bluuebunny/crossref_metadata_2025 huggingface dataset:
Vacuolar H+-ATPase subunit a was identified as the target protein of the oomycete inhibitor fluopicolide
Authors: Dai Tan , Yang Jikun , Zhao Chuang , Zhang Can , Wang Zhiwen , Peng Qin , Liu Pengfei , Miao Jianqiang , Liu Xili
Published: April 2023

Approximately 240 fungicides are currently in use. However, only a few direct targets have been identified, which limits the development of fungicides and rapid resistance monitoring. Fluopicolide, which is an excellent oomycete inhibitor, is classified as delocalization of spectrin-like proteins inhibitors by FRAC. In the current study, aPcα-actininknockout had no effect on the sensitivity ofPhytophthora capsicito fluopicolide. The vacuolar H+-ATPase subunit a (PcVHA-a) was identified using a BSA-seq and DARTS assay. Four kinds of point mutations in PcVHA-a that cause fluopicolide resistance inP.capsiciwere confirmed using site-directed mutagenesis. The results of MST, molecular docking, and a DARTS assay indicated that PcVHA-a could bind fluopicolide. Sequence analysis and a molecular docking assay proved the specificity of fluopicolide to oomycetes or fish. Our results suggest that PcVHA-a is the target of fluopicolide, and H+-ATPase could be used as a novel target for the development of new fungicides.
Spatiotemporal transcriptome atlas of human embryos after gastrulation
Authors: Pan Jiexue , Li Yuejiao , Lin Zhongliang , Lan Qing , Chen Huixi , Zhai Man , Sui Shengwei , Zhang Gaochen , Cheng Yi , Tang Yunhui , Wang Qingchen , Zhang Ying , Ma Fuhe , Xu Yue , Mao Yiting , Chen Qinfang , Guan Yichun , Meng Nan , Lu Haiqian , Li Xiangjuan , Zheng Tingting , Yao Xiaoying , Qin Qiuyu , Jiang Bin , Ren Yuxing , Luo Meiqi , Nancuo Ji , Jin Xin , Sheng Jianzhong , Xu Congjian , Liu Xinmei , Wu Yanting , Xu Chenming , Zhao Lijian , Yang Hongbo , Gao Ya , Ding Guolian , Xu Xun , Huang Hefeng
Published: April 2023

The spatial and temporal atlas of gene expression in the human embryo at early gestation is critical in understanding embryo development, organogenesis, and disease origins. We obtained the spatiotemporal transcriptome from 90 sagittal sections of 16 whole human embryos from 3 to 8 post-conception weeks by Stereo-seq with high resolution and ultra-large field, establishing the development trajectory/regulatory profiling of 49 organs. We uncovered the organ-specific regulons as potential lineage-determining factors and identified the new regulatory networks during heart and brain development. The atlas refines the key organs/cell types vulnerable to virus infection and genetic disorders, and, reveals the dynamics of allelic gene expression in specific organs at different stages. These results present the first comprehensive delineation of the spatiotemporal transcriptomic dynamics of human organogenesis.

One Sentence Summary

The spatiotemporal transcriptome atlas presents a comprehensive delineation of human embryogenesis after gastrulation.
Factorized visual representations in the primate visual system and deep neural networks
Authors: Lindsey Jack W. , Issa Elias B.
Published: April 2023

Object classification has been proposed as a principal objective of the primate ventral visual stream and has been used as an optimization target for deep neural network models (DNNs) of the visual system. However, visual brain areas represent many different types of information, and optimizing for classification of object identity alone does not constrain how other information may be encoded in visual representations. Information about different scene parameters may be discarded altogether (“invariance”), represented in non-interfering subspaces of population activity (“factorization”) or encoded in an entangled fashion. In this work, we provide evidence that factorization is a normative principle of biological visual representations. In the monkey ventral visual hierarchy, we found that factorization of object pose and background information from object identity increased in higher-level regions and strongly contributed to improving object identity decoding performance. We then conducted a large-scale analysis of factorization of individual scene parameters – lighting, background, camera viewpoint, and object pose – in a diverse library of DNN models of the visual system. Models which best matched neural, fMRI and behavioral data from both monkeys and humans across 12 datasets tended to be those which factorized scene parameters most strongly. Notably, invariance to these parameters was not as consistently associated with matches to neural and behavioral data, suggesting that maintaining non-class information in factorized activity subspaces is often preferred to dropping it altogether. Thus, we propose that factorization of visual scene information is a widely used strategy in brains and DNN models thereof.
Interactions between fitness components across the life cycle constrain competitor coexistence
Authors: Gómez‐Llano Miguel , Boys Wade A. , Ping Taylor , Tye Simon P. , Siepielski Adam M.
Published: April 2023

Numerous mechanisms can promote competitor coexistence. Yet, these mechanisms are often considered in isolation from one another. Consequently, whether multiple mechanisms shaping coexistence combine to promote or constrain species coexistence remains an open question.

Here, we aim to understand how multiple mechanisms interact within and between life stages to determine frequency‐dependent population growth, which has a key role stabilizing local competitor coexistence.

We conducted field experiments in three lakes manipulating relative frequencies of two Enallagma damselfly species to evaluate demographic contributions of three mechanisms affecting different fitness components across the life cycle: the effect of resource competition on individual growth rate, predation shaping mortality rates, and mating harassment determining fecundity. We then used a demographic model that incorporates carry‐over effects between life stages to decompose the relative effect of each fitness component generating frequency‐dependent population growth.

This decomposition showed that fitness components combined to increase population growth rates for one species when rare, but they combined to decrease population growth rates for the other species when rare, leading to predicted exclusion in most lakes.

Because interactions between fitness components within and between life stages vary among populations, these results show that local coexistence is population specific. Moreover, we show that multiple mechanisms do not necessarily increase competitor coexistence, as they can also combine to yield exclusion. Identifying coexistence mechanisms in other systems will require greater focus on determining contributions of different fitness components across the life cycle shaping competitor coexistence in a way that captures the potential for population‐level variation.
Manhood, Military Forts and Ethnological Thought: John Gregory Bourke and the Rise of Border Ethnology, 1870s–90s
Authors: Hernández Kris Klein
Published: April 2023

This article explores how some army forts in 1870s, 1880s and 1890s Texas, New Mexico and Arizona emerged as sites for the production of ethnological knowledge about Mexican and native (Apache, Zuni) peoples. It focuses primarily on US Army Captain John Gregory Bourke's diary entries and publications about his time in Texas, New Mexico and Arizona military garrisons from the late 1860s to the 1890s. Expanding upon cultural studies scholar José Limón's discussions of Bourke's ambivalent relationship to the subjects of his ethnographic study, this article investigates how Bourke's excursions into the built‐environment in and beyond border military forts shaped his understanding of the logics of empire and how his writing, in turn, influenced popular conceptions of the borderlands. Turning to historian Gail Bederman's exploration of turn‐of‐the‐century conceptions of manhood, this article examines how Bourke's ethnographic forays from the homosocial and white‐dominated enclosure of the military fort into the multi‐racial and gendered borderlands defined and challenged ideas about manhood and masculinity on the ‘frontier’. This article proposes that the study of army fort personnel helps tease out how militarised individuals made sense of the built‐environment through their racial and gendered observations of border populations.
Emergency short stay area improves access and flow in a rural hospital
Authors: Smith Anne B , Davis Kimberley J
Published: April 2023

Objectives

Shoalhaven District Memorial Hospital is a rural (MM3) 150‐bed hospital in Nowra, New South Wales, whose ED has evolved to a FACEM‐led model of care (MOC). It has never had an emergency short stay area (ESSA). The objective of the present study was to pilot an ESSA and determine whether this MOC would increase the operational performance of the ED.

Methods

An ESSA was designed and delivered by emergency medicine medical, nursing and allied health practitioners. The study period was July–December 2021, with a seasonally matched retrospective cohort of records extracted for comparison (July–December 2020). Both took place within the context of the ongoing COVID‐19 pandemic. The primary outcome measured was percentage of admitted patients meeting Emergency Treatment Performance (ETP). Secondary outcomes included discharge ETP, overall ED and inpatient length of stay (LOS), mortality and representation rates.

Results

The admission ETP for patients after the implementation of the ESSA significantly increased, from 13.9% to 31.6% (χ2 = 288, P < 0.001). Discharge ETP significantly declined. There was no effect improvement on overall ETP. There was no change to mortality or representation rates. Average admission LOS decreased.

Conclusions

The introduction of the ESSA significantly improved the ETP of admitted patients. Ongoing refinement of the ESSA admission processes, as well as the lifting of certain COVID‐19 restrictions, could show even greater improvements in this and other areas. Ongoing research in this field is necessary, as well as a more detailed cost–benefit analysis.
iPhenology: Using open‐access citizen science photos to track phenology at continental scale
Authors: Klinger Yves P. , Eckstein R. Lutz , Kleinebecker Till
Published: April 2023

Photo observations are a highly valuable but rarely used source of citizen science (CS) data. Recently, the number of publicly available photo observations has increased strongly, for example, due to the use of smartphone applications for species identification. This has enabled the raising of ecological insights in poorly studied subjects. One of the fields with the highest potential to benefit from the use of photo observations is phenology.

We propose a workflow for iPhenology, the use of publicly available photo observations to track phenological events at large scales. The workflow comprises data acquisition, cleaning of observations, phenological classification and modelling spatiotemporal patterns of phenology. We explore the suitability of iPhenology to observe key phenological stages in the plant reproductive cycle of a model species and discuss limitations and future prospects of the approach using the example of an invasive species in Europe.

We show that iPhenology is suitable to track key phenological events of widespread species. However, the number and quality of available observations may differ among species and phenological stages.

Overall, publicly available CS photo observations are suitable to track key phenological events and can thus significantly advance the knowledge on the timing and drivers of plant phenology. In future, integrating the workflow with automated image processing and analysis may enable real‐time tracking of plant phenology.
An update on recent developments and highlights in food allergy
Authors: Locke Arielle , Hung Lisa , Upton Julia E. M. , O'Mahony Liam , Hoang Jennifer , Eiwegger Thomas
Published: April 2023

While both the incidence and general awareness of food allergies is increasing, the variety and clinical availability of therapeutics remain limited. Therefore, investigations into the potential factors contributing to the development of food allergy (FA) and the mechanisms of natural tolerance or induced desensitization are required. In addition, a detailed understanding of the pathophysiology of food allergies is needed to generate compelling, enduring, and safe treatment options. New findings regarding the contribution of barrier function, the effect of emollient interventions, mechanisms of allergen recognition, and the contributions of specific immune cell subsets through rodent models and human clinical studies provide novel insights. With the first approved treatment for peanut allergy, the clinical management of FA is evolving toward less intensive, alternative approaches involving fixed doses, lower maintenance dose targets, coadministration of biologicals, adjuvants, and tolerance‐inducing formulations. The ultimate goal is to improve immunotherapy and develop precision‐based medicine via risk phenotyping allowing optimal treatment for each food‐allergic patient.
The association between uterine adenomyosis and adverse obstetric outcomes: A propensity score‐matched analysis
Authors: Mandelbaum Rachel S. , Melville Samuel J. F. , Violette Caroline J. , Guner Joie Z. , Doody Kaitlin A. , Matsuzaki Shinya , Quinn Molly M. , Ouzounian Joseph G. , Paulson Richard J. , Matsuo Koji
Published: April 2023

Introduction

This study examined obstetric outcomes in patients diagnosed with uterine adenomyosis.

Material and methods

This historical cohort study queried the Healthcare Cost and Utilization Project's National Inpatient Sample. The study population was all hospital deliveries in women aged 15–54 years between January 2016 and December 2019. The exposure was a diagnosis of uterine adenomyosis. The main outcome measures were obstetric characteristics, including placenta previa, placenta accreta spectrum, and placental abruption. Secondary outcomes were delivery complications including severe maternal morbidity. Analytic steps to assess these outcomes included (i) a 1‐to‐N propensity score matching to mitigate and balance prepregnancy confounders to assess obstetric characteristics, followed by (ii) an adjusting model with preselected pregnancy and delivery factors to assess maternal morbidity. Sensitivity analyses were also performed with restricted cohorts to account for prior uterine scar, uterine myoma, and extra‐uterine endometriosis.

Results

After propensity score matching, 5430 patients with adenomyosis were compared to 21 720 patients without adenomyosis. Adenomyosis was associated with an increased odds of placenta accreta spectrum (adjusted‐odds ratio [aOR] 3.07, 95% confidence interval [CI] 2.01–4.70), placenta abruption (aOR 3.21, 95% CI: 2.60–3.98), and placenta previa (aOR 5.08, 95% CI: 4.25–6.06). Delivery at <32 weeks of gestation (aOR 1.48, 95% CI: 1.24–1.77) and cesarean delivery (aOR 7.72, 95% CI: 7.04–8.47) were both increased in women with adenomyosis. Patients in the adenomyosis group were more likely to experience severe maternal morbidity at delivery compared to those in the nonadenomyosis group (aOR 1.86, 95% CI: 1.59–2.16). Results remained robust in the aforementioned several sensitivity analyses.

Conclusions

This national‐level analysis suggests that a diagnosis of uterine adenomyosis is associated with an increased risk of placental pathology (placenta accreta spectrum, placenta abruption, and placental previa) and adverse maternal outcomes at delivery.
Homeless youth‐led activism and direct action: Lessons from a participatory research project in Tio'tia:ke/Montréal
Authors: Malenfant Jayne , Watchorn Mickey , Nichols Naomi
Published: April 2023

This article explores the involvement of youth with lived experience (LE) in activism and research aimed at addressing youth homelessness in Canada. Based within a youth‐participatory action research project in Tio'tiá:ke/Montréal, Canada, we reflect on how young people described their own activist organising, as well as the practical ways we may harness actions that homelessness youth are already doing to create communities and solidarity. The authors are members of Youth Action Research Revolution (YARR), a research team primarily made up of youth with LE of homelessness. We position the analysis at an intersection of our own experiences and 63 interviews with youth aged 16–29 conducted by YARR from 2018 to 2021. Conceiving of participatory, youth‐led research as a form of direct action we outline lessons learned from our own research and LE. Young people within our team and participants in YARR's research shared critiques of State systems while outlining the work that they undertook with their peers to act on issues of housing precarity, often eschewing activism aimed at State processes or institutional reform in favour of direct action. This article proposes a mode of fostering youth‐led, socially just change around homelessness—one that shifts conversations from inclusion to solidarity, and recognises the radical potential of research by‐and‐for young people. The authors conclude that research and advocacy on homelessness is always inherently political for young people with LE, and that harnessing the direct action that youth already do to survive is not only a socially just form of mobilising, but can contribute to broader activism towards housing justice.
Does the early childhood education and care in India contribute to children's skill development?
Authors: Ghosh Saikat
Published: April 2023

Early childhood education and care (ECEC) is a crucial intervention because of its long‐term impact on child development. However, information concerning the effectiveness of the ECEC in developing countries like India is sparsely available. This empirical study drew upon primary data collected from India's eastern state, West Bengal and investigated whether attending preschool contributed to children's cognitive and social skill development. The study found that attending preschool did not provide dividends in the form of cognitive and social skill accumulation. Furthermore, attending private preschool was associated with socioemotional development but no cognitive development. Moreover, parents' education seems to be a strong predictor for child's development. Given the findings of this paper, preschools in India, both in the public and private sectors, would need considerable quality improvement to deliver developmentally appropriate ECEC to children. It is particularly relevant in the context of the new National Education Policy in India, which emphasises the need to provide universal access to high‐quality ECCE to all young children across the country.
Relationship between lower urinary tract symptoms and frailty
Authors: Ozaki Yusuke , Hatakeyama Shingo , Imai Atsushi , Songee Jung , Soma Osamu , Ozaki Kai , Fujita Naoki , Okamoto Teppei , Iwamura Hiromichi , Yamamoto Hayato , Yoneyama Takahiro , Hashimoto Yasuhiro , Ohyama Chikara
Published: April 2023

Objective

To elucidate the relationship between frailty and lower urinary tract symptoms (LUTS).

Methods

We longitudinally evaluated the temporal changes and the relationships between frailty and LUTS in 247 community‐dwelling adults (45 years or older) at baseline and at a 5‐year follow‐up. We used the Fried phenotype (phenotype‐based frailty), 5‐item modified frailty index (5i‐mFI; comorbidity‐based frailty), and frailty discriminant score (comprehensive frailty assessment) to evaluate frailty. LUTS were evaluated using the international prostate symptom score (IPSS) and overactive bladder symptom score (OABSS).

Results

We analyzed 247 participants with a median age of 60 years. The median IPSS and OABSS were significantly increased over the 5 years. The proportion of frail individuals did not increase significantly over the 5 years. Of the three frailty assessment tools, the 5i‐mFI score significantly increased between 2014 and 2019. Multiple linear regression analyses showed that the 5i‐mFI score was significantly associated with the severity of LUTS in 2014 to 5i‐mFI in 2019 but not with 5i‐mFI in 2014 to the severity of LUTS in 2019.

Conclusion

The effect of LUTS on frailty might be greater than the effect of frailty on LUTS. Further large‐scale studies are needed to elucidate the relationship between LUTS and frailty.
Field strength effect on elastoplastic behavior of aluminoborosilicate glass: I. Elastic moduli and indentation size effect
Authors: Fry Aubrey L. , Ogrinc Andrew L. , Kim Seong H. , Mauro John C.
Published: April 2023

The modifier field strength (FS) is believed to play an important role in determining the elastic–plastic responses of aluminoborosilicate (ABS) glasses, but its effect is not well understood. Three novel alkali and three alkaline earth (AE) ABS compositions were created for this study which is the first part of two studies that explored the elastoplastic responses of these glasses. Six compositions were designed using different network modifiers (NWMs) to cover a range of cation FS. The glasses were also designed such that the concentrations of NWM and Al2O3 were similar, which maximized the three‐coordinated boron fraction in the network. It is well known that modifier FS can affect the coordination number (CN) of Al and B in an ABS glass structure, for example, a higher FS modifier can promote B3 → B4 and higher [Al5,6], but the degree of this depends on network former (NWF) ratios. Previous work used solid‐state NMR spectroscopic analysis on the current glasses to find that there was variation between [B4] and [Al4] between the two glass series (alkali vs. AE) but that was attributed to synthesis factors and no trend with FS was associated with the varying NWF CN. Further, 29Si ssNMR showed no evidence of NBOs which made sense based on composition. The conclusion, therefore, was that there was a far greater correlation with modifier FS for the increased mechanical and physical properties rather than the CN of Al and B. Part I of the current work focused on the elastic moduli, Poisson's ratio, the indentation size effect (ISE), and the bow‐in parameter. This part laid out the foundation to investigate the intersection of these elastoplastic properties with hardness and crack resistance as a function of NWM FS. Results showed that: (i) the Young's, bulk, and shear moduli increased with modifier FS, whereas Poisson's ratio did not trend with FS; (ii) the alkali glasses had a significantly higher magnitudes of ISE compared to the AE glasses; and (iii) the bow‐in parameter was load dependent and decreased with modifier FS at the highest indentation load.
Microelectrode voltage mapping for substrate assessment in catheter ablation of ventricular tachycardia: A dual‐center experience
Authors: Dello Russo Antonio , Compagnucci Paolo , Bergonti Marco , Cipolletta Laura , Parisi Quintino , Volpato Giovanni , Santarelli Giulia , Colonnelli Michela , Saenen Johan , Valeri Yari , Carboni Laura , Marchese Procolo , Marini Marco , Sarkozy Andrea , Natale Andrea , Casella Michela
Published: April 2023

Introduction

The assessment of the ventricular myocardial substrate critically depends on the size of mapping electrodes, their orientation with respect to wavefront propagation, and interelectrode distance. We conducted a dual‐center study to evaluate the impact of microelectrode mapping in patients undergoing catheter ablation (CA) of ventricular tachycardia (VT).

Methods

We included 21 consecutive patients (median age, 68 [12], 95% male) with structural heart disease undergoing CA for electrical storm (n = 14) or recurrent VT (n = 7) using the QDOT Micro catheter and a multipolar catheter (PentaRay, n = 9). The associations of peak‐to‐peak maximum standard bipolar (BVc) and minibipolar (PentaRay, BVp) with microbipolar (BVμMax) voltages were respectively tested in sinus rhythm with mixed effect models. Furthermore, we compared the features of standard bipolar (BE) and microbipolar (μBE) electrograms in sinus rhythm at sites of termination with radiofrequency energy.

Results

BVμMax was moderately associated with both BVc (β = .85, p < .01) and BVp (β = .56, p < .01). BVμMax was 0.98 (95% CI: 0.93−1.04, p < .01) mV larger than corresponding BVc, and 0.27 (95% CI: 0.16−0.37, p < .01) mV larger than matching BVp in sinus rhythm, with higher percentage differences in low voltage regions, leading to smaller endocardial dense scar (2.3 [2.7] vs. 12.1 [17] cm2, p < .01) and border zone (3.2 [7.4] vs. 4.8 [20.1] cm2, p = .03) regions in microbipolar maps compared to standard bipolar maps. Late potentials areas were nonsignificantly greater in microelectrode maps, compared to standard electrode maps. At sites of VT termination (n = 14), μBE were of higher amplitude (0.9 [0.8] vs. 0.4 [0.2] mV, p < .01), longer duration (117 [66] vs. 74 [38] ms, p < .01), and with greater number of peaks (4 [2] vs. 2 [1], p < .01) in sinus rhythm compared to BE.

Conclusion

microelectrode mapping is more sensitive than standard bipolar mapping in the identification of viable myocytes in SR, and may facilitate recognition of targets for CA.
Emotion‐focused skills training for parents with anxious children. A pilot study
Authors: Zahl‐Olsen Rune , Severinsen Linda , Shahar Ben , Stiegler Jan Reidar , Bertelsen Thomas Bjerregaard
Published: April 2023

Anxiety disorders are common among children and adolescents. Effective treatments exist, but meta‐analyses indicate that 40% of children continue to have significant symptoms posttreatment. Alternative therapeutic interventions are needed. Emotion‐focused parental interventions have been found to be effective in targeting children's internalizing difficulties, but no research has examined remission. In this pilot trial, we examined whether Emotion Focused Skills Training (EFST) was associated with remission of diagnosis in children with anxiety. Nine 8–14‐year‐olds diagnosed with anxiety were recruited at a mental health clinic in Norway. Both parents of each child attended a 2‐day EFST program followed by five 1‐hour weekly sessions. Pre‐ and posttreatment diagnosis and severity were evaluated using a multiinformant approach using the Spence Children's Anxiety Scale and the Anxiety Disorders Interview Schedule. After treatment, 33% no longer met criteria for any anxiety diagnosis, 66% obtained remission from their primary anxiety diagnosis, and 89% from at least one.
Automated rapid response system activation—Impact on nurses' attitudes and perceptions towards recognising and responding to clinical deterioration: Mixed‐methods study
Authors: Chua Wei Ling , Wee Li‐Phing Clarice , Lim Jia Ying Germaine , Yeo Min Li Kimberly , Jones Daryl , Tan Chee Keat , Khan Faheem Ahmed , Liaw Sok Ying
Published: April 2023

Aim

To explore general ward nurses' attitudes and perceptions towards recognising and responding to clinical deterioration in a hospital with automated rapid response system activation.

Background

There is growing interest in deploying automated clinical deterioration notification systems to reduce delayed or failed recognition and response to clinical deterioration of ward patients. However, little is known about its impact on ward nurses' perspectives and work patterns.

Design

A mixed‐methods study.

Methods

Online survey of 168 registered nurses and individual interviews with 10 registered nurses in one acute hospital in Singapore. The study adhered to the STROBE checklist for cross‐sectional studies and the COREQ guidelines for qualitative studies.

Results

Many nurses (38.1%) rarely performed patient assessments or observations other than vital signs assessment to assess for early signs of clinical deterioration. About 30% were worried about being criticised for calling the primary team doctors. Four themes emerged from the qualitative analysis: automated rapid response system activation as a safety net, being more cautious with vital signs monitoring, the NEWS2 alone is inadequate, and ward nurses as the ‘middleman’ between the intensive care unit outreach nurse and primary team doctors.

Conclusions

Although nurses value the automated rapid response system activation as a safety net to minimise delays in accessing urgent critical care resources, it does not address the sociocultural barriers inherent in escalation of care. Although the automated system led nurses to be more cautious with vital signs monitoring, it does not encourage them to perform comprehensive patient assessments to detect early signs of deterioration.

Relevance to clinical practice

Nurse education on assessing for clinical deterioration should focus on the use of broader patient assessment skills other than vital signs. Sociocultural barriers to escalation of care remain a key issue that needs to be addressed by hospital management.

No patient or public contribution

No patients, service users, care‐givers or members of the public were involved in the study.
Antisuit injunctions in SEP disputes and the recent EU's WTO/TRIPS case against China
Authors: Bonadio Enrico , Lucchi Nicola
Published: April 2023

The existence of standard essential patents (SEPs)—and the associated litigation—has potentially disruptive consequences for the manufacture, marketing and distribution of complex products that incorporate many patented standards, for example, information and communication technology (ICT) products such as smartphones that incorporate a camera, video, web browser, wireless communications, text messaging, and so on, as well as an increasing number of ‘connected’ Internet of Things products such as wearable devices and ‘smart home’ devices. Indeed, SEP owners may use the patent enforcement system to prevent implementers of these technologies from bringing to market competing products that use the same standards. As is known, this raises concerns about competition in the market and the need to maintain interoperability to ensure the development of the ICT industry. One of the legal tools which can be used by implementers to (try to) neutralise SEP holders' anticompetitive behaviours is the ‘antisuit injunction’ (ASI). ASIs are not uncommon in common law jurisdictions while they are foreign to civil law countries within the European Union (EU). ASIs are particularly useful to SEP implementers when patent holders disrespect their commitment to license their patents on a FRAND basis. For example, a judge who is in the process of assessing whether the SEP owner complies with FRAND terms may at the same time grant an ASI to stop the patentee taking patent infringement actions in other jurisdictions until the FRAND litigation has been concluded. In February 2022, the EU filed a complaint at the World Trade Organization (WTO), arguing that China's use of ASIs prevents EU‐based companies from properly protecting their SEPs. Indeed, ASIs have recently been granted in several Chinese disputes, including in Huawei v Conversant and Xiaomi v. InterDigital. More specifically, China's Supreme People's Court held that Chinese courts can use ASIs to prevent SEP owners from filing disputes in any foreign courts to enforce their patents; and that anyone who does not comply with the injunction should be fined €130,000 per day. In the WTO case the EU notes that such a case law jeopardises innovation and growth in Europe, ‘effectively depriving European technology companies of the possibility to exercise and enforce the rights that give them a technological edge’. From a legal perspective, according to the EU, China's conduct is in violation of various Trade‐Related Aspects of Intellectual Property Rights (TRIPS) provisions, including Article 28 which grants exclusive rights to patent owners. The paper focuses on this EU–China WTO/TRIPS dispute and more generally, on the relevance of ASIs within SEP cases.
Analysis of seismically‐isolated two‐block systems using a multi–rocking‐body dynamic model
Authors: Destro Bisol Giacomo , DeJong Matthew , Liberatore Domenico , Sorrentino Luigi
Published: April 2023

A novel multibody rocking model is developed to investigate the dynamic response of two stacked rigid blocks placed on a linear base isolation device. The model is used to investigate the dynamic response of a realistic statue‐pedestal system subject to pulse‐like ground motions. The analysis shows that, in general, base isolation increases the safety level of the rocking system. However, for large period pulses or small size blocks, the isolator can amplify the ground motion, resulting in a lower minimum overturning acceleration than for the nonisolated system. Further, the amplification or shock spectrum of a linear mass‐dashpot‐spring oscillator, was found to be the reciprocal of the minimum nondimensional overturning acceleration of the investigated rocking system. Novel rocking spectra are obtained by normalizing the frequency of the pulse by the frequency of the isolator. The analysis also demonstrates how the dynamic response of the two stacked blocks is equivalent to that of a single‐block configuration coincident with the whole system assumed monolithic or the upper block alone, whichever is more slender.
A retrospective case–control study of gastrostomy use in children undergoing hematopoietic cell transplantation
Authors: Mellgren Karin , Nicolajsen Tom , Christoforaki Tania Panagiota , Juan Sara Marin , Mårtensson Thomas , Toporski Jacek , Casswall Thomas H. , Gustafsson Britt
Published: April 2023

Background

Maintaining a good nutritional status during the hematopoietic cell transplantation (HCT) procedure is challenging in the pediatric population.

Methods

In a multicentric retrospective study, we compared the outcome of nutritional status and HCT‐related parameters in 227 pediatric patients during and after HCT between 2005 and 2015. 112 patients received a gastrostomy before the start of HCT (GS group), and 115 did not receive a gastrostomy (NGS). Data collection was performed at HCT, 3, 6, and 12 months post‐HCT.

Results

At time point of HCT the Standard Deviation Score (SDS) of weight was 0.17 in the NGS group, and 0.71 in the GS group (p = .01) Patients in the NGS group lost more weight during the first 3 months after HCT than patients in the GS group. At 12 months, patients in the NGS remained at a lower weight, while patients in the GS group slightly increased their weight.

There were no differences between the groups in the incidence of acute graft‐versus‐host‐disease (GvHD), overall survival, and non‐relapse mortality. However, the number of febrile episodes requiring intravenous treatment with antibiotics, was higher in the GS group as compared to the NGS group, during the first 3 months post‐HCT (p < .001).

Conclusions

Our results indicate that gastrostomy can be utilized in children undergoing HCT without any negative effects on mortality. Therefore, the use of a gastrostomy appears to be a safe option to maintain a good nutritional status during the HCT procedure.
Comprehensive analysis of physiological and metabolomic responses to drought reveals specific modulation of acquired tolerance mechanisms in rice
Authors: Doddaraju Pushpa , Dharmappa Prathibha M. , Thiagarayaselvam Aarthy , Vijayaraghavareddy Preethi , Bheemanahalli Raju , Basavaraddi Priyanka A. , Malagondanahalli Mohan Kumar V. , Kambalimath Sumanth , Thulasiram Hirekodathakallu V. , Sreeman Sheshshayee M.
Published: April 2023

Mild stresses induce “acquired tolerance traits” (ATTs) that provide tolerance when stress becomes severe. Here, we identified the genetic variability in ATTs among a panel of rice germplasm accessions and demonstrated their relevance in protecting growth and productivity under water‐limited conditions. Diverse approaches, including physiological screens, association mapping and metabolomics, were adopted and revealed 43 significant marker‐trait associations. Nontargeted metabolomic profiling of contrasting genotypes revealed 26 “tolerance‐related‐induced” primary and secondary metabolites in the tolerant genotypes (AC‐39000 and AC‐39020) compared to the susceptible one (BPT‐5204) under water‐limited condition. Metabolites that help maintain cellular functions, especially Calvin cycle processes, significantly accumulated more in tolerant genotypes, which resulted in superior photosynthetic capacity and hence water use efficiency. Upregulation of the glutathione cycle intermediates explains the ROS homeostasis among the tolerant genotypes, maintaining spikelet fertility, and grain yield under stress. Bioinformatic dissection of a major effect quantitative trait locus on chromosome 8 revealed genes controlling metabolic pathways leading to the production of osmolites and antioxidants, such as GABA and raffinose. The study also led to the identification of specific trait donor genotypes that can be effectively used in translational crop improvement activities.
Metabolomic exhibits different profiles and potential biomarkers of Vitis spp. co‐cultivated with Fusarium oxysporum for short, medium, and long times
Authors: Costa Igor Rafael Sousa , Cavalcante Francisco Lucas Pacheco , Cavalcanti Fábio Rossi , de Freitas Fernandes Cleberson , Gomes‐Filho Enéas , Canuto Kirley Marques , de Carvalho Humberto Henrique
Published: April 2023

Differential rootstock tolerance to Fusarium spp. supports viticulture worldwide. However, how plants stand against the fungus still needs to be explored. We hypothesize it involves a differential metabolite modulation. Thus, we performed a gas chromatography coupled with mass spectrometry (GC–MS) analysis of Paulsen P1103 and BDMG573 rootstocks, co‐cultured with Fusarium oxysporum (FUS) for short, medium, and long time (0, 4, and 8 days after treatment [DAT]). In shoots, principal component analysis (PCA) showed a complete overlap between BDMG573 non‐co‐cultivated and FUS at 0 DAT, and P1103 treatments showed a slight overlap at both 4 and 8 DAT. In roots, PCA exhibited overlapping between BDMG573 treatments at 0 DAT, while P1103 treatments showed overlapping at 0 and 4 DAT. Further, there is a complete overlapping between BDMG573 and P1103 FUS profiles at 8 DAT. In shoots, 1,3‐dihydroxyacetone at 0 and 4 DAT and maltose at 4 and 8 DAT were biomarkers for BDMG573. For P1103, glyceric acid, proline, and sorbitol stood out at 0, 4, and 8 DAT, respectively. In BDMG573 roots, the biomarkers were β‐alanine at 0 DAT, cellobiose and sorbitol at both 4 and 8 DAT. While in P1103 roots, they were galactose at 0 and 4 DAT and 1,3‐dihydroxyacetone at 8 DAT. Overall, there is an increase in amino acids, glycolysis, and tricarboxylic acid components in tolerant Paulsen P1103 shoots. Thus, it provides a new perspective on the primary metabolism of grapevine rootstocks to F. oxysporum that may contribute to strategies for genotype tolerance and early disease identification.
Virus‐infected mast cells activate virus‐specific CD8+ T cells
Authors: Hackler Yana , Siebenhaar Frank , Maurer Marcus , Muñoz Melba
Published: April 2023

Efficient anti‐viral responses of CD8+ T cells require signals that promote their effector cell differentiation, that are mainly provided by dendritic cells (DCs). Mast cells (MCs) are key drivers of DC maturation, but also influence their migration and antigen presenting properties and therefore indirectly mediate CD8+ T cell activation. MCs initiate innate immune responses at pathogen entry sites, promote the development of adaptive immune responses after infection, and release mediators including chemokines that recruit and activate immune cells including T cells during viral infections. However, whether MCs can directly activate virus‐specific CD8+ T cells remains largely unknown. Here, we used an in vitro viral infection model with lymphocytic choriomeningitis virus (LCMV)‐infected MCs or DCs co‐cultured with either LCMV‐specific CD8+ T cells or with WT (unspecific) CD8+ T cells. Similar to LCMV‐infected DCs, LCMV‐infected MCs clustered with virus‐specific CD8+ T cells and induced their activation and production of antiviral cytokines. In addition, the co‐stimulatory molecules CD86 and OX40L, but not CD80, were upregulated on MCs and an increased production of IL‐6 and type I interferons after LCMV infection was shown. Our findings suggest that MCs can promote CD8+ T cell activation during viral infections. MC‐mediated CD8+ T cell activation might be especially important within infected tissues where direct cellular interaction can take place. A better understanding of anti‐viral functions of MCs may help developing new strategies to better treat viral infections.
Evaluating the clinical utility of the systemic inflammatory response syndrome criteria in dogs and cats presenting to an emergency department
Authors: Spillane Amanda M. , Haraschak Jenica L. , Gephard Savanna E. , Nerderman Brooke E. , Fick Meghan E. , Reinhart Jennifer M.
Published: April 2023

Objective

Evaluate the clinical utility of the systemic inflammatory response syndrome (SIRS) criteria in dogs and cats presenting to an emergency room (ER).

Design

Prospective and retrospective observational study, conducted from November 2019 to February 2020.

Setting

Small animal university teaching hospital.

Animals

Prospective enrollment of 1143 dogs and 384 cats consecutively presenting to the ER. Retrospective enrollment of 65 healthy dogs and 57 healthy cats consecutively presenting to the primary care (PC) service.

Interventions

None.

Measurements and Main Results

Positive SIRS‐3 status was defined as meeting ≥2 of 3 (dogs) or 3 of 3 (cats) of the vital parameter SIRS criteria (temperature, heart rate, and respiratory rate). Positive SIRS‐4 status was defined as meeting ≥2 of 4 (dogs) and ≥3 of 4 (cats) of the vital parameter and CBC SIRS criteria. For each species, proportions of SIRS‐positive animals were compared between the ER and PC groups. Clinical outcomes were compared between SIRS‐positive and SIRS‐negative patients presenting to ER. The number of SIRS‐3‐positive dogs was statistically but not clinically different between the ER (69.9%) and PC (53.8%) groups (P = 0.009). Overall survival rate was 83% for SIRS‐3‐positive and 89% for SIRS‐3‐negative dogs presented to ER (P = 0.007). The number of SIRS‐3‐positive cats did not differ between ER and PC groups (P > 0.999). Overall survival rate was 61.1% for SIRS‐4‐positive and 86.8% for SIRS‐4‐negative cats presented to ER (P = 0.012).

Conclusions

Fulfilling the SIRS criteria is common in dogs and rare in cats regardless of presenting service. Meeting SIRS criteria on ER presentation carries a weak negative survival association in dogs and a moderate negative survival association in cats. This study demonstrates that the SIRS criteria have poor discriminatory ability to differentiate healthy from diseased patients and lacks a strong outcome correlation in small animal patients.
Tartaric acid induces toxicity in Madin–Darby canine kidney cells, but not human kidney‐2 cells in vitro, and is prevented by organic anion transporter inhibition and human OAT‐4 transfection
Authors: Coyne Sean R. , Landry Greg M.
Published: April 2023

Objectives

To evaluate the effect of tartaric acid (TTA) on Madin–Darby canine kidney (MDCK) cells compared to human kidney (HK)‐2 cells. Secondarily, to evaluate the effects of probenecid, an organic anion transporter (OAT)‐1 inhibitor, as well as human (h)OAT‐4 transfection into MDCK cells to prevent TTA‐induced cytotoxicity through decreasing accumulation via OAT‐1 uptake inhibition or increasing OAT‐4‐mediated TTA efflux.

Design

Seventy‐two‐hour TTA concentration response and inhibitor studies in immortalized cell lines.

Setting

School of Pharmacy biomedical research laboratory and tissue culture facility.

Animals/Samples

MDCK and HK‐2 immortalized cell lines.

Interventions

Both cell lines were treated with increasing concentrations of TTA for 72 hours. Additionally, MDCK cells were co‐incubated with TTA and increasing concentrations of probenecid or had been transfected with hOAT‐4 and subsequently treated with TTA for 72 hours.

Measurements and Main Results

Media and samples were collected and lactate dehydrogenase (LDH) release was measured. LDH release was measured to assess TTA‐induced cytotoxicity after 72 hours. LDH was not significantly increased in the HK‐2 cells at any concentration but was significantly increased in the MDCK cells from 10 to 100 mM. LDH concentrations were significantly decreased (61%) in MDCK cells incubated with 50 mM TTA and probenecid when compared to TTA alone. hOAT‐4 MDCK cell transfection also significantly reduced LDH release (57%) when comparing the transfected MDCK cells to the nontransfected MDCK cells treated with 50 mM TTA.

Conclusions

TTA is a species‐specific nephrotoxicant in dogs due to an interspecies difference in OAT‐4 expression. Inhibiting TTA uptake in MDCK cells in vitro using the OAT‐specific inhibitor, probenecid, prevents TTA‐induced cytotoxicity.
ACVECC‐Veterinary Committee on Trauma registry report 2017–2019
Authors: Hall Kelly E. , Rutten Jessica I. , Baird Taylor N. , Boller Manuel , Edwards Melissa , Hickey Mara , Raffe Marc R.
Published: April 2023

Objective

To report summative data from the American College of Veterinary Emergency and Critical Care Veterinary Committee on Trauma (VetCOT) registry.

Design

Multi‐institutional registry data report, April 1, 2017 to December 31, 2019.

Setting

VetCOT identified and verified Veterinary Trauma Centers (VTCs).

Animals

Dogs and cats with evidence of trauma.

Interventions

Data were input to a web‐based data capture system (Research Electronic Data Capture) by data entry personnel trained in data software use and operational definitions of data variables. Data on demographics, trauma type, preadmission care, trauma severity assessment at presentation (modified Glasgow Coma Scale and Animal Trauma Triage score), key laboratory parameters, interventions, and case outcome were collected. Summary descriptive data for each species are reported.

Measurements and Main Results

Thirty‐one VTCs contributed data from 20,842 canine and 4003 feline trauma cases during the 33‐month reporting period. Most cases presented directly to a VTC (82.1% dogs, 82.1% cats). Admission to hospital rates were slightly lower in dogs (27.8%) than cats (32.7%). Highest mortality rates by mechanism of injury in dogs were struck by vehicle (18.3%), ballistic injury (17.6%), injured inside vehicle (13.2%), nonpenetrating bite wound (10.2%), and choking/pulling injury (8.5%). Highest mortality rates by mechanism of injury in cats were struck by vehicle (43.3%), ejected from vehicle (33.3%), nonpenetrating bite wound (30.7%), ballistic injury (27.8%), and choking/pulling injury (25.0%). The proportion of animals surviving to discharge was 93.1% (dogs) and 82.5% (cats).

Conclusions

The VetCOT registry is a powerful resource for collection of a large dataset on trauma in dogs and cats seen at VTCs. Overall survival to discharge was high indicating low injury severity for most recorded cases. Further evaluation of data on subsets of injury types, patient assessment parameters, interventions, and associated outcome are warranted. Data from the registry can be leveraged to inform clinical trial design and justification for naturally occurring trauma as a translational model to improve veterinary and human trauma patient outcome.