the leadership of Mustafa Kemal after May 1919. This article focuses on these two institutions and their role in Turkish National Struggle.
Education or Indoctrination? The Violent Origins of Public School Systems in an Era of State-Building
Authors: PAGLAYAN AGUSTINA S.
Published: April 2022

Why do modern states regulate and provide mass education? This article proposes a theory of education as a state-building tool that is deployed when mass violence threatens the state’s viability. Experiencing mass violence can heighten national elites’ anxiety about the masses’ moral character and raise concerns about the efficacy of repression or concessions alone to maintain social order. In this context, a mass education system designed to teach obedience can become an attractive policy tool to prevent future rebellion and promote long-term order. Consistent with the theory, I detect a cross-national pattern of primary education expansion following civil wars in Europe and Latin America. In a complementary study of the 1859 Chilean civil war, I show that the central government responded by expanding primary schooling in rebel provinces not as a concession but to teach obedience and respect for authority. The theory helps explain why nondemocracies often expanded mass education.
Weed management in a direct-seeded rice-ratoon rice cropping system
Authors: Satapathy Bhabani Sankar , Chatterjee Dibyendu , Saha Sanjoy , Duary Buddhadeb , Singh Teekam
Published: April 2022

A field study was conducted to evaluate the effect of weed management practices in the main crop on growth, yield and economics of rice- ratoon rice cropping system in two consecutive years i.e., 2014–15 and 2015–16. The result showed thatCyperus difformiswas the most dominant weed in the main rice crop, whereasLudwigia adscendeswas the dominant weed in ratoon rice. In weed-free plots, the main crop recorded the highest productivity of 47.52 kg/ha/day, whereas the ratoon crop registered productivity of 37.70 kg/ha/day which was the 79.3% of the main crop productivity. In the weedy plot, crop-weed competition caused 28.8 and 37.5% reduction in energy use efficiency and energy productivity of the rice-ratoon rice cropping system respectively. Yield reduction of 37.3 and 43.6% in the main crop and ratoon crop respectively recorded due to weed infestation in weedy check. All the weed control practices registered an increase in system productivity, nutrient uptake and energy use efficiency. Among the herbicidal treatments, application of bensulfuron-methyl + pretilachlor (60 + 600 g/ha) at 10 DAS to the main crop registered a higher net return of USD$ 639.2 and 260.1 of main crop and ratoon crop, respectively. Hence it can be recommended for weed management in rice-ratoon rice cropping system.
Time-discrete SIR model for COVID-19 in Fiji
Authors: Singh Rishal Amar , Lal Rajnesh , Kotti Ramanuja Rao
Published: April 2022

Using the data provided by Fiji's ministry of health and medical services, we apply an implicit time-discrete SIR (susceptible people–infectious people–removed people) model that tracks the transmission and recovering rate at time, t to predict the trend of the coronavirus disease 2019 (COVID-19) pandemic in Fiji. The model implied time-varying transmission and recovery rates were calculated from 4 May 2021 to 9 October 2021. The estimator functions for these rates were determined, and a short-term (30 days) forecast was done. The model was validated with observed values of the active and recovered cases from 11 October 2021 to 9 December 2021. Statistical results reveal a good fit of profiles between model simulated and the reported COVID-19 data. The gradual decrease of the time-varying basic reproduction number with values below one towards the end of the study period suggest the government's success in controlling the epidemic. The mean reproduction number for the second wave of COVID-19 in Fiji was estimated as 2.7818. The results from this study can be used by researchers, the Fijian government, and the relevant health policy makers in making informed decisions should a third COVID-19 wave occur.
The Duty of Care of Fossil-Fuel Producers for Climate Change Mitigation
Authors: Mayer Benoit
Published: April 2022

On 26 May 2021, the District Court of The Hague (The Netherlands) passed an innovative judgment in Milieudefensie v. Royal Dutch Shell. The Court interpreted Shell's duty of care towards the inhabitants of the Netherlands as requiring it to mitigate climate change by reducing the carbon dioxide emissions resulting from its global operations by at least 45% by 2030, compared with 2019. This case comment salutes the identification of a corporate duty of care for climate change mitigation but expresses scepticism regarding the Court's interpretation of this duty. The Court's reading of global climate mitigation objectives and climate science, which form the basis of its determination of Shell's requisite level of mitigation action, is plagued with inconsistencies. It is argued here that, in order to determine the standard of care applicable to Shell, the Court should have relied not only on a ‘descending’ reasoning as to what ought to be done, but also on an ‘ascending’ reasoning accounting for industry practices.
Scientists Fight to Keep Lidar on the Space Station
Authors: Sidik Saima
Published: April 2022

Remote sensing experts may lose a key tool in the fight against climate change.
Caspase-cleaved tau is senescence-associated and induces a toxic gain of function by putting a brake on axonal transport
Authors: Conze Christian , Rierola Marina , Trushina Nataliya I. , Peters Michael , Janning Dennis , Holzer Max , Heinisch Jürgen J. , Arendt Thomas , Bakota Lidia , Brandt Roland
Published: April 2022

The microtubule-associated protein tau plays a central role in tauopathies such as Alzheimer’s disease (AD). The exact molecular mechanisms underlying tau toxicity are unclear, but aging is irrefutably the biggest risk factor. This raises the question of how cellular senescence affects the function of tau as a microtubule regulator. Here we report that the proportion of tau that is proteolytically cleaved at the caspase-3 site (TauC3) doubles in the hippocampus of senescent mice. TauC3 is also elevated in AD patients. Through quantitative live-cell imaging, we show that TauC3 has a drastically reduced dynamics of its microtubule interaction. Single-molecule tracking of tau confirmed that TauC3 has a longer residence time on axonal microtubules. The reduced dynamics of the TauC3-microtubule interaction correlated with a decreased transport of mitochondria, a reduced processivity of APP-vesicle transport and an induction of region-specific dendritic atrophy in CA1 neurons of the hippocampus. The microtubule-targeting drug Epothilone D normalized the interaction of TauC3 with microtubules and modulated the transport of APP-vesicles dependent on the presence of overexpressed human tau. The results indicate a novel toxic gain of function, in which a post-translational modification of tau changes the dynamics of the tau-microtubule interaction and thus leads to axonal transport defects and neuronal degeneration. The data also introduce microtubule-targeting drugs as pharmacological modifiers of the tau-microtubule interaction with the potential to restore the physiological interaction of pathologically altered tau with microtubules.
TMEM189 negatively regulates the stability of ULK1 protein and cell autophagy
Authors: Yu Jiahong , Qu Liujing , Xia Yan , Zhang Xuan , Feng Jinqiu , Duan Mengyuan , guo Pengli , Lou Yaxin , Lv Ping , Lu Wenping , Chen Yingyu
Published: April 2022

ULK1 is crucial for initiating autophagosome formation and its activity is tightly regulated by post-translational modifications and protein-protein interactions. In the present study, we demonstrate that TMEM189 (Transmembrane protein 189), also known as plasmanylethanolamine desaturase 1 (PEDS1), negatively regulates the proteostasis of ULK1 and autophagy activity. In TMEM189-overexpressed cells, the formation of autophagesome is impaired, whileTMEM189knockdown increases cell autophagy. Further investigation reveals that TMEM189 interacts with and increases the instability of ULK1, as well as decreases its kinase activities. The TMEM189 N-terminal domain is required for the interaction with ULK1. Additionally, TMEM189 overexpression can disrupt the interaction between ULK1 and TRAF6, profoundly impairs K63-linked polyubiquitination of ULK1 and self-association, leading to the decrease of ULK1 stability. Moreover, in vitro and in vivo experiments suggest thatTMEM189deficiency results in the inhibition of tumorigenicity of gastric cancer. Our findings provide a new insight into the molecular regulation of autophagy and laboratory evidence for investigating the physiological and pathological roles of TMEM189.
A noncoding regulatory RNA Gm31932 induces cell cycle arrest and differentiation in melanoma via the miR-344d-3-5p/Prc1 (and Nuf2) axis
Authors: Wang Dan , Chen Jianfei , Li Bohan , Jiang Qingling , Liu Ling , Xia Ziyi , Zheng Qiusheng , Li Minjing , Li Defang
Published: April 2022

Emerging evidence has shown that long non-coding RNAs (lncRNAs) play an important role in inhibiting tumor cell proliferation and inducing differentiation. In this study, integrative analysis of whole transcriptome sequencing data demonstrated that lncRNA-Gm31932 is significantly decreased in all-trans retinoic acid (ATRA)-induced and sodium 4-phenylbutanoate (PB-4)-induced mouse melanoma B16 cells. Silencing lncRNA-Gm31932 could inhibit B16 cell proliferation, with cell cycle arrest at the G0/G1 phase and obvious differentiation characteristics, e.g., increased cell volume, melanin content and tyrosinase (Tyr) activity. Furthermore, a series of experiments (luciferase reporter assay, RNA pull-down assay, and western blotting) showed that lncRNA-Gm3932 down-regulated Prc1 and Nuf2 by competitively sponging miR-344d-3-5p, which subsequently reduced the expression of cell cycle-related proteins CDK2, CDC2, and Cyclin B1, and increased the expression of P21 and P27. Moreover, silencing lncRNA-Gm31932 could significantly inhibit tumor growth in B16 melanoma-bearing mice. Taken together, these results indicate that as a possible signaling pathway for ATRA and PB-4, lncRNA-Gm31932 can induce cell cycle arrest and differentiation via miR-344d-3-5p/Prc1 (and Nuf2) axis.
NiH-catalysed proximal-selective hydroalkylation of unactivated alkenes and the ligand effects on regioselectivity
Authors: Wang Xiao-Xu , Xu Yuan-Tai , Zhang Zhi-Lin , Lu Xi , Fu Yao
Published: April 2022

Alkene hydrocarbonation reactions have been developed to supplement traditional electrophile-nucleophile cross-coupling reactions. The branch-selective hydroalkylation method applied to a broad range of unactivated alkenes remains challenging. Herein, we report a NiH-catalysed proximal-selective hydroalkylation of unactivated alkenes to access β- or γ-branched alkyl carboxylic acids and β-, γ- or δ-branched alkyl amines. A broad range of alkyl iodides and bromides with different functional groups can be installed with excellent regiocontrol and availability for site-selective late-stage functionalization of biorelevant molecules. Under modified reaction conditions with NiCl2(PPh3)2 as the catalyst, migratory hydroalkylation takes place to provide β- (rather than γ-) branched products. The keys to success are the use of aminoquinoline and picolinamide as suitable directing groups and combined experimental and computational studies of ligand effects on the regioselectivity and detailed reaction mechanisms.
A universal deep neural network for in-depth cleaning of single-cell RNA-Seq data
Authors: Li Hui , Brouwer Cory R. , Luo Weijun
Published: April 2022

Single cell RNA sequencing (scRNA-Seq) is being widely used in biomedical research and generated enormous volume and diversity of data. The raw data contain multiple types of noise and technical artifacts, which need thorough cleaning. Existing denoising and imputation methods largely focus on a single type of noise (i.e., dropouts) and have strong distribution assumptions which greatly limit their performance and application. Here we design and develop the AutoClass model, integrating two deep neural network components, an autoencoder, and a classifier, as to maximize both noise removal and signal retention. AutoClass is distribution agnostic as it makes no assumption on specific data distributions, hence can effectively clean a wide range of noise and artifacts. AutoClass outperforms the state-of-art methods in multiple types of scRNA-Seq data analyses, including data recovery, differential expression analysis, clustering analysis, and batch effect removal. Importantly, AutoClass is robust on key hyperparameter settings including bottleneck layer size, pre-clustering number and classifier weight. We have made AutoClass open source at: https://github.com/datapplab/AutoClass.
Assessing the inflammatory response to in vitro polymicrobial wound biofilms in a skin epidermis model
Authors: Brown Jason L. , Townsend Eleanor , Short Robert D. , Williams Craig , Woodall Chris , Nile Christopher J. , Ramage Gordon
Published: April 2022

Wounds can commonly become infected with polymicrobial biofilms containing bacterial and fungal microorganisms. Microbial colonization of the wound can interfere with sufficient healing and repair, leading to high rates of chronicity in certain individuals, which can have a huge socioeconomic burden worldwide. One route for alleviating biofilm formation in chronic wounds is sufficient treatment of the infected area with topical wound washes and ointments. Thus, the primary aim here was to create a complex in vitro biofilm model containing a range of microorganisms commonly isolated from the infected wound milieu. These polymicrobial biofilms were treated with three conventional anti-biofilm wound washes, chlorhexidine (CHX), povidone-iodine (PVP-I), and hydrogen peroxide (H2O2), and efficacy against the microorganisms assessed using live/dead qPCR. All treatments reduced the viability of the biofilms, although H2O2 was found to be the most effective treatment modality. These biofilms were then co-cultured with 3D skin epidermis to assess the inflammatory profile within the tissue. A detailed transcriptional and proteomic profile of the epidermis was gathered following biofilm stimulation. At the transcriptional level, all treatments reduced the expression of inflammatory markers back to baseline (untreated tissue controls). Olink technology revealed a unique proteomic response in the tissue following stimulation with untreated and CHX-treated biofilms. This highlights treatment choice for clinicians could be dictated by how the tissue responds to such biofilm treatment, and not merely how effective the treatment is in killing the biofilm.
Pneumococcal carriage in unvaccinated children at the time of vaccine implementation into the national immunization program in Poland
Authors: Wróbel-Pawelczyk Izabela , Ronkiewicz Patrycja , Wanke-Rytt Monika , Rykowska Dominika , Górska-Kot Aneta , Włodkowska Katarzyna , Topczewska-Cabanek Agnieszka , Jackowska Teresa , Chruszcz Joanna , Marchut Walentyna , Mastalerz-Migas Agnieszka , Korzeniewski Krzysztof ,   GIL Study Team, Gastoł Karolina , Gromek Marta , Jankowska-Sasin Katarzyna , Karpierz Katarzyna , Okarska-Napierała Magdalena , Pokorna-Kałwak Dagmara , Polit Agata , Robakiewicz Julia , Rygalski Maciej , Siwonia Anna , Strzałka Martyna , Szenborn Leszek , Szwejkowska Martyna , Szymańska-Toczek Zofia , Zaleska Izabela , Żołnierowicz Katarzyna , Skoczyńska Anna , Trzciński Krzysztof
Published: April 2022

We investigated pneumococcal carriage among unvaccinated children under five years of age at a time when the conjugate polysaccharide vaccine (PCV) was introduced in Poland into the national immunization program (NIP). Paired nasopharyngeal swab (NPS) and saliva samples collected between 2016 and 2020 from n = 394 children were tested with conventional culture and using qPCR. The carriage rate detected by culture was 25.4% (97 of 394), by qPCR 39.1% (155 of 394), and 40.1% (158 of 394) overall. The risk of carriage was significantly elevated among day care center attendees, and during autumn/winter months. Among isolates cultured, the most common serotypes were: 23A, 6B, 15BC, 10A, 11A. The coverage of PCV10 and PCV13 was 23.2% (23 of 99) and 26.3% (26 of 99), respectively. Application of qPCR lead to detection of 168 serotype carriage events, with serogroups 15, 6, 9 and serotype 23A most commonly detected. Although the highest number of carriers was identified by testing NPS with qPCR, saliva significantly contributed to the overall number of detected carriers. Co-carriage of multiple serotypes was detected in 25.3% (40 of 158) of carriers. The results of this study represent a baseline for the future surveillance of effects of pneumococcal vaccines in NIP in Poland.
The influence of soil dry-out on the record-breaking hot 2013/2014 summer in Southeast Brazil
Authors: Geirinhas J. L. , Russo A. C. , Libonati R. , Miralles D. G. , Sousa P. M. , Wouters H. , Trigo R. M.
Published: April 2022

The 2013/2014 summer in Southeast Brazil was marked by historical unprecedented compound dry and hot (CDH) conditions with profound socio-economic impacts. The synoptic drivers for this event have already been analyzed, and its occurrence within the context of the increasing trend of CDH conditions in the area evaluated. However, so far, the causes for these record temperatures remain poorly understood. Here, a detailed characterization of the 2013/2014 austral summer season over Southeast Brazil is proposed, emphasizing the role played by land–atmosphere interactions in temperature escalation. We demonstrate that a strong soil moisture–temperature coupling regime promoted record-breaking temperatures levels exceeding almost 5 °C over the previous highest record, and played a key role in triggering an outstanding ‘mega-heatwave’ that lasted for a period of around 20 days. This pronounced soil desiccation occurred within a current climate change trend defined by drier and hotter conditions in the region. The soil dry-out, coupled with strong radiative processes and low entrainment of cooler air masses through mesoscale sea-breeze circulation processes, led to a water-limited regime and to an enhancement of sensible heat fluxes that, ultimately, resulted in a sharp increase of surface temperatures.
Characterization of spatiotemporal electroactive anodic biofilm activity distribution using 1D simulations
Authors: Belleville Pierre , Merlin Gerard , Ramousse Julien , Deseure Jonathan
Published: April 2022

Activity distribution limitation in electroactive biofilm remains an unclear phenomenon. Some observations using confocal microscopy have shown notable difference between activity close to the anode and activity at the liquid interface. A numerical model is developed in this work to describe biofilm growth and local biomass segregation in electroactive biofilm. Under our model hypothesis, metabolic activity distribution in the biofilm results from the competition between two limiting factors: acetate diffusion and electronic conduction in the biofilm. Influence of inactive biomass fraction (i.e. non-growing biomass fraction) properties (such as conductivity and density) is simulated to show variation in local biomass distribution. Introducing a dependence of effective diffusion to local density leads to a drastic biomass fraction segregation. Increasing density of inactive fraction reduces significantly acetate diffusion in biofilm, enhances biomass activity on the outer layer (liquid/biofilm interface) and maintains inner core largely inactive. High inactive fraction conductivity enhances biomass activity in the outer layer and enhances current production. Hence, investment in extracellular polymer substance (EPS), anchoring redox components, is benefit for biofilm electroactivity. However, under our model hypothesis it means that conductivity should be two order lower than biofilm conductivity reported in order to observe inner core active biomass segregation.
Prediction of treatment outcome in neovascular age-related macular degeneration using a novel convolutional neural network
Authors: Yeh Tsai-Chu , Luo An-Chun , Deng Yu-Shan , Lee Yu-Hsien , Chen Shih-Jen , Chang Po-Han , Lin Chun-Ju , Tai Ming-Chi , Chou Yu-Bai
Published: April 2022

While prognosis and risk of progression are crucial in developing precise therapeutic strategy in neovascular age-related macular degeneration (nAMD), limited predictive tools are available. We proposed a novel deep convolutional neural network that enables feature extraction through image and non-image data integration to seize imperative information and achieve highly accurate outcome prediction. The Heterogeneous Data Fusion Net (HDF-Net) was designed to predict visual acuity (VA) outcome (improvement ≥ 2 line or not) at 12th months after anti-VEGF treatment. A set of pre-treatment optical coherence tomography (OCT) image and non-image demographic features were employed as input data and the corresponding 12th-month post-treatment VA as the target data to train, validate, and test the HDF-Net. This newly designed HDF-Net demonstrated an AUC of 0.989 (95% CI 0.970–0.999), accuracy of 0.936 [95% confidence interval (CI) 0.889–0.964], sensitivity of 0.933 (95% CI 0.841–0.974), and specificity of 0.938 (95% CI 0.877–0.969). By simulating the clinical decision process with mixed pre-treatment information from raw OCT images and numeric data, HDF-Net demonstrated promising performance in predicting individualized treatment outcome. The results highlight the potential of deep learning to simultaneously process a broad range of clinical data to weigh and leverage the complete information of the patient. This novel approach is an important step toward real-world personalized therapeutic strategy for typical nAMD.
Individual treatment effect estimation in the presence of unobserved confounding using proxies: a cohort study in stage III non-small cell lung cancer
Authors: van Amsterdam Wouter A. C. , Verhoeff Joost. J. C. , Harlianto Netanja I. , Bartholomeus Gijs A. , Puli Aahlad Manas , de Jong Pim A. , Leiner Tim , van Lindert Anne S. R. , Eijkemans Marinus J. C. , Ranganath Rajesh
Published: April 2022

Randomized Controlled Trials (RCT) are the gold standard for estimating treatment effects but some important situations in cancer care require treatment effect estimates from observational data. We developed “Proxy based individual treatment effect modeling in cancer” (PROTECT) to estimate treatment effects from observational data when there are unobserved confounders, but proxy measurements of these confounders exist. We identified an unobserved confounder in observational cancer research: overall fitness. Proxy measurements of overall fitness exist like performance score, but the fitness as observed by the treating physician is unavailable for research. PROTECT reconstructs the distribution of the unobserved confounder based on these proxy measurements to estimate the treatment effect. PROTECT was applied to an observational cohort of 504 stage III non-small cell lung cancer (NSCLC) patients, treated with concurrent chemoradiation or sequential chemoradiation. Whereas conventional confounding adjustment methods seemed to overestimate the treatment effect, PROTECT provided credible treatment effect estimates.
Mutational scanning of spike RBD protein for enhanced ACE2 affinity emerging Southeast Asia in the late transmission phase
Authors: Kodchakorn Kanchanok , Chokepaichitkool Tawan , Kongtawelert Prachya
Published: April 2022

The COVID-19 pandemic has changed the quality of life and economic systems all over the world, as the virus can be transmitted from human to human via air-droplets. Since the SARS-CoV-2 virus was first identified in 2019, the virus has naturally mutated over time. Southeast Asia is one of the areas in the world that has implemented various procedures and measures to slow down the disease outbreaks. The first cluster of COVID-19 was identified from the tourist-travel history, and then the diversity of coronavirus victims has posed a serious issue of human security on a massive scale. To evaluate whether or not naturally occurring mutations have strengthened the infectivity of SARS-CoV-2, we computed in silico the structural dynamics of the RBD-spike protein mutation enhancing ACE2-binding. When considering emerging variations in Southeast Asia, 14 dominant mutations were analyzed by applying the structural and energetic characterization using MD simulations. The ones in the RBD region displayed higher affinity to ACE2 due to the improved interfacial stability of the RBD β-strand surrounding the ACE2 across salt bridge hotspots. The binding hotspots and structurally conserved conformational-epitopes have been identified, which are deleterious for RBD mutation and ACE2 binding. We present an interactive visualization to facilitate the development of effective neutralizing agents for vaccination, prevention and treatment.