bluuebunny/crossref_metadata_2025 huggingface dataset:
Psychological impact of simple scoring system for predicting early pregnancy outcome in pregnancy of uncertain viability: randomized controlled trial
Authors: Lawson K. , Bourne T. , Bottomley C.
Published: December 2022

Objective

To investigate whether psychological wellbeing of women with an intrauterine pregnancy of uncertain viability can be modified during the waiting period to final diagnosis, by offering predictive information regarding the likely outcome of the pregnancy (chance of ongoing viability).

Methods

This was a single‐center two‐arm randomized controlled trial conducted over 18 months at a teaching hospital in London, UK. Consecutive eligible women attending the early pregnancy assessment unit with an interim ultrasound finding of intrauterine pregnancy of uncertain viability were recruited. All women were offered a follow‐up ultrasound scan after 14 days. Participants were randomized to receive a prediction score for ongoing viability at 14 days or routine care (control). Anxiety, depression and worry symptoms were assessed using validated self‐report questionnaires (hospital anxiety and depression scale (HADS), Penn state worry questionnaire (PSWQ)) prior to randomization and at two further timepoints during the waiting period preceding final diagnosis. The change in psychological scores over the study period was analyzed. The secondary outcome was the perceived value of the risk prediction tool reported by participants.

Results

A total of 278 women participated in this study. After adjusting for baseline scores, no difference in anxiety, depression or worry scores was demonstrated between control and intervention groups at either timepoint. Subgroup analysis, first of women with high initial anxiety (HADS > 11) or worry (PSWQ ≥ 45), and second of women with a more favorable predicted prognosis (≥ 75% chance of ongoing viability), demonstrated no difference between intervention and control groups. Despite this, 76/110 (69.1% (95% CI, 60.5–78.4%)) women who provided feedback in the intervention group found it to be helpful and 97/110 (88.2% (95% CI, 81.0–93.7%)) reported that they would use the tool again.

Conclusion

Current prediction tools may be useful for healthcare professionals to guide management and optimize utilization of early pregnancy resources. However, in this study, implementation of an accurate tool did not result in an objective measurable benefit to patients in terms of reduction in anxiety, depression and worry symptoms experienced during the waiting period to final outcome compared with women who did not receive a prediction score. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.
Fazit und Ausblick
Authors: Schumacher Mareike K.
Published: December 2022

Im letzten Kapitel dieses Buches werden die drei Haupterrungenschaften dieser Forschungsarbeit zusammengefasst. Es wurde ein fuzzy-set-Modell für literarische Raumdarstellungen eingeführt, das auf einem sechs Kategorien umfassenden System beruht und dynamisch angepasst werden kann. Auf Basis dieses Modells wurde ein Machine-Learning-Classifier trainiert, der Indikatoren narrativer Raumdarstellung automatisch annotieren kann. Schließlich wurde noch eine Formel entwickelt, um literarische Raumdarstellung auf einen Wert zu bringen und sie somit mess- und vergleichbar zu machen. Alle drei Teilergebnisse werden hier in ihrer Relevanz und Anschlussfähigkeit an (digitale) Literaturwissenschaften beschrieben.
Revised FDI criteria for evaluating direct and indirect dental restorations—recommendations for its clinical use, interpretation, and reporting
Authors: Hickel Reinhard , Mesinger Sabine , Opdam Niek , Loomans Bas , Frankenberger Roland , Cadenaro Milena , Burgess John , Peschke Arnd , Heintze Siegward D. , Kühnisch Jan
Published: December 2022

Objectives

The FDI criteria for the evaluation of direct and indirect dental restorations were first published in 2007 and updated in 2010. Meanwhile, their scientific use increased steadily, but several questions from users justified some clarification and improvement of the living document.

Materials and methods

An expert panel (N = 10) initiated the revision and consensus process that included a kick-off workshop and multiple online meetings by using the Delphi method. During and after each round of discussion, all opinions were collected, and the aggregated summary was presented to the experts aiming to adjust the wording of the criteria as precisely as possible. Finally, the expert panel agreed on the revision.

Results

Some categories were redefined, ambiguities were cleared, and the descriptions of all scores were harmonized to cross-link different clinical situations with possible management strategies: reviewing/monitoring (score 1–4), refurbishment/reseal (score 3), repair (score 4), and replacement (score 5). Functional properties (domain F: fracture of material and retention, marginal adaptation, proximal contact, form and contour, occlusion and wear) were now placed at the beginning followed by biological (domain B: caries at restoration margin, hard tissue defects, postoperative hypersensitivity) and aesthetic characteristics (domain A: surface luster and texture, marginal staining, color match).

Conclusion

The most frequently used eleven categories of the FDI criteria set were revised for better understanding and handling.

Clinical relevance

The improved description and structuring of the criteria may help to standardize the evaluation of direct and indirect restorations and may enhance their acceptance by researchers, teachers, and dental practitioners.
Optical Ammonia-Sensing Probe Based on Surface-Plasmon Resonance of Silver-Nanoparticle-Decorated Superparamagnetic Dendritic Nanoparticles
Authors: Abdelaziz Omar A. , Abdallah Rawan M. , Khater Rawya A. , Abo Dena Ahmed S. , El-Sherbiny Ibrahim M.
Published: December 2022

Ammonia is a serious contaminant of aquaculture water due to its continuous release into the water environment during the biological processes of aquatic animals. Ammonia accumulation in water has negative environmental impacts, including eutrophication and the death of aquatic organisms. Therefore, sensitive and accurate determination of ammonia is an urgent need, especially in pisciculture systems. Here, we report the fabrication of a novel magnetic–hyperbranched nanomaterial-based ammonia-sensing probe for the fast and sensitive determination of ammonia in water. The proposed probe is composed of poly(amidoamine) (PAMAM)-coated superparamagnetic iron oxide nanoparticles (SPIONs) decorated with silver nanoparticles. Changing the ammonia concentration is associated with a corresponding change in the surface plasmon resonance property of silver nanoparticles. The proposed nanosystem was characterized with FTIR spectroscopy, SEM imaging, energy-dispersive X-ray (EDX) analysis, TEM imaging, X-ray diffractometry (XRD), and vibrating sample magnetometry (VSM). The TEM images showed a homogenous and uniform distribution of the nanoparticles with an average nanoparticle size of 200 nm, while the surface silver nanoparticles have an average particle size of 10–50 nm. The proposed optical ammonia sensor was successfully used to determine the concentration of ammonia in water samples by measuring the change in the solution absorbance at 428 nm. The obtained results revealed high recovery values (96.3–104.7%) and very low detection (LOD = 5.69 mg/L) and quantification (LOQ = 18.96 mg/L) limits. The standard plot is linear in the concentration range of 10–50 mg/L with an r2 value of 0.9980. Sandell’s sensitivity of the most promising sensor (NP-III) among the investigated systems was found to be 0.15 µg/cm2, which indicates high sensitivity.
Tumor P70S6K hyperactivation is inversely associated with tumor-infiltrating lymphocytes in triple-negative breast cancer
Authors: Jimeno Rebeca , Mouron Silvana , Salgado Roberto , Loi Sherene , Pérez-Mies Belén , Sánchez-Bayona Rodrigo , Manso Luis , Martínez Mario , Garrido-García Ana , Serrano-Pardo Rosario , Colomer Ramón , Quintela-Fandino Miguel
Published: December 2022

Purpose

Triple-negative breast cancer (TNBC) is characterized by large heterogeneity and relative lack of available targeted therapies. To find therapeutic strategies for distinct patients with TNBC, several approaches have been used for TNBC clustering, including recently immune and phosphoproteomic patterns. Based on 70-kDa ribosomal protein S6 kinase (P70S6K)-TNBC clustering, the current study explores the immune profiling in TNBC tumors.

Methods

Stromal tumor-infiltrating lymphocytes (sTILs) were evaluated in human TNBC tumor samples. Furthermore, immunohistochemistry staining for CD8, CD4, Foxp3, and CD20 was performed in tissue microarrays (TMA) sections.

Results

Histological analysis showed decreased sTILs, CD20+ cells, and CD8+/CD4+ ratio in high phosphorylated P70S6K (p-P70S6K) tumors. Moreover, p-P70S6K score was directly correlated with CD4+ and Foxp3+ T cells, while it was inversely correlated with CD8+/CD4+ and CD8+/Foxp3+ ratios.

Conclusion

sTIL infiltration and lymphocyte profiling vary in the context of hyperactivation of P70S6K in TNBC tumors.
Unlocking India’s Potential in Managing Endocrine-Disrupting Chemicals (EDCs): Importance, Challenges, and Opportunities
Authors: Sharma Brij Mohan , Scheringer Martin , Chakraborty Paromita , Bharat Girija K. , Steindal Eirik Hovland , Trasande Leonardo , Nizzetto Luca
Published: December 2022

Endocrine-disrupting chemicals (EDCs) are a prime concern for the environment and health globally. Research shows that in developing countries such as India both the environment and human populations are severely exposed to EDCs and consequently experience rising incidents of adverse health effects such as diabetes and cancers. In this paper, we discuss the current EDC management approach in India, critically assess its limitations, and describe opportunities for potential improvements. Foremost, current EDC management actions and interventions in India are fragmented and outdated, and far behind the modern and comprehensive approaches adopted in the European Union and other developed countries. Strong and well-planned actions are required on various fronts of science, policy, commerce, and public engagement. These actions include the adoption of a dedicated and modern regulatory framework for managing EDCs, enhancing capacity and infrastructure for EDC monitoring in the environment and human population, employing public–private partnership programs for not only managing EDCs but also in the sectors that indirectly contribute toward the mismanagement of EDCs in the country, and raising awareness on EDCs and promoting health-preserving consumption habits among the public. As India hosts a large proportion of the global human population and biodiversity, the success or failure of its actions will substantially affect the direction of global efforts to manage EDCs and set an example for other developing countries.
Impact of the COVID-19 kindergarten closure on overweight and obesity among 3- to 7-year-old children
Authors: Long Xiang , Li Xing-Ying , Jiang Hong , Shen Lian-Di , Zhang Li-Feng , Pu Zheng , Gao Xia , Li Mu
Published: December 2022

Background

Knowledge on the impact of the temporary kindergarten closure policy under COVID-19 in 2020 on childhood overweight and obesity is inadequate. We aimed to examine differences in rates of overweight and obesity from 2018 to 2021 among kindergarten children aged 3–7 years.

Methods

Overweight was defined as body mass index (BMI) > 1 standard deviation (SD) for age and sex, and obesity was defined as BMI > 2 SD for age and sex. Generalized linear mixed modeling was used for analysis.

Results

A total of 44,884 children and 71,216 growth data points from all 57 public kindergartens in Jiading District, Shanghai, China were analyzed. The rates of obesity from 2018 to 2021 were 6.9%, 6.6%, 9.5%, and 7.3% in boys and 2.8%, 2.8%, 4.5%, and 3.1% in girls, respectively. The rates of overweight from 2018 to 2021 were 14.3%, 14.3%, 18.2%, and 15.3% in boys and 10.6%, 10.9%, 13.9%, and 11.6% in girls. The rates of obesity and overweight among kindergarten children in 2020 were significantly higher than those in 2018, 2019, and 2021. Compared to 2020, the odds ratios of the obesity rate in 2018, 2019, and 2021 were 0.67 [95% confidence interval (CI) = 0.58–0.77, P < 0.001], 0.72 (95% CI = 0.64–0.80, P < 0.001) and 0.81 (95% CI = 0.72–0.92, P = 0.001), respectively. The odds ratios of the overweight rate in 2018, 2019, and 2021 were 0.75 (95% CI = 0.69–0.82, P < 0.001), 0.78 (95% CI = 0.72–0.84, P < 0.001), and 0.89 (95% CI = 0.81–0.97, P = 0.008), respectively, compared to 2020.

Conclusions

The rates of overweight and obesity significantly increased among kindergarten children in 2020 after the 5-month kindergarten closure. It was critical to provide guidance to caregivers on fostering a healthy lifestyle for children at home under public health emergencies.
Psychological Distress During the Coronavirus Disease 2019 Pandemic and Associated Factors Among Undergraduate Students in Japan
Authors: Sato Yukihiro , Yatsuya Hiroshi , Saijo Yasuaki , Yoshioka Eiji , Tabuchi Takahiro
Published: December 2022

Objective:

This cross-sectional study aimed to examine factors potentially associated with psychological distress among undergraduate students during the coronavirus disease 2019 pandemic in Japan.

Methods:

We analyzed data of 958 undergraduates (median age 20 y; 56.8% women) from a Web-based, self-administered questionnaire survey conducted from August to September 2020. Prevalence ratios (PRs) for psychological distress defined as 5 points or over of the Kessler Psychological Distress Scale (K6) were calculated by Poisson regression models.

Results:

The proportion of psychological distress was 40.0%. In the mutually-adjusted model, the following were significantly associated with psychological distress: decreases in household income to 50-99% of the prepandemic amount compared with no change (PR = 1.48), newly experiencing unpaid wages compared with no experience (PR = 1.44), insufficient money to buy necessities compared with no shortage (PR = 1.45), receiving a student loan or scholarship compared with none (PR = 1.27), and communication 1 to 3 times a month compared with at least once a week (PR = 1.22). In contrast, school closure during the pandemic compared with no closure was inversely associated with psychological distress (PR = 0.78).

Conclusions:

Among undergraduate students in Japan, economic difficulties significantly predicted psychological distress.
Cash Induced Demand
Authors: Chen Huaizhi
Published: December 2022

I show that cash distributions through cash mergers, dividend payments, and stock buybacks are, in principle, similar to investor fund flows in generating demand for investable assets. Abnormal returns on certain assets can be forecasted because delegated investors predictably reinvest cash returns toward certain holdings. Novel measures of stock-level demand constructed using proportional reinvestments by mutual funds predict abnormal returns and issuances in noncash-paying stocks. These results highlight an alternative and substantial source of price fluctuations in the cross section of equities.
The isolated symptom of unilateral tonsillar enlargement has limited value in adults with a suspected head and neck cancer pathway
Authors: Lau K L , Rajgor A , Muzammil A , Scurrah R , Cocks H , Oozeer N
Published: December 2022

Objective

Given the uncertainty regarding the predictive value of unilateral tonsillar enlargement and/or lesion in malignancies, this study aimed to evaluate the efficacy of unilateral tonsillar enlargement and/or lesion referral criterion in the adult suspected head and neck cancer pathway.

Methods

All two-week wait referrals received in 2018–2019 were reviewed. All patients referred with unilateral tonsillar enlargement and/or lesion were included and analysed for patient demographic data, presenting symptoms, initial clinic outcomes and final diagnoses.

Results

A total of 4934 urgent head and neck cancer referrals were analysed, and 1.9 per cent of these had unilateral tonsillar enlargement and/or lesion. Only 10 patients were diagnosed with tonsil cancer. All the positive tonsil cancer cases had at least one additional head and neck red flag symptom.

Conclusion

The referral criterion for unilateral tonsillar enlargement and/or lesion may be of limited benefit in an already economically challenged National Health Service. Further multicentre studies should be undertaken to refine conclusions on the value of unilateral tonsillar enlargement and/or lesion alone as a criterion for the head and neck cancer two-week wait pathway.
Editorial: food and nutrition: pathways to a sustainable future
Authors: Paxman Jenny R. , Nield Lucie
Published: December 2022

The world is waking up to the reality of climate change and the challenge of feeding 10 billion people in a healthy and sustainable way. For population and planetary health, food systems need to change. ‘Food and nutrition: pathways to a sustainable future’ was the first face-to-face Nutrition Society Summer Conference since 2018, bringing together leading contributors from across the globe to explore six pathways to a better tomorrow. Review papers from the conference symposia cut across disciplinary divides showcasing advances in scientific methods and our cumulative understanding of the impact of the food system on climate change. The depth, breadth and advancement of research presented demonstrate the power of collaborative research that can shape industry, individual and population recommendations and create a powerful shift towards the sustainable dietary patterns and systems that are so urgently required.
Ontogenetic and spatial variability in parasite communities of white shrimp Penaeus setiferus (Decapoda: Penaeidae)
Authors: Zuidema Sarah R. , de Buron Isaure , Kingsley-Smith Peter R. , Hill-Spanik Kristina M. , Fanani Natalia , Kendrick Michael R.
Published: December 2022

Understanding the combined effects of multi-parasite infections on their hosts is necessary for documenting parasite impacts and is particularly important for developing effective management strategies for economically important organisms. The white shrimp Penaeus setiferus supports important recreational and commercial fisheries along the southeastern and Gulf coasts of the United States and occupies an important ecological niche in estuarine and offshore habitats throughout these regions. The goal of this study was to identify and assess ontogenetic and spatial variation in white shrimp parasite communities and their relation to shrimp health. We used a series of trawl surveys in tidal creek and open water habitats of an estuary in the southeastern USA to collect and identify parasites of white shrimp using morphological and DNA sequencing techniques. Parasite communities in white shrimp were composed of organisms belonging to 6 classes: Conoidasida (gregarines), Oligohymenophorea (apostome and sessilid ciliates), Microsporea (meiodihaplophasids), Chromadorea (rhabditids), Cestoda (cyclophyllideans, lecanocephalideans and trypanorhynchs) and Trematoda (plagiorchiids). Parasite communities differed significantly among white shrimp life stages and localities. Furthermore, the health condition known as black gill occurred in some shrimp and was significantly related to parasite community structure. Infection metrics for the apostome ciliate Hyalophysa lynni, the trypanorhynch larvae Prochristianella sp. and the rhabditid larvae Hysterothylacium sp. were significantly different between shrimp exhibiting and not exhibiting black gill. These results highlight the importance of understanding parasite communities and the potential interactive effects of multiple parasite infections on shrimp health.
Public policies and social progress: two evaluation models
Authors: Fernandes Reynaldo
Published: December 2022

The article presents two models of public policy evaluation: one named idealistic and the other named pragmatic. In the former, social progress occurs when changes in the form of how society is organised bring us closer to social institutions and public authority conduct considered ideal. In the latter, social progress occurs if the prevailing social state (postchanges) is taken to be better than the previous social state (prechanges), according to certain pre-established judgement criteria. It is argued that the adoption of different models is one of the main obstacles to clarity in the public debate on the implementation of public policies, namely, that of making the points of disagreement explicit. The article presents a defence of the pragmatic model, which is considered more compatible with the use of scientific criteria in order to assess the effectiveness of policies.
Real-world flexibility in adolescent girls’ emotion regulation strategy selection: An investigation of strategy switching
Authors: McKone Kirsten M.P. , Edershile Elizabeth A. , Ladouceur Cecile D. , Silk Jennifer S.
Published: December 2022

Adolescence is an important stage for the development of emotion regulation skills, especially for adolescent girls who are at elevated risk for the development of depression and anxiety. Although some emotion regulation strategies are more effective at helping adolescents regulate negative affect on average, research indicates strategy effectiveness varies with the context in which a strategy is deployed. Yet less work has been done examining which contextual factors are associated with adolescents switching emotion regulation strategies in their daily lives. This study examined individual and contextual factors related to negative interpersonal events that are associated with strategy effectiveness, including age, emotional intensity, perceived controllability, and co-regulatory support, and their association with adolescent emotion regulation strategy switching in daily life via ecological momentary assessment. Results indicated that adolescent girls differed in the degree to which they altered their emotion regulation strategies throughout their daily lives, and that switching strategies was associated with age as well as individual and within-person differences in perceived controllability, emotional intensity, and co-regulatory support. This study provides critical proof-of-concept of the utility of emotion regulation strategy switching as a measure of regulatory flexibility and highlights regulatory processes that may hold clues to the mechanisms of developmental psychopathology.
Why does children’s temperamental exuberance increase their vulnerability to externalizing symptoms? A process-oriented approach
Authors: Davies Patrick T. , Cao Vanessa T. , Patel Meera D. , Sturge-Apple Melissa L.
Published: December 2022

This study examined children’s exposure to family adversity, hostile reactivity to parental conflict, and negative family representations as mediators of the prospective relation between their temperamental exuberance and externalizing symptoms. Participants included 243 preschool children (Mage = 4.60 years; 56% girls) and parents (48% Black; 16% Latinx) in a multi-method and multi-informant study with three annual measurement occasions. Structural equation model results specifically supported children’s hostile reactivity to parental conflict and negative family representations as mediators. Exuberance predicted residualized increases in children’s hostile reactivity and negative family representations over a 1-year period. In turn, children’s hostile reactivity and negative family representations predicted their greater externalizing symptoms 1 year later after controlling for prior externalizing symptoms. Results are discussed in the context of their relation and refinement of temperamental models of developmental psychopathology.
A Response to Zambrano
Authors: Harris John
Published: December 2022

Alexander Zambrano sets out to refute an argument that I have made on a number of occasions over many years since 1992, which he calls “Harris’s Greater Need Argument” (2002).
Princely urbanism and the colonial city: Bombay, c. 1860–1940s
Authors: Boehme Kate
Published: December 2022

To this point, nineteenth-century Bombay – including its urban development, economy and population – has most often been analysed in relation to the city's position within British imperial, and overseas maritime, networks. In contrast, this article calls into question established scholarly definitions of ‘colonial’ and ‘princely’ spaces in nineteenth- and early twentieth-century India, through an in-depth examination of Bombay's socio-economic ties with wider Indian networks. It focuses on connections that stretched across colonial borders and into the princely states, suggesting that both the city's economy and its business elite were rooted in cross-border Indian capital networks. It further highlights the contributions of Indian princes, their states and populations to the development of urban culture in Bombay.
Chylous pericardial effusion with cardiac tamponade in a child treated with imatinib
Authors: Donovan Denis J. , Siskind Tamar , Thanjan Maria T. , Holzer Ralf J. , Dayton Jeffrey D. , Carroll Sheila J.
Published: December 2022

Chylous pericardial effusions are extremely rare outside of thoracic and cardiac surgery patients. We report the case of an 8-year-old girl with history of recurrent benign giant cell granulomas who developed a large chylous pericardial effusion with cardiac tamponade soon after beginning therapy with imatinib. In this article, we discuss the presentation, diagnosis, and management and review the published literature of this rarely reported side effect of this medication.
Informality and Politics in the Global South: Three Perspectives
Authors: Post Alison E.
Published: December 2022

Informality is often studied by scholars of urban studies but has received comparatively little attention by political scientists. This is surprising given the fact that large portions of the world’s population live, work, or transfer funds informally. The conventional wisdom is that the informal economy—the portion of the economy operating outside the regulatory reach of the state—is not very political because informal sector workers are relatively atomized and find collective action to be costly. The three books reviewed here, however, demonstrate that the informal sector is not only characterized by important forms of political organization but also affects politics within government institutions—and can even contribute to regime downfall. Calla Hummel’s Why Informal Workers Organize and Shelby Grossman’s Politics of Order in Informal Markets examine organization among informal sector workers, with Hummel probing the circumstances under which organization occurs and Grossman when such organizations are effective. In Black Markets and Militants, Medani takes the opposite perspective, examining how informal financial flows and networks affect state regulatory capacity. These three books marshal significant amounts of original data, pointing to how future research on these important dynamics can be conducted.
Using Health Intervention Messages to Reduce Intentions to Spend Time	on Social Networks
Authors: Rose Angela , Brannon Laura A.
Published: December 2022

Abstract: This study examined the efficacy of using behavioral feedback and social norms health message interventions to reduce social networking site (SNS) use. A total of 107 participants reported their current SNS use and attitude through endorsement of the statement “I spend too much time on social media” before being randomly assigned to read a message (control, generic consequences, social norms, or behavioral feedback). After reading the message, participants reported their future intentions to use social media and responded to the statement again. The results demonstrated a relationship between the social norms message and future intended SNS use, such that those who read information about the norm for SNS use were more likely to report that they intended to reduce their SNS use in the future. An interaction suggested that the higher the current use, the more effective it was to expose the user to the social norm. Additionally, an association was found between the behavioral feedback message and the belief that they were currently using SNSs too much, such that those who saw tailored consequences of their use were more likely to endorse the statement more strongly. Overall, using these health messages as an intervention to reduce SNS use is a promising avenue that should be explored further.
Phenotype-based screening rediscovered benzopyran-embedded microtubule inhibitors as anti-neuroinflammatory agents by modulating the tubulin–p65 interaction
Authors: Yim Junhyeong , Lee Jaeseok , Yi Sihyeong , Koo Ja Young , Oh Sangmi , Park Hankum , Kim Seong Soon , Bae Myung Ae , Park Jongmin , Park Seung Bum
Published: December 2022

Neuroinflammation is one of the critical processes implicated in central nervous system (CNS) diseases. Therefore, alleviating neuroinflammation has been highlighted as a therapeutic strategy for treating CNS disorders. However, the complexity of neuroinflammatory processes and poor drug transport to the brain are considerable hurdles to the efficient control of neuroinflammation using small-molecule therapeutics. Thus, there is a significant demand for new chemical entities (NCEs) targeting neuroinflammation. Herein, we rediscovered benzopyran-embedded tubulin inhibitor 1 as an anti-neuroinflammatory agent via phenotype-based screening. A competitive photoaffinity labeling study revealed that compound 1 binds to tubulin at the colchicine-binding site. Structure–activity relationship analysis of 1’s analogs identified SB26019 as a lead compound with enhanced anti-neuroinflammatory efficacy. Mechanistic studies revealed that upregulation of the tubulin monomer was critical for the anti-neuroinflammatory activity of SB26019. We serendipitously found that the tubulin monomer recruits p65, inhibiting its translocation from the cytosol to the nucleus and blocking NF-κB-mediated inflammatory pathways. Further in vivo validation using a neuroinflammation mouse model demonstrated that SB26019 suppressed microglial activation by downregulating lba-1 and proinflammatory cytokines. Intraperitoneal administration of SB26019 showed its therapeutic potential as an NCE for successful anti-neuroinflammatory regulation. Along with the recent growing demands on tubulin modulators for treating various inflammatory diseases, our results suggest that colchicine-binding site-specific modulation of tubulins can be a potential strategy for preventing neuroinflammation and treating CNS diseases.
Effect of chromatin modifiers on the plasticity and immunogenicity of small-cell lung cancer
Authors: Kirk Nicole A. , Kim Kee-Beom , Park Kwon-Sik
Published: December 2022

Tumor suppressor genes (TSGs) are often involved in maintaining homeostasis. Loss of tumor suppressor functions causes cellular plasticity that drives numerous types of cancer, including small-cell lung cancer (SCLC), an aggressive type of lung cancer. SCLC is largely driven by numerous loss-of-function mutations in TSGs, often in those encoding chromatin modifiers. These mutations present a therapeutic challenge because they are not directly actionable. Alternatively, understanding the resulting molecular changes may provide insight into tumor intervention strategies. We hypothesize that despite the heterogeneous genomic landscape in SCLC, the impacts of mutations in patient tumors are related to a few important pathways causing malignancy. Specifically, alterations in chromatin modifiers result in transcriptional dysregulation, driving mutant cells toward a highly plastic state that renders them immune evasive and highly metastatic. This review will highlight studies in which imbalance of chromatin modifiers with opposing functions led to loss of immune recognition markers, effectively masking tumor cells from the immune system. This review also discusses the role of chromatin modifiers in maintaining neuroendocrine characteristics and the role of aberrant transcriptional control in promoting epithelial-to-mesenchymal transition during tumor development and progression. While these pathways are thought to be disparate, we highlight that the pathways often share molecular drivers and mediators. Understanding the relationships among frequently altered chromatin modifiers will provide valuable insights into the molecular mechanisms of SCLC development and progression and therefore may reveal preventive and therapeutic vulnerabilities of SCLC and other cancers with similar mutations.
Structural mechanism of signal transduction in a phytochrome histidine kinase
Authors: Wahlgren Weixiao Yuan , Claesson Elin , Tuure Iida , Trillo-Muyo Sergio , Bódizs Szabolcs , Ihalainen Janne A. , Takala Heikki , Westenhoff Sebastian
Published: December 2022

Phytochrome proteins detect red/far-red light to guide the growth, motion, development and reproduction in plants, fungi, and bacteria. Bacterial phytochromes commonly function as an entrance signal in two-component sensory systems. Despite the availability of three-dimensional structures of phytochromes and other two-component proteins, the conformational changes, which lead to activation of the protein, are not understood. We reveal cryo electron microscopy structures of the complete phytochrome from Deinoccocus radiodurans in its resting and photoactivated states at 3.6 Å and 3.5 Å resolution, respectively. Upon photoactivation, the photosensory core module hardly changes its tertiary domain arrangement, but the connector helices between the photosensory and the histidine kinase modules open up like a zipper, causing asymmetry and disorder in the effector domains. The structures provide a framework for atom-scale understanding of signaling in phytochromes, visualize allosteric communication over several nanometers, and suggest that disorder in the dimeric arrangement of the effector domains is important for phosphatase activity in a two-component system. The results have implications for the development of optogenetic applications.
Bioenergetic control of soil carbon dynamics across depth
Authors: Henneron Ludovic , Balesdent Jerôme , Alvarez Gaël , Barré Pierre , Baudin François , Basile-Doelsch Isabelle , Cécillon Lauric , Fernandez-Martinez Alejandro , Hatté Christine , Fontaine Sébastien
Published: December 2022

Soil carbon dynamics is strongly controlled by depth globally, with increasingly slow dynamics found at depth. The mechanistic basis remains however controversial, limiting our ability to predict carbon cycle-climate feedbacks. Here we combine radiocarbon and thermal analyses with long-term incubations in absence/presence of continuously13C/14C-labelled plants to show that bioenergetic constraints of decomposers consistently drive the depth-dependency of soil carbon dynamics over a range of mineral reactivity contexts. The slow dynamics of subsoil carbon is tightly related to both its low energy density and high activation energy of decomposition, leading to an unfavourable ‘return-on-energy-investment’ for decomposers. We also observe strong acceleration of millennia-old subsoil carbon decomposition induced by roots (‘rhizosphere priming’), showing that sufficient supply of energy by roots is able to alleviate the strong energy limitation of decomposition. These findings demonstrate that subsoil carbon persistence results from its poor energy quality together with the lack of energy supply by roots due to their low density at depth.
Ocular tropism of SARS-CoV-2 in animal models with retinal inflammation via neuronal invasion following intranasal inoculation
Authors: Jeong Gi Uk , Kwon Hyung-Jun , Ng Wern Hann , Liu Xiang , Moon Hyun Woo , Yoon Gun Young , Shin Hye Jin , Lee In-Chul , Ling Zheng Lung , Spiteri Alanna G. , King Nicholas J. C. , Taylor Adam , Chae Ji Soo , Kim Chonsaeng , Ahn Dae-Gyun , Kim Kyun-Do , Ryu Young Bae , Kim Seong-Jun , Mahalingam Suresh , Kwon Young-Chan
Published: December 2022

Although ocular manifestations are reported in patients with COVID-19, consensus on ocular tropism of SARS-CoV-2 is lacking. Here, we infect K18-hACE2 transgenic mice with SARS-CoV-2 using various routes. We observe ocular manifestation and retinal inflammation with production of pro-inflammatory cytokines in the eyes of intranasally (IN)-infected mice. Intratracheal (IT) infection results in dissemination of the virus from the lungs to the brain and eyes via trigeminal and optic nerves. Ocular and neuronal invasions are confirmed using intracerebral (IC) infection. Notably, the eye-dropped (ED) virus does not cause lung infection and becomes undetectable with time. Ocular and neurotropic distribution of the virus in vivo is evident in fluorescence imaging with an infectious clone of SARS-CoV-2-mCherry. The ocular tropic and neuroinvasive characteristics of SARS-CoV-2 are confirmed in wild-type Syrian hamsters. Our data can improve the understanding regarding viral transmission and clinical characteristics of SARS-CoV-2 and help in improving COVID-19 control procedures.
Deep transfer learning enables lesion tracing of circulating tumor cells
Authors: Guo Xiaoxu , Lin Fanghe , Yi Chuanyou , Song Juan , Sun Di , Lin Li , Zhong Zhixing , Wu Zhaorun , Wang Xiaoyu , Zhang Yingkun , Li Jin , Zhang Huimin , Liu Feng , Yang Chaoyong , Song Jia
Published: December 2022

Liquid biopsy offers great promise for noninvasive cancer diagnostics, while the lack of adequate target characterization and analysis hinders its wide application. Single-cell RNA sequencing (scRNA-seq) is a powerful technology for cell characterization. Integrating scRNA-seq into a CTC-focused liquid biopsy study can perhaps classify CTCs by their original lesions. However, the lack of CTC scRNA-seq data accumulation and prior knowledge hinders further development. Therefore, we design CTC-Tracer, a transfer learning-based algorithm, to correct the distributional shift between primary cancer cells and CTCs to transfer lesion labels from the primary cancer cell atlas to CTCs. The robustness and accuracy of CTC-Tracer are validated by 8 individual standard datasets. We apply CTC-Tracer on a complex dataset consisting of RNA-seq profiles of single CTCs, CTC clusters from a BRCA patient, and two xenografts, and demonstrate that CTC-Tracer has potential in knowledge transfer between different types of RNA-seq data of lesions and CTCs.
Broad misappropriation of developmental splicing profile by cancer in multiple organs
Authors: Singh Arashdeep , Rajeevan Arati , Gopalan Vishaka , Agrawal Piyush , Day Chi-Ping , Hannenhalli Sridhar
Published: December 2022

Oncogenesis mimics key aspects of embryonic development. However, the underlying mechanisms are incompletely understood. Here, we demonstrate that the splicing events specifically active during human organogenesis, are broadly reactivated in the organ-specific tumor. Such events are associated with key oncogenic processes and predict proliferation rates in cancer cell lines as well as patient survival. Such events preferentially target nitrosylation and transmembrane-region domains, whose coordinated splicing in multiple genes respectively affect intracellular transport and N-linked glycosylation. We infer critical splicing factors potentially regulating embryonic splicing events and show that such factors are potential oncogenic drivers and are upregulated specifically in malignant cells. Multiple complementary analyses point to MYC and FOXM1 as potential transcriptional regulators of critical splicing factors in brain and liver. Our study provides a comprehensive demonstration of a splicing-mediated link between development and cancer, and suggest anti-cancer targets including splicing events, and their upstream splicing and transcriptional regulators.
Charge-transfer interface of insulating metal-organic frameworks with metallic conduction
Authors: Sindhu Pooja , Ananthram K. S. , Jain Anil , Tarafder Kartick , Ballav Nirmalya
Published: December 2022

Downsizing materials into hetero-structured thin film configurations is an important avenue to capture various interfacial phenomena. Metallic conduction at the interfaces of insulating transition metal oxides and organic molecules are notable examples, though, it remained elusive in the domain of coordination polymers including metal-organic frameworks (MOFs). MOFs are comprised of metal centers connected to organic linkers with an extended coordination geometry and potential void space. Poor orbitals overlap often makes these crystalline solids electrical insulators. Herein, we have fabricated hetero-structured thin film of a Mott and a band insulating MOFs via layer-by-layer method. Electrical transport measurements across the thin film evidenced an interfacial metallic conduction. The origin of such an unusual observation was understood by the first-principles density functional theory calculations; specifically, Bader charge analysis revealed significant accumulation and percolation of charge across the interface. We anticipate similar interfacial effects in other rationally designed hetero-structured thin films of MOFs.
An optimized antimicrobial peptide analog acts as an antibiotic adjuvant to reverse methicillin-resistant Staphylococcus aureus
Authors: Chen Xuan , Wu Xiaoping , Wang Shaoyun
Published: December 2022

The misuse of antibiotics in animal protein production has driven the emergence of a range of drug-resistant pathogens, which threaten existing public health security. Consequently, there is an urgent need to develop novel antimicrobials and new infection treatment options to address the challenges posed by the dramatic spread of antibiotic resistance. Piscidins, a class of fish-specific antimicrobial peptides (AMPs), are regarded as promising therapies for biomedical applications. Progress towards potential analogs from the piscidin family has been hampered by unenforceable structural optimization strategies. Here, we leverage a strategy of bioinformatics analysis combined with molecular dynamics (MD) simulation to identify specific functional hotspots in piscidins and rationally design related analogues. As expected, this approach yields a potent and non-toxic PIS-A-1 that can be used as an antibiotic adjuvant to reverse methicillin-resistant Staphylococcus aureus (MRSA) pathogens. Remarkably, the structural optimization scheme and application strategy proposed here will contribute richer therapeutic options for the safe production of animal protein.
Establishment of a meta-analysis based novel aortic dissection mouse model
Authors: Jiang Hongcheng , Liu Wanjun , He Xingwei , Zeng Hesong
Published: December 2022

Aortic dissection (AD) is a life-threatening disease and the detailed mechanism remains unclear. Thus, proper animal models are urgently required to better understand its pathogenesis. Our current study aims to establish a reliable, time and cost-effective mouse AD model. To conduct the meta-analysis, we searched PubMed for related studies up to 2021 and statistical analysis was conducted using Review Manager 5.4. For the animal experiment, 6-week-old male ApoE−/− mice were given β-aminopropionitrile (BAPN) at a concentration of 1 g/L for 3 weeks before being infused with saline, 1000 ng/kg/min or 2500 ng/kg/min angiotensin II (AngII) via osmotic mini pumps for 2 or 4 weeks. To determine the presence of AD, we performed B-ultrasonography, hematoxylin and eosin (H&E) staining, and van Gieson staining. The result of the meta-analysis showed that the use of BAPN and more than 2000 ng/kg/min AngII can increase the rate of AD formation, whereas administrating Ang II for more than 28 days has no significant effect on the rate of AD formation when compared with the less than 14 days group. In the present study, mice treated with BAPN combined with 2500 ng/kg/min AngII for 2 weeks (12/20) had a significantly higher AD formation rate than mice treated with BAPN combined with 1000 ng/kg/min Ang II for 4 weeks (2/10), and had a similar model formation rate compared with the mice treated withβ-aminopropionitrile combined with 2500 ng/kg/min AngII for 4 weeks (6/10). There were 3 mice (3/10) and 6 mice (6/20) who died in the group treated with β-aminopropionitrile combined with 2500 ng/kg/min AngII for 4 weeks and 2 weeks respectively, and only one mouse (1/10) died in the group treated with β-aminopropionitrile combined with 1000 ng/kg/min AngII for 4 weeks. In 6-week-old male ApoE−/− mice that received with 1 g/L BAPN in the drinking water for 3 weeks along with 2500 ng/kg/min AngII infusion via osmotic mini pumps for 2 weeks, the highest model formation rate and relative lower cumulative mortality were noted.
Text-based automatic personality prediction using KGrAt-Net: a knowledge graph attention network classifier
Authors: Ramezani Majid , Feizi-Derakhshi Mohammad-Reza , Balafar Mohammad-Ali
Published: December 2022

Nowadays, a tremendous amount of human communications occur on Internet-based communication infrastructures, like social networks, email, forums, organizational communication platforms, etc. Indeed, the automatic prediction or assessment of individuals’ personalities through their written or exchanged text would be advantageous to ameliorate their relationships. To this end, this paper aims to propose KGrAt-Net, which is a Knowledge Graph Attention Network text classifier. For the first time, it applies the knowledge graph attention network to perform Automatic Personality Prediction (APP), according to the Big Five personality traits. After performing some preprocessing activities, it first tries to acquire a knowing-full representation of the knowledge behind the concepts in the input text by building its equivalent knowledge graph. A knowledge graph collects interlinked descriptions of concepts, entities, and relationships in a machine-readable form. Practically, it provides a machine-readable cognitive understanding of concepts and semantic relationships among them. Then, applying the attention mechanism, it attempts to pay attention to the most relevant parts of the graph to predict the personality traits of the input text. We used 2467 essays from the Essays Dataset. The results demonstrated that KGrAt-Net considerably improved personality prediction accuracies (up to 70.26% on average). Furthermore, KGrAt-Net also uses knowledge graph embedding to enrich the classification, which makes it even more accurate (on average, 72.41%) in APP.
Galleria mellonella immune melanization is fungicidal during infection
Authors: Smith Daniel F. Q. , Dragotakes Quigly , Kulkarni Madhura , Hardwick J. Marie , Casadevall Arturo
Published: December 2022

A key component of the insect immune response is melanin production, including within nodules, or aggregations of immune cells surrounding microbes. Melanization produces oxidative and toxic intermediates that limit microbial infections. However, a direct fungicidal role of melanin during infection has not been demonstrated. We previously reported that the fungusCryptococcus neoformansis encapsulated with melanin within nodules ofGalleria mellonellahosts. Here we developed techniques to study melanin’s role duringC. neoformansinfection inG. mellonella. We provided evidence that in vivo melanin-encapsulation was fungicidal. To further study immune melanization, we applied tissue-clearing techniques to visualize melanized nodules in situ throughout the larvae. Further, we developed a time-lapse microscopy protocol to visualize the melanization kinetics in extracted hemolymph following fungal exposure. Using this technique, we found that cryptococcal melanin and laccase enhance immune melanization. We extended this approach to study the fungal pathogensCandida albicansandCandida auris. We find that the yeast morphologies of these fungi elicited robust melanization responses, while hyphal and pseudohyphal morphologies were melanin-evasive. Approximately 23% of melanin-encapsulatedC. albicansyeast can survive and breakthrough the encapsulation. Overall, our results provide direct evidence that immune melanization functions as a direct antifungal mechanism inG. mellonella.