bluuebunny/crossref_metadata_2025 huggingface dataset:
An ultra-lightweight efficient network for image-based plant disease and pest infection detection
Authors: Wang Beibei , Zhang Chenxiao , Li Yanyan , Cao Chunxia , Huang Daye , Gong Yan
Published: April 2023

Plant diseases and pest infections are major factors that undermine the growth of plants along with their life cycle. Optical image-based plant disease detection provides an efficient and low cost way for real-time plant growth monitoring and management. In recent years, the thriving development of deep learning techniques in a variety of communities has validated its great performance in image interpretation and understanding. Existing deep learning-based methods for plant disease classification mostly adopt convolutional neural networks (CNNs) that have been originally developed for general image classification purposes. These CNN architectures consist of a very large volume of training parameters, which severely hinders its applicability under scenarios requiring fast and flexible deployment on compact devices with limited computation powers. In this paper, an ultra-lightweight efficient network (ULEN) is proposed targeting image-based plant disease and pest infection detection. The proposed network consists of two parts, a deep feature extraction module that adopts residual depth-wise convolution and a classification module receiving multi-scale features enhanced by a spatial pyramid pooling layer. The network is constructed in a very compact design with approximately only 100 000 parameters, which greatly favors the demand for a lightweight model for practical needs. Two publicly available plant datasets collected at the indoor and outdoor environments were tested on two compact devices to validate its applicability under different scenarios. Compared with the state-of-the-art architectures, the proposed network showed superior performance with the least computation complexity and compelling classification accuracy.
Tracking Home-Owners’ Sentiments: Subjective Indices and Convergent Validity
Authors: Waltl Sofie R. , Lepinteur Anthony
Published: April 2023

Surveys regularly ask home-owners to guess what their property might be worth in the current housing market. We develop suitable statistical techniques to construct hedonic and repeat-sales style house price indices from these owner-estimated values (OEVs). The resulting series are then linked to a large set of quality-adjusted residential property price indices estimated from transaction data allowing us to perform a variety of convergent validity tests. Based on results for 20 countries, several decades and different OEV elicitation techniques, we conclude that the“wisdom of the home-owner crowd”is sufficient to study objective house price dynamics. Yet, surveys fail to accurately measure house price levels.
Consumption and income expectations during Covid-19
Authors: Immordino Giovanni , Jappelli Tullio , Oliviero Tommaso
Published: April 2023

Using a survey of Italian households administered in November 2021, we study the effect of microeconomic and macroeconomic expectations about the health crisis and income growth on consumption expectations in 2022. The survey elicits individual-level indicators of income and consumption expectations, distinguishing between consumption at home, away from home, online and total. We find that expected household income and expected GDP growth are strongly related to consumption expectations; income risk is positively associated with expected consumption growth for richer households. Finally, our results indicate that health-related variables were not a major drivers of consumption expectations in 2022.
Activation of telomerase by TA-65 enhances immunity and reduces inflammation post myocardial infarction
Authors: Bawamia Bilal , Spray Luke , Wangsaputra Vincent K. , Bennaceur Karim , Vahabi Sharareh , Stellos Konstantinos , Kharatikoopaei Ehsan , Ogundimu Emmanuel , Gale Chris P. , Keavney Bernard , Maier Rebecca , Hancock Helen , Richardson Gavin , Austin David , Spyridopoulos Ioakim
Published: April 2023

Myocardial infarction (MI) accelerates immune ageing characterised by lymphopenia, expansion of terminally differentiated CD8+ T-lymphocytes (CD8+ TEMRA) and inflammation. Pre-clinical data showed that TA-65, an oral telomerase activator, reduced immune ageing and inflammation after MI. We conducted a double blinded randomised controlled pilot trial evaluating the use of TA-65 to reduce immune cell ageing in patients following MI. Ninety MI patients aged over 65 years were randomised to either TA-65 (16 mg daily) or placebo for 12 months. Peripheral blood leucocytes were analysed by flow cytometry. The pre-defined primary endpoint was the proportion of CD8+ T-lymphocytes which were CD8+ TEMRA after 12 months. Secondary outcomes included high-sensitivity C-reactive protein (hsCRP) levels. Median age of participants was 71 years. Proportions of CD8+ TEMRA did not differ after 12 months between treatment groups. There was a significant increase in mean total lymphocyte count in the TA-65 group after 12 months (estimated treatment effect: + 285 cells/μl (95% CI: 117–452 cells/ μ l, p < 0.004), driven by significant increases from baseline in CD3+, CD4+, and CD8+ T-lymphocytes, B-lymphocytes and natural killer cells. No increase in lymphocyte populations was seen in the placebo group. At 12 months, hsCRP was 62% lower in the TA-65 group compared to placebo (1.1 vs. 2.9 mg/L). Patients in the TA-65 arm experienced significantly fewer adverse events (130 vs. 185, p = 0.002). TA-65 did not alter CD8+ TEMRA but increased all major lymphocyte subsets and reduced hsCRP in elderly patients with MI after 12 months.
Genetic perturbation of mitochondrial function reveals functional role for specific mitonuclear genes, metabolites, and pathways that regulate lifespan
Authors: Phua Cheryl Zi Jin , Zhao Xiaqing , Turcios-Hernandez Lesly , McKernan Morrigan , Abyadeh Morteza , Ma Siming , Promislow Daniel , Kaeberlein Matt , Kaya Alaattin
Published: April 2023

Altered mitochondrial function is tightly linked to lifespan regulation, but underlying mechanisms remain unclear. Here, we report the chronological and replicative lifespan variation across 167 yeast knock-out strains, each lacking a single nuclear-coded mitochondrial gene, including 144 genes with human homologs, many associated with diseases. We dissected the signatures of observed lifespan differences by analyzing profiles of each strain’s proteome, lipidome, and metabolome under fermentative and respiratory culture conditions, which correspond to the metabolic states of replicative and chronologically aging cells, respectively. Examination of the relationships among extended longevity phenotypes, protein, and metabolite levels revealed that although many of these nuclear-encoded mitochondrial genes carry out different functions, their inhibition attenuates a common mechanism that controls cytosolic ribosomal protein abundance, actin dynamics, and proteasome function to regulate lifespan. The principles of lifespan control learned through this work may be applicable to the regulation of lifespan in more complex organisms, since many aspects of mitochondrial function are highly conserved among eukaryotes.
Gene Drives as Interventions into Nature: the Coproduction of Ontology and Morality in the Gene Drive Debate
Authors: Boersma Keje , Bovenkerk Bernice , Ludwig David
Published: April 2023

Gene drives are potentially ontologically and morally disruptive technologies. The potential to shape evolutionary processes and to eradicate (e.g. malaria-transmitting or invasive) populations raises ontological questions about evolution, nature, and wilderness. The transformative promises and perils of gene drives also raise pressing ethical and political concerns. The aim of this article is to arrive at a better understanding of the gene drive debate by analysing how ontological and moral assumptions are coproduced in this debate. Combining philosophical analysis with a critical reading of the gene drive literature and an ethnographic study of two leading research groups, the article explores the hypothesis that the development of and debate about gene drives are characterized by a particular intervention-oriented mode of coproduction. Based on the results of this exploration, we highlight the need for a broadening of the perspective on gene drives in which empirical, moral, and ontological concerns are addressed explicitly in their interplay rather than in (disciplinary) isolation from each other.
Modifying the Environment or Human Nature? What is the Right Choice for Space Travel and Mars Colonisation?
Authors: Balistreri Maurizio , Umbrello Steven
Published: April 2023

As space travel and intentions to colonise other planets are becoming the norm in public debate and scholarship, we must also confront the technical and survival challenges that emerge from these hostile environments. This paper aims to evaluate the various arguments proposed to meet the challenges of human space travel and extraterrestrial planetary colonisation. In particular, two primary solutions have been present in the literature as the most straightforward solutions to the rigours of extraterrestrial survival and flourishing: (1) geoengineering, where the environment is modified to become hospitable to its inhabitants, and (2) human (bio)enhancement where the genetic heritage of humans is modified to make them more resilient to the difficulties they may encounter as well as to permit them to thrive in non-terrestrial environments. Both positions have strong arguments supporting them but also severe philosophical and practical drawbacks when exposed to different circumstances. This paper aims to show that a principled stance where one position is accepted wholesale necessarily comes at the opportunity cost of the other where the other might be better suited, practically and morally. This paper concludes that case-by-case evaluations of the solutions to space travel and extraterrestrial colonisation are necessary to ensure moral congruency and the survival and flourishing of astronauts now and into the future.
Influence of Bariatric Surgery on Erectile Dysfunction—a Systematic Review and Meta-Analysis
Authors: Małczak Piotr , Wysocki Michał , Pisarska-Adamczyk Magdalena , Strojek Jakub , Rodak Hanna , Lastovetskyi Ilie , Pędziwiatr Michał , Major Piotr
Published: April 2023

Introduction

Obesity is associated with a higher prevalence of various comorbidities including erectile dysfunction (ED). Bariatric surgery leads to weight loss and remission of weight-related diseases. The exact influence of bariatric treatment on ED is yet to be established; however, the number of papers on the subject is growing.

Methodology

A systematic review with meta-analysis comparing erectile dysfunction before and after surgery was conducted according to PRISMA guidelines with a literature search performed in June 2022. Inclusion criteria involved (1) ED assessment using the International International Index of Erectile Function (IIEF) and (2) longitudinal study design. Secondary endpoints involved hormonal changes and specific fields of IIEF.

Results

An initial search yielded 878 records. Fourteen studies were included in the meta-analysis involving 508 patients. The quality of analyzed studies was moderate. Analysis showed significant differences in IIEF before and after surgery (Std. MD = 1.19, 95% CI 0.72 to 1.66, p<0.0001). Testosterone after surgery is higher by 156.32 pg/ml (95% CI 84.78 to 227.86, p<0.0001). There were differences in erectile function (MD:4.86, p < 0.0001), desire (MD: 1.21, p < 0.0001), intercourse satisfaction (MD: 2.16, p < 0.0001), and overall satisfaction (MD: 1.21, p = 0.003). There were no differences in terms of orgasms (MD: 0.65, p = 0.06).

Conclusion

There are differences in ED before and after bariatric surgery. Patients achieve 19% more in the IIEF questionnaire showing improvement. Further studies, including multivariate regression models on large cohorts, are required to determine whether the surgery is an independent factor in alleviating ED.

Graphical Abstract
Appropriateness of packed red blood cells transfusions in chronic anemic patients in the emergency department: the TRANSFUS-ED retrospective analysis
Authors: Paganini Matteo , Rigon Fabio , Rebustello Federico , Cianci Vito , Bertozzi Irene , Randi Maria Luigia
Published: April 2023

Patients suffering from chronic anemia can benefit from scheduled transfusions of packed red blood cells (PRBCs), while urgent transfusions have specific indications. These patients frequently seek medical attention in the emergency department (ED), where they can be inappropriately transfused, but research in this field is limited. This study aimed to assess the appropriateness of PRBCs transfusions in chronic anemic patients in the ED. A retrospective analysis was performed on patients who accessed the ED of the Azienda Ospedaliera di Padova (Padova, Italy) between 2016 and 2019 and received PRBCs transfusions. Patients aged ≥ 18 years old and with chronic anemia were included, while those with acute anemia or admitted to the hospital after the transfusion were excluded. Chronic anemia was defined as satisfying one of the following in the past medical history: diagnosis of chronic anemia; two or more previous blood samplings demonstrating anemia; periodic transfusions. As primary outcome, the appropriateness of transfusions was assessed according to the American Association of Blood Banks (AABB) 2016 criteria, using the recommended threshold of 7 g/dL for hemodynamically stable adults and 8 g/dL for patients with pre-existing cardiovascular disease. Out of 1153 transfusions, 344 transfusions were included in the study. According to our criteria, 139 (40.4%) patients were inappropriately transfused, resulting in a total estimated cost of 54,528.71 € in the study period. This study showed that transfusions in chronic anemic patients are recurrent events in the ED and are frequently inappropriate. A possible explanation could be the lack of a well-structured primary care network granting periodic transfusions in ambulatory centers. In the future, implementing and improving chronic anemic patients’ access to transfusion services through dedicated pathways could reduce the burden on the ED and also decrease costs.
Pathophysiological Links Between Obesity and Dementia
Authors: Wong Zhang David E. , Tran Vivian , Vinh Antony , Dinh Quynh Nhu , Drummond Grant R. , Sobey Christopher G. , Jelinic Maria , De Silva T. Michael
Published: April 2023

Obesity is a major global health concern, with prevalence rates rapidly rising due to increased availability of highly processed foods rich in fats and/or sugars and technological advances promoting more sedentary behaviour. There is increasing evidence to suggest that obesity predisposes individuals to developing cognitive impairment and dementia. However, the relationship between the brain and the peripheral metabolic state is complex, and many of the underlying mechanisms of cognitive impairment in obesity are yet to be fully elucidated. To better understand the links between obesity and dementia, further work is required to determine pathological changes occurring in the brain during obesity. In this mini-review, we discuss the role of two pathological features of obesity (the gut-brain axis and systemic inflammation) and their potential contribution to dementia.
How cost-efficient is energy efficiency in buildings? A comparison of building shell efficiency and heating system change in the European building stock
Authors: Hummel M. , Müller A. , Forthuber S. , Kranzl L. , Mayr B. , Haas R.
Published: April 2023

Mitigating CO2 emissions for space heating (SH) and hot water (HW) preparation in buildings is key to reaching climate protection targets. In this context, it is important to understand meaningful balances between CO2 reduction through thermal renovation activities and the change of heating systems. In this work, we develop cost-optimal balances for different system settings with the Invert/Opt model. This model optimises the measures applied in each building so that the system costs for SH and HW preparation are minimised under given constraints for a given country. About 500–1000 options are considered for each building. We calculate scenarios and sensitivities for all countries of EU-27, reflecting a 95% reduction in CO2 emissions for SH and HW with a mix of direct and indirect RES technologies. These differ in the settings related to the applicability and costs of building-shell-related measures and the costs and availability of resource potentials. The results show that probably a high share of thermal renovation on total upcoming refurbishment activities until 2050 is cost-efficient to reach a 95% CO2 reduction in the EU-27 building stocks. Assuming that up to 90% of the buildings in each EU-27 country is applicable for a thermal renovation in case a refurbishment activity is needed leads to around 4% lower system costs by 2050 (13 billion EUR/year) compared to assuming a maximum share of 35%. Energy needs are reduced on average more in older buildings than in newer buildings. Nonetheless, a combination of thermal renovation and heating system change is often the most cost-effective option to reduce system-wide CO2 emissions also in more recent buildings. The calculations lead to cost-optimal savings in final energy demand in the range of 29–47% between 2019 and 2050. Assuming less favourable conditions for thermal renovation (high capital recovery expectations, additional technical barriers and high availability of cheap fuels) the cost-optimal level of heat savings in buildings for overall EU-27 could be suspected at around 1/3 down to 1/4 of current final energy demand.
Coexistence in spatiotemporally fluctuating environments
Authors: Johnson Evan C. , Hastings Alan
Published: April 2023

Ecologists have put forward many explanations for coexistence, but these are onlypartial explanations; nature is complex, so it is reasonable to assume that in any given ecological community, multiple mechanisms of coexistence are operating at the same time. Here, we present a methodology for quantifying the relative importance of different explanations for coexistence, based on an extension of theModern Coexistence Theory. Current versions of Modern Coexistence Theory only allow for the analysis of communities that are affected by spatialortemporal environmental variation, but not both. We show how to analyze communities with spatiotemporal fluctuations, how to parse the importance of spatial variation and temporal variation, and how to measure everything with either mathematical expressions or simulation experiments. Our extension of Modern Coexistence Theory shows that many more species can coexist than originally thought. More importantly, it allows empiricists to use realistic models and more data to better infer the mechanisms of coexistence in real communities.
The impact of cultural intelligence on burnout among practitioners working with migrants: an examination of age, gender, training, and language proficiency
Authors: Puzzo Gabriele , Sbaa Maha Yomn , Zappalà Salvatore , Pietrantoni Luca
Published: April 2023

Migrants are a vulnerable population that often requires specialized care and support. Practitioners who work with migrants must be knowledgeable about the unique challenges they face. Some first-line practitioners are better equipped to work in intercultural environments because they possess higher cultural intelligence (CQ). This study aims to examine the impact of cultural intelligence on burnout among practitioners working in 15 countries. It also compares levels of CQ in relation to age, gender, education, intercultural training, and language proficiency in the workplace. The participants in the study were professionals working primarily with migrants (N = 258) from 15 countries. The results indicate that motivational cultural intelligence significantly reduces burnout levels, while the cognitive and the behavioural dimensions do not have any effect. Practitioners who have undergone intercultural training have higher levels of cultural intelligence, and this type of training may be effective in improving cultural intelligence. The study provides organizations with insight on how to select and train first-line practitioners, focusing on developing cultural competencies and intrinsic motivation to prevent burnout among their staff and ultimately improve the quality of services.
Factors Explaining Workplace Learning of Turkish Research Assistants
Authors: Alkan Muhammet Fatih , Emmioğlu-Sarıkaya Esma
Published: April 2023

The purpose of this study was to explore the structural relationships among diverse variables to provide a comprehensive understanding of Turkish research assistants’ workplace learning. The cross-sectional data of the study were collected online from 21 universities around Turkey. A total of 1218 research assistants from various disciplines took part in the study. The findings revealed that workplace affordances as well as the personal factors of workplace effort and personal agency had direct, positive, and statistically significant effects on the workplace learning of research assistants. The rest of the personal factors including vocational identity, workplace identity, and interpersonal agency had statistically significant direct effects on workplace affordances. Moreover, these three personal factors had statistically significant indirect effects on workplace learning. These findings showed that research assistants’ workplace learning was impacted by both what the workplaces offered and how the research assistants perceived these affordances. The findings also showed that some of the personal variables affected workplace learning independent of workplace affordances.
POLG2-Linked Mitochondrial Disease: Functional Insights from New Mutation Carriers and Review of the Literature
Authors: Borsche Max , Dulovic-Mahlow Marija , Baumann Hauke , Tunc Sinem , Lüth Theresa , Schaake Susen , Özcakir Selin , Westenberger Ana , Münchau Alexander , Knappe Evelyn , Trinh Joanne , Brüggemann Norbert , Lohmann Katja
Published: April 2023

Different pathogenic variants in the DNA polymerase-gamma2 (POLG2) gene cause a rare, clinically heterogeneous mitochondrial disease. We detected a novel POLG2 variant (c.1270 T > C, p.Ser424Pro) in a family with adult-onset cerebellar ataxia and progressive ophthalmoplegia. We demonstrated altered mitochondrial integrity in patients’ fibroblast cultures but no changes of the mitochondrial DNA were found when compared to controls. We consider this novel, segregating POLG2 variant as disease-causing in this family. Moreover, we systematically screened the literature for POLG2-linked phenotypes and re-evaluated all mutations published to date for pathogenicity according to current knowledge. Thereby, we identified twelve published, likely disease-causing variants in 19 patients only. The core features included progressive ophthalmoplegia and cerebellar ataxia; parkinsonism, neuropathy, cognitive decline, and seizures were also repeatedly found in adult-onset heterozygous POLG2-related disease. A severe phenotype relates to biallelic pathogenic variants in POLG2, i.e., newborn-onset liver failure, referred to as mitochondrial depletion syndrome. Our work underlines the broad clinical spectrum of POLG2-related disease and highlights the importance of functional characterization of variants of uncertain significance to enable meaningful genetic counseling.
Intrauterine Administration of Autologous Platelet-Derived Growth Factor Concentrate (aka Autologous Blood Cell Derivative) Improves the Endometrial Thickness in 'Thin' Endometrium in the Frozen Embryo Transfer Cycle
Authors: Kumar Pratap , Mundkur Anjali , Sai Bhavna D. , Palanivel Vasanthi , Adiga Prashanth , Poojari Vidyashree G. , Rao Shubha , Ullagaddi Rashmi
Published: April 2023

Abstracts

Context

Thin endometrium during the frozen embryo transfer cycles leads to cycle cancellation. The embryo transfer cycle getting deferred is an unpleasant experience for the patients and the fertility specialist.

Aims

The purpose of this study is to evaluate the effectiveness of Autologous Blood Cell Derivative (ABCD) growth factor concentrate to obtain an optimal thickness of endometrium for embryo transfer during IVF treatments, where rapid regeneration is crucial for the expected therapeutic outcome.

Settings and Design

A retrospective cohort study was conducted in Manipal Assisted Reproduction Center, a referral center in Southern India.

Methods and Material

Fifty-six patients with thin endometrium were administered three doses of ABCD growth factor concentrate as per the protocol after informed consent. All of them had a history of embryo transfer (ET) cancellation in frozen-thawed embryo cycles due to inadequate growth of the endometrium despite therapy with estrogens and drugs for improving uterine blood circulation.

Results

The endometrium thickness during the implantation window in the patients included in the study averaged 6.48 ± 1.19 mm. After the intervention, 55 out of 56 patients (98.2%) showed a considerable change in the thickness of the endometrium layer with an average thickness of 8.48 ± 1.32 mm (< 0.0001, SE 0.233, 95% CI 1.58–2.5). Out of the 55 patients, 20 got pregnant, i.e., 36.4% pregnancy rate. Till date, thirteen pregnancies had live births (65%), three pregnancies (15%) were biochemical pregnancies, 1 (5%) was ectopic, and three pregnancies (15%) had spontaneous miscarriage before eight weeks. When we compared the endometrial thickness (EMT) in the pregnant and non-pregnant groups pre- and post-ABCD instillation, (6.47 ± 1.31 mm vs 6.48 ± 1.4 mm,p = 0.98 and 8.68 ± 1.32 mm vs 8.48 ± 1.32 mm,pvalue 0.59) thepvalue was not statistically significant.

Conclusions

The implantation, clinical pregnancy and live birth rates were 36.4, 30 and 65%, respectively. This result is a significant improvement for patients with thin endometrium for whom we would otherwise cancel the frozen transfer. An autologous resource is a safe, readily available and inexpensive treatment modality.
Role of PET gamma detection in radioguided surgery: a systematic review
Authors: De Feo Maria Silvia , Frantellizzi Viviana , De Sio Luciano , Farcomeni Alessio , De Vincentis Giuseppe , Pani Roberto
Published: April 2023

Purpose

This systematic review aimed to collect published studies concerning intraoperative gamma detection of positron-emitting tracers for radioguided surgery (RGS) applications.

Methods

A systematic literature search of studies published until October 2022 was performed in Pubmed, Web Of Science, Central (Cochrane Library) and Scopus databases, including the following keywords: “Positron Emission Tomography” OR “PET” AND “Gamma” OR “γ” AND “Probe” AND “Radioguided Surgery” OR “RGS”. The included studies had to concern RGS procedures performed in at least 3 patients, regardless of the administered radiopharmaceutical and the field of application.

Results

Among to the 17 selected studies, all published between 2000 and 2022, only 2 investigations were conducted with gallium-68 (68Ga)-labeled somatostatin analogues, with fluorine-18-fluoro-2-deoxyglucose ([18F]FDG) being the most commonly used agent for RGS applications. Almost all studies were performed in oncologic patients, with only one paper also including inflammatory and infectious findings. The analysis showed that the largest part of procedures was performed through the intraoperative use of conventional gamma probes, not specifically designed for the detection of annihilation photons (n = 9), followed by PET gamma probes (n = 5) and with only three studies involving electronic collimation.

Conclusions

Regardless of the intraoperative devices, RGS with positron emitters seems to lead to significant improvements in surgeons’ ability to obtain a complete resection of tumors, even if the nature of photons resulting from positron–electron collision still remains extremely challenging and requires further technical advances.
Enhancing the earthquake resistance of RC and steel high-rise buildings by bracings, shear walls and TMDs considering SSI
Authors: Kontoni Denise-Penelope N. , Farghaly Ahmed Abdelraheem
Published: April 2023

The increasing population, limited residential space, and scarcity of suitable land for construction have led to a rise in the construction of high-rise buildings (HRBs) as a means to provide additional housing. The increase in human activities (such as excavations for geothermal resources) has led to an increase in seismic activity, making HRBs more vulnerable to earthquakes. Structural analysis of HRBs that are exposed to seismic loadings depends on one of the most important factors that judge the stability and resistance to seismic waves which is the stiffness of the buildings. Various methods that reduce flexibility and enhance stiffness for HRBs are the subject of this numerical investigation, and they were applied to a high-rise building (HRB) of 20 floors, considering soil–structure interaction (SSI). The stiffening methods adopted herein are steel or concrete shear walls (SWs) in specific arrangements, and different bracings in specific arrangements. Moreover, in this study, tuned mass dampers (TMDs) are used, as a damping method of the HRB seismic response, also considering SSI, and the results are compared with the stiffening methods results to judge how the applied methods enhance the seismic resistance of HRBs. These methods, which were used to influence the stiffness or the damping of the building, had different positive effects on the seismic response of the HRBs, which appeared in the results through the base shears, the base moments, the maximum top displacement, and the fundamental period of the building.
Climate Change Knocks It Out of the Park
Authors: Cartier Kimberly
Published: April 2023

A climate curve ball: Short-term gains in home runs might soon give way to long-term problems when it gets too hot to play.
TMIGD1: Emerging functions of a tumor supressor and adhesion receptor
Authors: Thüring Eva-Maria , Hartmann Christian , Schwietzer Ysabel A. , Ebnet Klaus
Published: April 2023

The development of multicellular organisms depends on cell adhesion molecules (CAMs) that connect cells to build tissues. The immunoglobulin superfamily (IgSF) constitutes one of the largest families of CAMs. Members of this family regulate such diverse processes like synapse formation, spermatogenesis, leukocyte-endothelial interactions, or epithelial cell-cell adhesion. Through their extracellular domains, they undergo homophilic and heterophilic interactions in cis and trans. Their cytoplasmic domains frequently bind scaffolding proteins to assemble signaling complexes. Transmembrane and immunoglobulin domain-containing protein 1 (TMIGD1) is a IgSF member with two Ig-like domains and a short cytoplasmic tail that contains a PDZ domain-binding motif. Recent observations indicate that TMIGD1 has pleiotropic functions in epithelial cells and has a critical role in suppressing malignant cell behavior. Here, we review the molecular characteristics of TMIGD1, its interaction with cytoplasmic scaffolding proteins, the regulation of its expression, and its downregulation in colorectal and renal cancers.
Cntnap4 partial deficiency exacerbates α-synuclein pathology through astrocyte–microglia C3-C3aR pathway
Authors: Zhang Wenlong , Ding Liuyan , Chen Huaqing , Zhang Mengran , Ma Runfang , Zheng Shaohui , Gong Junwei , Zhang Zhiling , Xu Huaxi , Xu Pingyi , Zhang Yunlong
Published: April 2023

Parkinson’s disease (PD) is the most common progressive neurodegenerative movement disorder, which is characterized by dopaminergic (DA) neuron death and the aggregation of neurotoxic α-synuclein. Cntnap4, a risk gene of autism, has been implicated to participate in PD pathogenesis. Here we showed Cntnap4 lacking exacerbates α-synuclein pathology, nigrostriatal DA neuron degeneration and motor impairment, induced by injection of adeno-associated viral vector (AAV)-mediated human α-synuclein overexpression (AAV-hα-Syn). This scenario was further validated in A53T α-synuclein transgenic mice injected with AAV-Cntnap4 shRNA. Mechanistically, α-synuclein derived from damaged DA neuron stimulates astrocytes to release complement C3, activating microglial C3a receptor (C3aR), which in turn triggers microglia to secrete complement C1q and pro-inflammatory cytokines. Thus, the astrocyte–microglia crosstalk further drives DA neuron death and motor dysfunction in PD. Furthermore, we showed that in vivo depletion of microglia and microglial targeted delivery of a novel C3aR antagonist (SB290157) rescue the aggravated α-synuclein pathology resulting from Cntnap4 lacking. Together, our results indicate that Cntnap4 plays a key role in α-synuclein pathogenesis by regulating glial crosstalk and may be a potential target for PD treatment.
Rhinovirus-induced epithelial RIG-I inflammasome suppresses antiviral immunity and promotes inflammation in asthma and COVID-19
Authors: Radzikowska Urszula , Eljaszewicz Andrzej , Tan Ge , Stocker Nino , Heider Anja , Westermann Patrick , Steiner Silvio , Dreher Anita , Wawrzyniak Paulina , Rückert Beate , Rodriguez-Coira Juan , Zhakparov Damir , Huang Mengting , Jakiela Bogdan , Sanak Marek , Moniuszko Marcin , O’Mahony Liam , Jutel Marek , Kebadze Tatiana , Jackson David J. , Edwards Michael R. , Thiel Volker , Johnston Sebastian L. , Akdis Cezmi A. , Sokolowska Milena
Published: April 2023

Rhinoviruses and allergens, such as house dust mite are major agents responsible for asthma exacerbations. The influence of pre-existing airway inflammation on the infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is largely unknown. We analyse mechanisms of response to viral infection in experimental in vivo rhinovirus infection in healthy controls and patients with asthma, and in in vitro experiments with house dust mite, rhinovirus and SARS-CoV-2 in human primary airway epithelium. Here, we show that rhinovirus infection in patients with asthma leads to an excessive RIG-I inflammasome activation, which diminishes its accessibility for type I/III interferon responses, leading to their early functional impairment, delayed resolution, prolonged viral clearance and unresolved inflammation in vitro and in vivo. Pre-exposure to house dust mite augments this phenomenon by inflammasome priming and auxiliary inhibition of early type I/III interferon responses. Prior infection with rhinovirus followed by SARS-CoV-2 infection augments RIG-I inflammasome activation and epithelial inflammation. Timely inhibition of the epithelial RIG-I inflammasome may lead to more efficient viral clearance and lower the burden of rhinovirus and SARS-CoV-2 infections.
Improved photovoltaic performance and robustness of all-polymer solar cells enabled by a polyfullerene guest acceptor
Authors: Yu Han , Wang Yan , Zou Xinhui , Yin Junli , Shi Xiaoyu , Li Yuhao , Zhao Heng , Wang Lingyuan , Ng Ho Ming , Zou Bosen , Lu Xinhui , Wong Kam Sing , Ma Wei , Zhu Zonglong , Yan He , Chen Shangshang
Published: April 2023

Fullerene acceptors typically possess excellent electron-transporting properties and can work as guest components in ternary organic solar cells to enhance the charge extraction and efficiencies. However, conventional fullerene small molecules typically suffer from undesirable segregation and dimerization, thus limiting their applications in organic solar cells. Herein we report the use of a poly(fullerene-alt-xylene) acceptor (PFBO-C12) as guest component enables a significant efficiency increase from 16.9% for binary cells to 18.0% for ternary all-polymer solar cells. Ultrafast optic and optoelectronic studies unveil that PFBO-C12 can facilitate hole transfer and suppress charge recombination. Morphological investigations show that the ternary blends maintain a favorable morphology with high crystallinity and smaller domain size. Meanwhile, the introduction of PFBO-C12 reduces voltage loss and enables all-polymer solar cells with excellent light stability and mechanical durability in flexible devices. This work demonstrates that introducing polyfullerenes as guest components is an effective approach to achieving highly efficient ternary all-polymer solar cells with good stability and mechanical robustness.
Siglec-6 mediates the uptake of extracellular vesicles through a noncanonical glycolipid binding pocket
Authors: Schmidt Edward N. , Lamprinaki Dimitra , McCord Kelli A. , Joe Maju , Sojitra Mirat , Waldow Ayk , Nguyen Jasmine , Monyror John , Kitova Elena N. , Mozaneh Fahima , Guo Xue Yan , Jung Jaesoo , Enterina Jhon R. , Daskhan Gour C. , Han Ling , Krysler Amanda R. , Cromwell Christopher R. , Hubbard Basil P. , West Lori J. , Kulka Marianne , Sipione Simonetta , Klassen John S. , Derda Ratmir , Lowary Todd L. , Mahal Lara K. , Riddell Meghan R. , Macauley Matthew S.
Published: April 2023

Immunomodulatory Siglecs are controlled by their glycoprotein and glycolipid ligands. Siglec-glycolipid interactions are often studied outside the context of a lipid bilayer, missing the complex behaviors of glycolipids in a membrane. Through optimizing a liposomal formulation to dissect Siglec–glycolipid interactions, it is shown that Siglec-6 can recognize glycolipids independent of its canonical binding pocket, suggesting that Siglec-6 possesses a secondary binding pocket tailored for recognizing glycolipids in a bilayer. A panel of synthetic neoglycolipids is used to probe the specificity of this glycolipid binding pocket on Siglec-6, leading to the development of a neoglycolipid with higher avidity for Siglec-6 compared to natural glycolipids. This neoglycolipid facilitates the delivery of liposomes to Siglec-6 on human mast cells, memory B-cells and placental syncytiotrophoblasts. A physiological relevance for glycolipid recognition by Siglec-6 is revealed for the binding and internalization of extracellular vesicles. These results demonstrate a unique and physiologically relevant ability of Siglec-6 to recognize glycolipids in a membrane.
Observation of structural switch in nascent SAM-VI riboswitch during transcription at single-nucleotide and single-molecule resolution
Authors: Xue Yanyan , Li Jun , Chen Dian , Zhao Xizhu , Hong Liang , Liu Yu
Published: April 2023

Growing RNAs fold differently as they are transcribed, which modulates their finally adopted structures. Riboswitches regulate gene expression by structural change, which are sensitive to co-transcriptionally structural biology. Here we develop a strategy to track the structural change of RNAs during transcription at single-nucleotide and single-molecule resolution and use it to monitor individual transcripts of the SAM-VI riboswitch (riboSAM) as transcription proceeds, observing co-existence of five states in riboSAM. We report a bifurcated helix in one newly identified state from NMR and single-molecule FRET (smFRET) results, and its presence directs the translation inhibition in our cellular translation experiments. A model is proposed to illustrate the distinct switch patterns and gene-regulatory outcome of riboSAM when SAM is present or absent. Our strategy enables the precise mapping of RNAs’ conformational landscape during transcription, and may combine with detection methods other than smFRET for structural studies of RNAs in general.
IS21 family transposase cleaved donor complex traps two right-handed superhelical crossings
Authors: Spínola-Amilibia Mercedes , Araújo-Bazán Lidia , de la Gándara Álvaro , Berger James M. , Arias-Palomo Ernesto
Published: April 2023

Transposases are ubiquitous enzymes that catalyze DNA rearrangement events with broad impacts on gene expression, genome evolution, and the spread of drug-resistance in bacteria. Here, we use biochemical and structural approaches to define the molecular determinants by which IstA, a transposase present in the widespread IS21 family of mobile elements, catalyzes efficient DNA transposition. Solution studies show that IstA engages the transposon terminal sequences to form a high-molecular weight complex and promote DNA integration. A 3.4 Å resolution structure of the transposase bound to transposon ends corroborates our biochemical findings and reveals that IstA self-assembles into a highly intertwined tetramer that synapses two supercoiled terminal inverted repeats. The three-dimensional organization of the IstA•DNA cleaved donor complex reveals remarkable similarities with retroviral integrases and classic transposase systems, such as Tn7 and bacteriophage Mu, and provides insights into IS21 transposition.
TransPolymer: a Transformer-based language model for polymer property predictions
Authors: Xu Changwen , Wang Yuyang , Barati Farimani Amir
Published: April 2023

Accurate and efficient prediction of polymer properties is of great significance in polymer design. Conventionally, expensive and time-consuming experiments or simulations are required to evaluate polymer functions. Recently, Transformer models, equipped with self-attention mechanisms, have exhibited superior performance in natural language processing. However, such methods have not been investigated in polymer sciences. Herein, we report TransPolymer, a Transformer-based language model for polymer property prediction. Our proposed polymer tokenizer with chemical awareness enables learning representations from polymer sequences. Rigorous experiments on ten polymer property prediction benchmarks demonstrate the superior performance of TransPolymer. Moreover, we show that TransPolymer benefits from pretraining on large unlabeled dataset via Masked Language Modeling. Experimental results further manifest the important role of self-attention in modeling polymer sequences. We highlight this model as a promising computational tool for promoting rational polymer design and understanding structure-property relationships from a data science view.
Resistance to COVID-19 vaccination and the social contract: evidence from Italy
Authors: Kreps Sarah E. , Kriner Douglas L.
Published: April 2023

Confronted with stalled vaccination efforts against COVID-19, many governments embraced mandates and other measures to incentivize vaccination that excluded the unvaccinated from aspects of social and economic life. Even still, many citizens remained unvaccinated. We advance a social contract framework for understanding who remains unvaccinated and why. We leverage both observational and individual-level survey evidence from Italy to study the relationship between vaccination status and social context, social trust, political partisanship, and adherence to core institutional structures such as the rule of law and collective commitments. We find that attitudes toward the rule of law and collective commitments outside the domain of vaccination are strongly associated with compliance with vaccine mandates and incentives. Partisanship also corresponds with vaccine behaviors, as supporters of parties whose leaders criticized aggressive policies to incentivize or mandate vaccination and emphasized individual liberty are least likely to comply. Our findings suggest appeals emphasizing individual benefits may be more effective than appeals emphasizing collective responsibility.
Extracting Group Velocity Dispersion values using quantum-mimic Optical Coherence Tomography and Machine Learning
Authors: Maliszewski Krzysztof A. , Urbańska Magdalena A. , Kolenderski Piotr , Vetrova Varvara , Kolenderska Sylwia M.
Published: April 2023

Quantum-mimic Optical Coherence Tomography (Qm-OCT) images are cluttered with artefacts - parasitic peaks which emerge as a by-product of the algorithm used in this method. However, the shape and behaviour of an artefact are uniquely related to Group Velocity Dispersion (GVD) of the layer this artefact corresponds to and consequently, the GVD values can be inferred by carefully analysing them. Since for multi-layered objects the number of artefacts is too high to enable layer-specific analysis, we employ a solution based on Machine Learning. We train a neural network with Qm-OCT data as an input and dispersion profiles, i.e. depth distribution of GVD within an A-scan, as an output. By accounting for noise during training, we process experimental data and estimate the GVD values of BK7 and sapphire as well as provide a qualitative GVD value distribution in a grape and cucumber. Compared to other GVD-retrieving methods, our solution does not require user input, automatically provides dispersion values for all the visualised layers and is scalable. We analyse the factors affecting the accuracy of determining GVD: noise in the experimental data as well as general physical limitations of the detection of GVD-induced changes, and suggest possible solutions.
GATA6 coordinates cross-talk between BMP10 and oxidative stress axis in pulmonary arterial hypertension
Authors: Toyama Tetsuo , Kudryashova Tatiana V. , Ichihara Asako , Lenna Stefania , Looney Agnieszka , Shen Yuanjun , Jiang Lifeng , Teos Leyla , Avolio Theodore , Lin Derek , Kaplan Ulas , Marden Grace , Dambal Vrinda , Goncharov Dmitry , Delisser Horace , Lafyatis Robert , Seta Francesca , Goncharova Elena A. , Trojanowska Maria
Published: April 2023

Pulmonary arterial hypertension (PAH) is a life-threatening condition characterized by a progressive increase in pulmonary vascular resistance leading to right ventricular failure and often death. Here we report that deficiency of transcription factor GATA6 is a shared pathological feature of PA endothelial (PAEC) and smooth muscle cells (PASMC) in human PAH and experimental PH, which is responsible for maintenance of hyper-proliferative cellular phenotypes, pulmonary vascular remodeling and pulmonary hypertension. We further show that GATA6 acts as a transcription factor and direct positive regulator of anti-oxidant enzymes, and its deficiency in PAH/PH pulmonary vascular cells induces oxidative stress and mitochondrial dysfunction. We demonstrate that GATA6 is regulated by the BMP10/BMP receptors axis and its loss in PAECs and PASMC in PAH supports BMPR deficiency. In addition, we have established that GATA6-deficient PAEC, acting in a paracrine manner, increase proliferation and induce other pathological changes in PASMC, supporting the importance of GATA6 in pulmonary vascular cell communication. Treatment with dimethyl fumarate resolved oxidative stress and BMPR deficiency, reversed hemodynamic changes caused by endothelial Gata6 loss in mice, and inhibited proliferation and induced apoptosis in human PAH PASMC, strongly suggesting that targeting GATA6 deficiency may provide a therapeutic advance for patients with PAH.
Correlation between genotype and phenotype with special attention to hearing in 14 Japanese cases of NF2-related schwannomatosis
Authors: Oishi Naoki , Noguchi Masaru , Fujioka Masato , Nara Kiyomitsu , Wasano Koichiro , Mutai Hideki , Kawakita Rie , Tamura Ryota , Karatsu Kosuke , Morimoto Yukina , Toda Masahiro , Ozawa Hiroyuki , Matsunaga Tatsuo
Published: April 2023

NF2-related schwannomatosis (NF2) is an autosomal dominant genetic disorder caused by variants in the NF2 gene. Approximately 50% of NF2 patients inherit pathogenic variants, and the remainder acquire de novo variants. NF2 is characterized by development of bilateral vestibular schwannomas. The genetic background of Japanese NF2 cases has not been fully investigated, and the present report performed a genetic analysis of 14 Japanese NF2 cases and examined genotype–phenotype correlations. DNA samples collected from peripheral blood were analyzed by next-generation sequencing, multiplex ligation-dependent probe amplification analysis, and in vitro electrophoresis. Ten cases had pathogenic or likely pathogenic variants in the NF2 gene, with seven truncating variants and three non-truncating variants. The age of onset in all seven cases with truncating variants was < 20 years. The age of onset significantly differed among cases with truncating NF2 variants, non-truncating NF2 variants, and no NF2 variants. However, the clinical course of tumor growth and hearing deterioration were not predicted only by germline pathogenic NF2 variants. The rate of truncating variants was higher in the present study than that of previous reports. Genotype–phenotype correlations in the age of onset were present in the analyzed Japanese NF2 cases.