bluuebunny/crossref_metadata_2025 huggingface dataset:
Pollen-borne ilarviruses of peach: biology, ecology, and disease management
Authors: Tayal Mandeep , Rodriguez Bonilla Fabian , Powell Garner , Cieniewicz Elizabeth
Published: June 2024

Prunus necrotic ringspot virus (PNRSV) and prune dwarf virus (PDV) are pollen-transmitted ilarviruses that affect stone fruits. Both viruses are widespread in peach orchards in the southeastern United States. Although symptoms may not always be present, typical symptoms of PNRSV infection in peaches include stunting, chlorosis, and decline of the tree over time, while PDV infection is associated with stunted growth and shortened internodes. Co-infection with PNRSV and PDV can lead to peach stunt disease, causing yield losses of up to 55%. Here we provide information on the diagnostic methods currently available with considerations for selecting the best method based on plant tissue, sampling season, sample number, and cost. The ecology of PNRSV and PDV, including their movement within and between plants and the role of wild hosts as reservoirs, is also discussed. Both PNRSV and PDV are primarily transmitted through vegetative propagation and pollen; the latter could be horizontal between co-occurring blooming trees and/or vertical from parent to progeny. Certain insect groups play a role in spreading PNRSV and PDV in greenhouse and field settings. Management strategies to prevent virus spread, including clean plant programs which provide virus-negative propagation materials, and cultural management practices, such as removing infected trees, are emphasized to prevent secondary spread. While practical challenges persist in managing infection sources and wild hosts, proactive measures are essential to mitigate the spread of PNRSV and PDV and safeguard the peach industry.
An Unseen Amphetamine Epidemic in West Africa, 1960–1980
Authors: Daly Samuel Fury Childs
Published: June 2024

From the early 1960s to the late 1970s, a massive trade in the stimulant known as “speed” took place from the United Kingdom to Nigeria. British manufacturers sold West African pharmacists hundreds of millions of doses of dexamphetamine sulphate, and the British government made a long and mostly ineffectual attempt to stop them. The dexamphetamine trade fed an epidemic of addiction caused by economic precarity and climate change. Students took it to study through the night, and cattle herders used it to drive their herds greater distances as drought shrunk their pastures. Amphetamine dependency went mostly unnoticed at the time, but it had lasting consequences. Stimulants were an anomaly in the broader political economy of postcolonial Africa, and dexamphetamine was a counterpoint to the later history of the cocaine trade from Africa to Europe. In the 1980s, cocaine would flow in the other direction—from Lagos to London—much to the ire of the British government. But for many years, the United Kingdom was not the destination for Nigeria’s illicit drugs—it was their source.
Tomorrow and the Day After in Semitic
Authors: Rubin Aaron D
Published: June 2024

No word for ‘tomorrow’ can be reconstructed for Proto-Semitic, and the attested words in both the ancient and modern languages vary greatly. Despite the prodigious variation and repeated innovation that we find, almost every attested word for ‘tomorrow’ has developed along the same semantic pathway, namely, from a word or root meaning ‘morning’ or ‘dawn’. Semitic languages also have special adverbs (or adverbial phrases) for ‘the day after tomorrow’, and sometimes even for days beyond that, and these exhibit a wider range of sources.
Falling Down and Apart: Post-Orientalism and Iranian American Identity in Sons and Other Flammable Objects
Authors: Shelat Jay Nitin
Published: June 2024

This article theorizes how post-Orientalism—what I term the racialization processes that render Muslims terroristic based on monolithic assumptions—temporally tethers anti-Iranian hate from the late 1970s into the present day. Reading Porochista Khakpour’s 2007 novel Sons and Other Flammable Objects as a case study, I argue that identity is depicted as in freefall because of how post-Orientalist paradigms shape the social and legal reception of Iranian Americans. More specifically, Khakpour illustrates the personal-political contestations of identity in the novel through instances and images of falling. I claim that tumbles, falls, and collapses convey the lack of control the Iranian American characters, especially protagonist Xerxes, have in shaping their own identities against dominating racializing structures. Ultimately, Khakpour’s novel uncovers the multiple ways in which post-Orientalism infiltrates and reorganizes intimate spheres and relationships, making inextricable the personal and political.
“An Actual Experience of Finality”: Melodramatic Retention and Generative Discomfort in Branden Jacobs-Jenkins’s An Octoroon
Authors: Williamson Em
Published: June 2024

The focus of this piece is on Branden Jacobs-Jenkins’s retention and appropriation of melodramatic convention in his 2014 play An Octoroon. By examining how Jacobs-Jenkins alters melodramatic convention, especially the scene-ending tableaux he adapts from Dion Boucicault’s original The Octoroon (1859), this essay asserts that An Octoroon utilizes such outmoded theatrical technique as a means to engender a more contemporary sense of self-reflection in the audience. In this way, Jacobs-Jenkins’s adaptation does not so much send up the antebellum racism on display in Boucicault’s work but rather contemporary modes of racist thinking.
Phase II clinical trial of docetaxel and trastuzumab for HER2-positive advanced extramammary Paget’s disease (EMPD-HER2DOC)
Authors: Hirai Ikuko , Tanese Keiji , Nakamura Yoshio , Fukuda Keitaro , Ouchi Takeshi , Hayashida Tetsu , Kameyama Kaori , Abe Takayuki , Amagai Masayuki , Funakoshi Takeru
Published: June 2024

Background

No consensus has been reached regarding the optimal chemotherapy for metastatic extramammary Paget’s disease (EMPD), a rare cutaneous adenocarcinoma, because of the lack of solid evidence from prospective trials. However, the immunohistochemical profile of EMPD reportedly resembles that of breast cancer, particularly in terms of human epidermal growth factor receptor 2 (HER2) expression, suggesting that HER2 is a promising therapeutic target for advanced HER2-positive EMPD.

Methods

In this phase II single-arm trial, 13 Japanese patients received intravenous trastuzumab (loading dose of 8 mg/kg and maintenance dose of 6 mg/kg) and docetaxel (75 mg/m2) every 3 weeks for up to 2 years. The docetaxel dose was reduced or discontinued according to its toxicity. The primary trial endpoints were objective response rate (ORR) after 3 cycles of treatment and safety throughout the study period.

Results

All 13 patients completed 3 cycles of combination therapy. The median follow-up was 27.9 months. The ORR was 76.9% (n = 10/13; 90% CI, 50.5-93.4). Frequently observed adverse events were neutropenia (100%), hypoalbuminemia (84.6%), and mucocutaneous infection (84.6%), all of which were well tolerated.

Conclusion

The combination of docetaxel and trastuzumab demonstrated a favorable clinical effect and acceptable tolerability, which makes it a good treatment option for HER2-positive metastatic EMPD (ClinicalTrials.gov Identifier: UMIN000021311, jRCTs031180073).
The Economic Consequences of Legal Framework
Authors: Karkalakos Sotiris
Published: June 2024

The legal origins of a state do influence significantly its economic growth. The current work verifies that countries whose legal framework is based on common law tend to have better economic results compared to countries based on civil law. It investigates the role of an effective regulatory framework in promoting economic growth and development in recent years. Regulation can have potentially significant macroeconomic consequences by helping or hampering the dynamics of economic restructuring and resource reallocation that characterize the growth process. Achieving good regulatory outcomes is almost always a co-operative effort: by the government, regulators, the regulated, and the broader community. In the European Union, the drivers to initiate better regulation strategies, varied from country to country. Nevertheless, economic growth, competitiveness and the needs of businesses have been the prominent reasons for engaging in better regulation policies. This paper has concluded that countries which have actively reformed their legal systems focusing on quality standards succeed in the creation of a solid social and economic environment.
STAT3-induced upregulation of lncRNA TTN-AS1 aggravates podocyte injury in diabetic nephropathy by promoting oxidative stress
Authors: Wang Wenzhe , Li Yongxia , Zhu Fan , Huang Yunfang
Published: June 2024

Background

Diabetic nephropathy (DN) is the most common microvascular complication of diabetes mellitus (DM), being the second cause of end-stage renal disease globally. Podocyte injury is closely associated with DN developmen. Our study aimed to investigate the role of long non-coding RNA (lncRNA) TTN-AS1 in DN-associated podocyte injury.

Methods

The mouse podocyte cell line (MPC5) and human primary podocytes were stimulated by high glucose (HG; 30 nM glucose) to establish the cellular model of DN. Before HG stimulation, both podocytes were transfected with sh-TTN-AS1#1/2 or pcDNA3.1/STAT3 to evaluate the influence of TTN-AS1 knockdown or STAT3 overexpression on HG-induced podocyte injury. TTN-AS1 and STAT3 expression in both podocytes was examined by RT-qPCR. Cell viability and death were assessed by CCK-8 and LDH release assay. ELISA was adopted for testing IL-6 and TNF-α contents in cell supernatants. The levels of oxidative stress markers (ROS, MDA, SOD, and GSH) in cell supernatants were determined by commercial kits. Western blotting was used for measuring the expression of fibrosis markers (fibronectin and α-SMA and podocyte function markers (podocin and nephrin) in podocytes.

Results

HG stimulation led to decreased cell viability, increased cell death, fibrosis, inflammation, cell dysfunction and oxidative stress in podocytes. However, knockdown of TTN-AS1 ameliorated HG-induced podocyte injury. Mechanically, the transcription factor STAT3 interacted with TTN-AS1 promoter and upregulated TTN-AS1 expression. STAT3 overexpression offset the protective effect of TTN-AS1 silencing on HG-induced podocyte damage.

Conclusion

Overall, STAT3-mediated upregulation of lncRNA TTN-AS1 could exacerbate podocyte injury in DN through suppressing inflammation and oxidative stress.
Influenza A genomic diversity during human infections underscores the strength of genetic drift and the existence of tight transmission bottlenecks
Authors: Martin Michael A , Berg Nick , Koelle Katia
Published: June 2024

Influenza infections result in considerable public health and economic impacts each year. One of the contributing factors to the high annual incidence of human influenza is the virus’s ability to evade acquired immunity through continual antigenic evolution. Understanding the evolutionary forces that act within and between hosts is therefore critical to interpreting past trends in influenza virus evolution and in predicting future ones. Several studies have analyzed longitudinal patterns of influenza A virus genetic diversity in natural human infections to assess the relative contributions of selection and genetic drift on within-host evolution. However, in these natural infections, within-host viral populations harbor very few single-nucleotide variants, limiting our resolution in understanding the forces acting on these populations in vivo. Furthermore, low levels of within-host viral genetic diversity limit the ability to infer the extent of drift across transmission events. Here, we propose to use influenza virus genomic diversity as an alternative signal to better understand within- and between-host patterns of viral evolution. Specifically, we focus on the dynamics of defective viral genomes (DVGs), which harbor large internal deletions in one or more of influenza virus’s eight gene segments. Our longitudinal analyses of DVGs show that influenza A virus populations are highly dynamic within hosts, corroborating previous findings based on viral genetic diversity that point toward the importance of genetic drift in driving within-host viral evolution. Furthermore, our analysis of DVG populations across transmission pairs indicates that DVGs rarely appeared to be shared, indicating the presence of tight transmission bottlenecks. Our analyses demonstrate that viral genomic diversity can be used to complement analyses based on viral genetic diversity to reveal processes that drive viral evolution within and between hosts.
Microbiota influence on behavior: Integrative analysis of serotonin metabolism and behavioral profile in germ‐free mice
Authors: Roussin Léa , Gry Elisa , Macaron Mira , Ribes Sandy , Monnoye Magali , Douard Véronique , Naudon Laurent , Rabot Sylvie
Published: June 2024

Previous studies on germ‐free (GF) animals have described altered anxiety‐like and social behaviors together with dysregulations in brain serotonin (5‐HT) metabolism. Alterations in circulating 5‐HT levels and gut 5‐HT metabolism have also been reported in GF mice. In this study, we conducted an integrative analysis of various behaviors as well as markers of 5‐HT metabolism in the brain and along the GI tract of GF male mice compared with conventional (CV) ones. We found a strong decrease in locomotor activity, accompanied by some signs of increased anxiety‐like behavior in GF mice compared with CV mice. Brain gene expression analysis showed no differences in HTR1A and TPH2 genes. In the gut, we found decreased TPH1 expression in the colon of GF mice, while it was increased in the cecum. HTR1A expression was dramatically decreased in the colon, while HTR4 expression was increased both in the cecum and colon of GF mice compared with CV mice. Finally, SLC6A4 expression was increased in the ileum and colon of GF mice compared with CV mice. Our results add to the evidence that the microbiota is involved in regulation of behavior, although heterogeneity among studies suggests a strong impact of genetic and environmental factors on this microbiota‐mediated regulation. While no impact of GF status on brain 5‐HT was observed, substantial differences in gut 5‐HT metabolism were noted, with tissue‐dependent results indicating a varying role of microbiota along the GI tract.
Contact with Wet Cement—A Preventable Cause of Chemical Burn: Case Report and Discussion
Authors: Levine Jeffrey M. , Parekh Nayana S. , Cooper Michael L.
Published: June 2024

Alkali burn from wet cement is an often unrecognized and completely preventable chemical injury. The prevalence of cement burns is likely underestimated because of a lack of awareness and knowledge among both individuals who work with cement and healthcare providers. Chemical injuries have important differences compared with thermal burns: they are usually produced by longer exposure to noxious agents as opposed to short-term exposure that is quickly stopped. As a result, first aid approaches are different.

Chemical burns from cement can be avoided with adequate skin and eye protection as well as immediate first aid if contact occurs. Manufacturers of bagged cement place warning notices on packaging, but these can be small and go unnoticed by consumers. Construction workers and amateur do-it-yourselfers should avoid direct contact with cement for any prolonged amount of time. Watertight boots, gloves, and clothing will prevent contact, and any accidental splash on exposed skin should be immediately washed away. Education and awareness of the consequences of cement burns are the best prevention.

GENERAL PURPOSE

To review the management of a patient with a chemical burn from wet cement.

TARGET AUDIENCE

This continuing education activity is intended for physicians, physician assistants, nurse practitioners, and registered nurses with an interest in skin and wound care.

LEARNING OBJECTIVES/OUTCOMES

After participating in this educational activity, the participant will:

1. Recognize the clinical presentation of a patient with a chemical burn from contact with wet cement.

2. Describe features related to the pathophysiology of alkali burns from wet cement.

3. Select the proper decontamination procedure after exposure to wet cement.

4. Identify steps in the treatment of a patient with a chemical burn from contact with wet cement.
Operative Management of Y-Shaped Metatarsal with Biphalangeal Sixth Toe
Authors: Montaño-Jiménez Pedro , Pérez-Belloso Ana Juana , Muriel-Sánchez Juan Manuel , Márquez-Reina Salvador , Goméz-Carrión Alvaro , Coheña-Jiménez Manuel
Published: June 2024

Background

In the literature, there is no consensus regarding the surgical management of postaxial polydactyly, and few cases of polymetatarsia with polydactyly have been reported. Treatment of the complete deformity will prevent further foot and gait disorders.

Objective

To identify literature relevant to the operative management of Y-shaped metatarsal with biphalangeal sixth toe and related skin and wound care to improve surgical treatment protocols from a clinical experience perspective.

Data Sources

The authors searched several electronic databases in December 2022 for articles related to postaxial polysyndactyly in the feet and polymetatarsia. Databases searched included PubMed, SciELO, ScienceDirect, Cochrane Database of Systematic Reviews, and Google Scholar gray literature.

Study Selection

Two independent researchers conducted the searches and read the article titles and abstracts. Studies were included if they were narrative reviews, case studies, or observational studies; written in English or Spanish; and published between 2012 and 2022. Nonhuman studies were excluded. Studies that met the inclusion criteria were fully evaluated. Disagreements between reviewers were resolved by consensus, and when there was no consensus, a senior researcher was consulted.

Data Extraction

The following data were extracted from the included studies using a standardized form: author and year of publication, study type, number of participants, sex, polydactyly location, polymetatarsia, type of polydactyly, participants’ history of hereditary associated diseases or malformations, treatment, removal criteria, and timing of surgery.

Data Synthesis

Authors evaluated 11 studies of postaxial polydactyly that included a total of 153 participants (64 men, 89 women). They also document their clinical experience with a surgical technique used in cases of bilateral postaxial polydactyly of the foot with a Y-shaped metatarsal with biphalangeal sixth toe.

Conclusions

Surgical correction with lateral removal of the sixth toe is a resolutive treatment to improve the functionality of the foot, its aesthetic appearance, and the patient’s quality of life. Case-specific treatment should be applied and tailored to meet the individual needs. The biomechanics of gait and shoe problems in these patients improve with surgical treatment, without presenting secondary aesthetic problems in skin care.
The Knowledge, Attitudes, and Practices of Parents Regarding Sun Protection for Their Children
Authors: Akca Gulfer , Akca Unal , Sahin Mustafa Kursat
Published: June 2024

Objective

To evaluate the knowledge, attitudes, and practices of parents toward protecting their children against skin cancer and the sun.

Methods

This cross-sectional study was performed in Turkey from March through October 2022. The authors used a questionnaire investigating the parents’ and children’s characteristics, attitudes, and practices toward sun protection and the Skin Cancer and Sun Knowledge (SCSK) scale to collect data.

Results

Of 465 parents, 60.2% were women, 83.2% were light-skinned, 20.2% perceived their children as risk-free, 43.8% perceived their children as low risk in terms of skin cancer, 14.6% examined their children from head to foot, 62.3% applied sunscreen to their children, 9.7% made them wear long-sleeved clothing, 60.0% made them wear headgear, 61.1% made them remain in the shade or under a sunshade, and 32.3% made them wear sunglasses. The mean parental SCSK scale score was 14.3 ± 4.1. Scale scores were higher among those who perceived their children as being at high risk for skin cancer (P = .000), whose children had not experienced red or painful sunburn in the previous year (P = .000), and who informed their children about sun protection (P = .000).

Conclusions

Although knowledge of skin cancer and solar protection was high, parental perception of the risk of skin cancer was very low, and attitudes toward skin examination were also very relaxed.
The Experiences of People Who Smoke With Type 2 Diabetes
Authors: Noonan Devon , Jackson Jennifer , Ghazaleh Haya Abu , Mcdermott Mairtin S. , Sang Elaine , Duaso Maria J.
Published: June 2024

Few interventions to support smoking cessation include content specifically about diabetes. This is problematic, as people with diabetes face unique challenges when they stop smoking. The purpose of this study was to understand patients' needs and challenges in relation to smoking with Type 2 diabetes and assess the acceptability of a text message intervention to support smoking cessation. People who smoke and have Type 2 diabetes in the United States and the United Kingdom were recruited to participate in semistructured interviews (n = 20), guided by the Capability, Opportunity, Motivation, and Behavior model. A combination of inductive and deductive approaches with framework analysis was used to analyze the data. Results indicated that the participants' experiences related to the constructs of the Capability, Opportunity, Motivation, and Behavior model and the categories of mental health and diabetes distress were also notable parts of their experiences. Results can be used to guide intervention development in this unique group.
Understanding Nurse Perceptions of Caring for Patients With Alcohol Use Disorder
Authors: Hyde Ashley , Johnson Emily , Bray Christina , Meier Tiara , Carbonneau Michelle , Spiers Jude , Tandon Puneeta
Published: June 2024

Background

Alcohol use disorder (AUD), the problematic consumption of alcohol, affects 107 million people worldwide. Individuals with AUD experience high morbidity and increased mortality. Nurses practicing in acute care are ideally positioned to deliver quality interventions to patients with AUD, including screening and brief intervention; formal training and assessment of baseline knowledge, attitudes, and perceptions are necessary.

Aims and Objectives

The aim of this study was to explore the knowledge, attitudes, and perceptions of acute care nurses caring for patients with AUD.

Design

This study used a cross-sectional survey design.

Methods

The Survey of Attitudes and Perceptions was completed by 93 nurses working in six acute care centers (seven medicine units) across Alberta. Data were analyzed using descriptive and inferential statistics.

Results

Few participants reported receiving any prior structured training on AUD, with the majority reporting limited knowledge of alcohol and the effects of alcohol consumption. Although most participants said that caring for patients with AUD was a part of their professional role, few felt satisfied or motivated to work with this group of patients. Responses to individual questions or subdomains of the survey did not significantly differ by length of time in professional role, employment status, or sex.

Conclusion

Our results indicate that nurses need to learn more about caring for patients with AUD. Developing tailored educational interventions that are mindful of the importance of knowledge, support, satisfaction, and motivation is necessary to improve the quality of care for patients with AUD.
Effect of an Online Intervention on Nursing Students' Alcohol Consumption and Social Support
Authors: Gonçalves Jamila Souza , Oliveira Jaqueline Lemos de , Almeida Janaína Cristina Pasquini de , Morero Juceli Andrade Paiva , Pegoraro Natália Priolli Jora , Zanetti Maria Olívia Barboza , Souza Jacqueline de
Published: June 2024

Objective

This research aimed to evaluate the impact of custom-developed software on nursing students' alcohol consumption and perception of social support.

Method

A quasi-experimental study was conducted with 88 students in the early years of nursing courses at a Brazilian public university. The members of the intervention group (n = 40) participated in a lecture delivered by a nurse and used online software developed based on cognitive behavioral techniques and social skills training. The members of the control group (n = 48) participated only in the lecture. Data on alcohol consumption profiles and social support characteristics were collected. Descriptive statistics, an analysis of variance test, and the Dunnett's test were utilized for data analysis.

Results

Alcohol consumption decreased in both groups without significant differences between them. However, in terms of frequency of use, binge drinking, and the number of drinks consumed, a significant decrease occurred among participants in the intervention group. Regarding social support, both groups showed an increase in satisfaction with support and a decrease in the number of supporters. This reduction was less pronounced in the intervention group than in the control group.

Conclusion

This investigation presents relevant results that suggest the potential of using online technologies as supplemental materials for promoting students' mental health.
ArtSpective™ for Perinatal Substance Use
Authors: Shuman Clayton J. , Choberka David , Morgan Mikayla E. , Boyd Carol J.
Published: June 2024

Objective

The purpose of this proof-of-concept pilot study was to test the initial feasibility and limited efficacy of ArtSpective™ for perinatal substance use (PSU), a novel, arts-based intervention designed to decrease stigmatizing attitudes toward PSU.

Methods

Using a pre–post mixed methods quasi-experimental design, ArtSpective™ for PSU was pilot tested for proof of concept among a convenience sample of 11 undergraduate and graduate students with experience in maternal–infant nursing from a Midwestern U.S. nursing school. As a proof-of-concept pilot study, we evaluated feasibility (acceptability, demand, and implementation) and limited efficacy. Participants completed presurveys and postsurveys that included satisfaction items, demographic items, and an adapted version of the Attitudes About Drug Use in Pregnancy Scale and participated in a focus group. Focus group data were analyzed using constant comparative methods, and survey data were analyzed using descriptive statistics and Wilcoxon signed rank tests.

Results

Participants reported high demand and satisfaction with the intervention and provided recommendations to improve scalability. ArtSpective™ demonstrated significant improvement in stigma toward PSU (pre vs. post: p = .003; d = .633).

Conclusion

ArtSpective™ for PSU demonstrated initial feasibility and limited efficacy for improving nurse attitudes toward PSU. Efforts are needed to further test this novel intervention, adapt it to augment existing educational interventions, and improve its scalability.
Systemic autoimmune disease patients’ blood immunome reveals specificities and commonalities among different diagnostic entities
Authors: Rybakowska Paulina , Van Gassen Sofie , Barturen Guillermo , Sánchez Carlos Pérez , Ibáñez-Costa Alejandro , Varela Nieves , Castro Rafaela Ortega , Fernández-Roldán Concepción , Jiménez-Moleón Inmaculada , Ortego Norberto , Raya Enrique , Quesada Rocío Aguilar , López-Pedrera Chary , Collantes Eduardo , Saeys Yvan , Marañón Concepción , Alarcón-Riquelme Marta E.
Published: June 2024

1

Background

Systemic autoimmune diseases (SADs) are characterized by internal heterogeneity, overlapping clinical symptoms, and shared molecular pathways. Therefore, they are difficult to diagnose and new tools allowing precise diagnosis are needed. Molecular-based reclassification studies enable to find patterns in a diagnosis-independent way.

Objective

To evaluate the possibility of using high-content immunophenotyping for detecting patient subgroups in the context of precise treatment.

Methods

Whole blood high-content immunophenotyping of 101 patients with 7 systemic autoimmune diseases and 22 controls was performed using 36-plex mass cytometry panel. Patients were compared across diagnostic entities and re-classified using Monte Carlo reference-based consensus clustering. Levels of 45-plex multiplexed cytokine were measured and used for cluster characterization.

Results

Differential analysis by diagnosis did not reveal any disease-specific pattern in the cellular compositions and phenotypes but rather their relative similarities. Accordingly, patients were classified into phenotypically distinct groups composed of different diagnostic entities sharing common immunophenotypes and cytokine signatures. These features were mainly based on granulocyte activation and CD38 expression in discrete lymphocyte populations and were related to Th17 or IFN-dependent cytokines.

Conclusions

Our data indicate that specific individuals could potentially benefit from the same line of treatment independently of their diagnosis and emphasize the possibility of using immunophenotyping as a stratification tool in precision rheumatology.

2

Graphical abstract

Key messages

Whole blood immmunophenotyping could be used to stratify systemic autoimmune patients, thus it is a useful tool in precision medicine.

Patients’ groups could benefit from the same line of treatment.
Towards a universal spatial molecular atlas of the mouse brain
Authors: He Yichun , Sheng Hao , Shi Hailing , Wang Wendy Xueyi , Tang Zefang , Liu Jia , Wang Xiao
Published: June 2024

Spatially mapping a comprehensive brain at the single-cell level with molecular resolution is crucial for understanding its biological structure, mechanisms, and functions. Recent scalable spatial transcriptomics technologies have revolutionized our ability to examine millions of cells within the complex brain network, allowing for the generation of multiple mouse brain atlases that illuminate diverse transcriptomic and spatial cell types. However, despite enormous efforts, these spatial transcriptomics atlases still face challenges in providing a comprehensive brain representation: each atlas only captures a fraction of the vast cellular population of the brain and is limited in one or more aspects of spatial resolution, gene detection sensitivity, and gene throughput. Here, we introduce FuseMap, a deep-learning-based framework for spatial transcriptomics that bridges single-cell or single-spot gene expression with spatial contexts and consolidates various gene panels across spatial transcriptomics atlases. By training on an extensive spatial transcriptomics atlas corpus of the mouse brain, comprising over 18.6 million cells or spots and 26,665 genes from 434 tissue sections across seven datasets in a self-supervised way, FuseMap gains a fundamental understanding of cell identities and gene characteristics. We thus create a comprehensive molecular spatial reference atlas of the whole mouse brain with transcriptome-wide information, achieving multiple tasks including nomenclature harmonization of molecular cell types and tissue regions, identification of novel molecular brain regions, spatial gene imputation, targeted gene-panel selection, and region-specific cell-type interactions inference. Furthermore, the pretrained brain FuseMap model enables mapping new query data to the molecular spatial reference brain through transfer learning, allowing for automated cell and tissue annotations and replacing laborious and suboptimal manual annotations. Overall, we offer FuseMap as a novel computational framework for integration across various spatial transcriptomics platforms and provide a molecular common coordinate framework (molCCF) with pretrained FuseMap brain model for exploration of the brain molecular and cellular landscape with harmonized annotations and coordinates.
Ex vivoSIM-AFM measurements reveal the spatial correlation of stiffness and molecular distributions in 3D living tissue
Authors: Shioka Itsuki , Morita Ritsuko , Yagasaki Rei , Wuergezhen Duligengaowa , Yamashita Tadahiro , Fujiwara Hironobu , Okuda Satoru
Published: June 2024

Living tissues each exhibit a distinct stiffness, which provides cells with key environmental cues that regulate their behaviors. Despite this significance, our understanding of the spatiotemporal dynamics and the biological roles of stiffness in three-dimensional tissues is currently limited due to a lack of appropriate measurement techniques. To address this issue, we propose a new method combining upright structured illumination microscopy (USIM) and atomic force microscopy (AFM) to obtain precisely coordinated stiffness maps and biomolecular fluorescence images of thick living tissue slices. Using mouse embryonic skin as a representative tissue with mechanically heterogeneous structures inside, we validate the measurement principle of USIM-AFM. Live measurement of tissue stiffness distributions revealed the highly heterogeneous mechanical nature of embryonic skin as well as the role of collagens in maintaining its integrity. Furthermore, quantitative comparisons of stiffness distributions of preserved tissue samples unveiled the distinct impacts of conventional tissue preservation techniques on the tissue stiffness pattern. This series of experiments highlights the importance of live mechanical testing of tissue-scale samples. Our USIM-AFM technique provides a new methodology to reveal the dynamic nature of tissue stiffness and its correlation with biomolecular distributions in live tissues and thus could serve as a technical basis for exploring tissue-scale mechanobiology.

Graphical Abstract
Brain representation in conscious and unconscious vision
Authors: Mei Ning , Soto David
Published: June 2024

The development of robust frameworks to understand how the human brain represents conscious and unconscious perceptual contents is paramount to make progress in the neuroscience of consciousness. Recent functional MRI studies using multi-voxel pattern classification analyses showed that unconscious contents could be decoded from brain activity patterns. However, decoding does not imply a full understanding of neural representations. Here we re-analysed data from a high-precision fMRI study coupled with representational similarity analysis based on convolutional neural network models to provide a detailed information-based approach to neural representations of both unconscious and conscious perceptual content. The results showed that computer vision model representations strongly predicted brain responses in ventral visual cortex and in fronto-parietal regions to both conscious and unconscious contents. Moreover, this pattern of results generalised when the models were trained and tested with different participants. Remarkably, these observations results held even when the analysis was restricted to observers that showed null perceptual sensitivity. In light of the highly distributed brain representation of unconscious information, we suggest that the functional role of fronto-parietal cortex in conscious perception is unlikely to be related to the broadcasting of information, as proposed by the global neuronal workspace theory, and may instead relate to the generation of meta-representations as proposed by higher-order theories.
Caffeine induces age-dependent increases in brain complexity and criticality during sleep
Authors: Thölke Philipp , Arcand-Lavigne Maxine , Lajnef Tarek , Frenette Sonia , Carrier Julie , Jerbi Karim
Published: June 2024

Caffeine is the most widely consumed psychoactive stimulant worldwide. Yet important gaps persist in understanding its effects on the brain, especially during sleep. We analyzed sleep EEG in 40 subjects, contrasting 200mg of caffeine against a placebo condition, utilizing inferential statistics and machine learning. We found that caffeine ingestion led to an increase in brain complexity, a widespread flattening of the power spectrum's 1/f-like slope, and a reduction in long-range temporal correlations. Being most prominent during non-REM sleep, these results suggest that caffeine shifts the brain towards a critical regime and more diverse neural dynamics. Interestingly, this was more pronounced in younger adults (20-27 years) compared to middle-aged participants (41-58 years) whose sleep brain dynamics were less affected by caffeine. Interpreting these data in the light of modeling and empirical work on EEG-derived measures of excitation-inhibition balance provides novel insights into the effects caffeine has on the sleeping brain.
Oxygen Sensor-Guided Fine Needle Biopsy Studies of Human Cancer Xenografts in Mice
Authors: McDonald Robert C. , Fischer Andrew H. , Rusckowski Mary
Published: June 2024

An oxygen sensor-mounted fine-needle biopsy tool was used forin vivomeasurement of oxygen levels in tumor xenografts. The system provides a means of measuring the oxygen content in harvested tumor tissue from specific locations. Oxygen in human tumor xenografts in a murine model was observed for over 1 min. Tissues were mapped in relation to oxygen tension (pO2) readings and sampled for conventional cytological examination. Careful modeling of the pO2readings over 60 seconds yielded a diffusion coefficient for oxygen at the sensor tip, providing additional diagnostic information about the tissue before sampling. Oxygen level measurement may provide a useful adjunct to the use of biomarkers in tumor diagnosis.
Injury distance limits the transcriptional response to spinal injury
Authors: Wang Zimei , Kumaran Manojkumar , Batsel Elizabeth , Testor-Cabrera Sofia , Beine Zac , Ribelles Alicia Alvarez , Tsoulfas Pantelis , Venkatesh Ishwariya , Blackmore Murray G.
Published: June 2024

The ability of neurons to sense and respond to damage is fundamental to homeostasis and nervous system repair. For some cell types, notably dorsal root ganglia (DRG) and retinal ganglion cells (RGCs), extensive profiling has revealed a large transcriptional response to axon injury that determines survival and regenerative outcomes. In contrast, the injury response of most supraspinal cell types, whose limited regeneration constrains recovery from spinal injury, is mostly unknown. Here we employed single-nuclei sequencing in mice to profile the transcriptional responses of diverse supraspinal cell types to spinal injury. Surprisingly, thoracic spinal injury triggered only modest changes in gene expression across all populations, including corticospinal tract (CST) neurons. Moreover, CST neurons also responded minimally to cervical injury but much more strongly to intracortical axotomy, including upregulation of numerous regeneration and apoptosis-related transcripts shared with injured DRG and RGC neurons. Thus, the muted response of CST neuron to spinal injury is linked to the injury’s distal location, rather than intrinsic cellular characteristics. More broadly, these findings indicate that a central challenge for enhancing regeneration after a spinal injury is the limited sensing of distant injuries and the subsequent modest baseline neuronal response.
CD4+tumor-infiltrating lymphocytes secreting T cell-engagers induce regression of autologous patient-derived non-small cell lung cancer xenografts
Authors: Jiménez-Reinoso Anaïs , Molero-Abraham Magdalena , Cirauqui Cristina , Blanco Belén , Garrido-Martin Eva M. , Nehme-Álvarez Daniel , Domínguez-Alonso Carmen , Ramírez-Fernández Ángel , Díez-Alonso Laura , Nuñez-Buiza Ángel , González-Murillo África , Tobes Raquel , Pareja Eduardo , Ramírez-Orellana Manuel , Rodriguez-Peralto José L. , Ferrer Irene , Zugazagoitia Jon , Paz-Ares Luis , Álvarez-Vallina Luis
Published: June 2024

Adoptive transfer of tumor-infiltrating lymphocytes (TIL) has shown remarkable results in melanoma, but only modest clinical benefit in other cancers, even after TIL have been genetically modified to improve their tumor homing, cytotoxic potential or overcoming cell exhaustion. The requiredex vivoTIL expansion process may induce changes in the T cell clonal composition, which could likely compromise the tumor reactivity of TIL preparations and ultimately the success of TIL therapy. A promising approach based on the production of bispecific T cell engagers (TCE) by engineered T cells (STAb-T therapy) improves the efficacy of current T cell redirection strategies against tumor-associated antigens in hematological tumors. We studied the TCRβ repertoire in non-small cell lung cancer (NSCLC) tumors and inex vivoexpanded TIL from two unrelated patients. We generated TIL secreting anti-epidermal growth factor receptor (EGFR) x anti-CD3 TCE (TILSTAb) and tested their antitumor efficacyin vitroandin vivousing a NSCLC patient-derived xenograft (PDX) model in which tumor fragments and TIL from the same patient were transplanted intohIL-2NOG mice. We confirmed that the standard TIL expansion protocol promotes the loss of tumor-dominant T cell clones and the overgrowth of virus-reactive TCR clonotypes that were marginally detectable in primary tumors. We demonstrated the antitumor activity of TILSTAbbothin vitroandin vivowhen administered intratumorally and systemically in an autologous immune-humanized PDX EGFR+NSCLC mouse model, where tumor regression was mediated by TCE-redirected CD4+TIL bearing non-tumor dominant clonotypes.

SIGNIFICANCE

Epithelial tumor-derived TIL can be engineered to secrete TCE capable of redirecting T cells bearing non-tumor-dominant clonotypes regardless of their phenotype, which could have broad applications in immunotherapy for solid tumors.
CTCF regulates global chromatin accessibility and transcription during rod photoreceptor development
Authors: Chen Dahong , Keremane Saumya , Wang Silu , Lei Elissa P.
Published: June 2024

Chromatin architecture facilitates accurate transcription at a number of loci, but it remains unclear how much chromatin architecture is involved in global transcriptional regulation. Previous work has shown that rapid depletion of the architectural protein CTCF in cell culture strongly alters chromatin organization but results in surprisingly limited gene expression changes. This discrepancy has also been observed when other architectural proteins are depleted, and one possible explanation is that full transcriptional changes are masked by cellular heterogeneity. We tested this idea by performing multi-omics analyses with sorted post-mitotic mouse rods, which undergo synchronized development, and identified CTCF-dependent regulation of global chromatin accessibility and gene expression. Depletion of CTCF leads to dysregulation of ∼20% of the entire transcriptome (>3,000 genes) and ∼41% of genome accessibility (>26,000 sites), and these regions are strongly enriched in euchromatin. Importantly, these changes are highly enriched for CTCF occupancy, suggesting direct CTCF binding and transcriptional regulation at these active loci. CTCF mainly promotes chromatin accessibility of these direct binding targets, and a large fraction of these sites correspond to promoters. At these sites, CTCF binding frequently promotes accessibility and inhibits expression, and motifs of transcription repressors are found to be significantly enriched. Our findings provide different and often opposite conclusions from previous studies, emphasizing the need to consider cell heterogeneity and cell type specificity when performing multi-omics analyses. We conclude that the architectural protein CTCF binds chromatin and regulates global chromatin accessibility and transcription during rod development.
Accurate, scalable, and fully automated inference of species trees from raw genome assemblies using ROADIES
Authors: Gupta Anshu , Mirarab Siavash , Turakhia Yatish
Published: June 2024

Inference of species trees plays a crucial role in advancing our understanding of evolutionary relationships and has immense significance for diverse biological and medical applications. Extensive genome sequencing efforts are currently in progress across a broad spectrum of life forms, holding the potential to unravel the intricate branching patterns within the tree of life. However, estimating species trees starting from raw genome sequences is quite challenging, and the current cutting-edge methodologies require a series of error-prone steps that are neither entirely automated nor standardized. In this paper, we present ROADIES, a novel pipeline for species tree inference from raw genome assemblies that is fully automated, easy to use, scalable, free from reference bias, and provides flexibility to adjust the tradeoff between accuracy and runtime. The ROADIES pipeline eliminates the need to align whole genomes, choose a single reference species, or pre-select loci such as functional genes found using cumbersome annotation steps. Moreover, it leverages recent advances in phylogenetic inference to allow multi-copy genes, eliminating the need to detect orthology. Using the genomic datasets released from large-scale sequencing consortia across three diverse life forms (placental mammals, pomace flies, and birds), we show that ROADIES infers species trees that are comparable in quality with the state-of-the-art approaches but in a fraction of the time. By incorporating optimal approaches and automating all steps from assembled genomes to species and gene trees, ROADIES is poised to improve the accuracy, scalability, and reproducibility of phylogenomic analyses.

Code and Data availability

The source code of ROADIES is freely available under the MIT License on GitHub (https://github.com/TurakhiaLab/ROADIES), and the documentation for ROADIES is available athttps://turakhia.ucsd.edu/ROADIES/. The details of the input datasets used in the manuscript are listed in Supplementary Tables 1-3. All inferred gene trees and species trees are to be deposited to Dryad with links to be made available on the aforementioned GitHub repository.

Contact

yturakhia@ucsd.edu
Interference underlies attenuation upon relearning in sensorimotor adaptation
Authors: Avraham Guy , Ivry Richard B
Published: June 2024

Savings refers to the gain in performance upon relearning a task. In sensorimotor adaptation, savings is tested by having participants adapt to perturbed feedback and, following a washout block during which the system resets to baseline, presenting the same perturbation again. While savings has been observed with these tasks, we have shown that the contribution from implicit sensorimotor adaptation, a process that uses sensory prediction errors to recalibrate the sensorimotor map, is actually attenuated upon relearning (Avraham et al., 2021). In the present study, we test the hypothesis that this attenuation is due to interference arising from the washout block, and more generally, from experience with a different relationship between the movement and the feedback. In standard adaptation studies, removing the perturbation at the start of the washout block results in a salient error signal in the opposite direction to that observed during learning. As a starting point, we replicated the finding that implicit adaptation is attenuated following a washout period in which the feedback now signals a salient opposite error. When we eliminated visual feedback during washout, implicit adaptation was no longer attenuated upon relearning, consistent with the interference hypothesis. Next, we eliminated the salient error during washout by gradually decreasing the perturbation, creating a scenario in which the perceived errors fell within the range associated with motor noise. Nonetheless, attenuation was still prominent. Inspired by this observation, we tested participants with an extended experience with veridical feedback during an initial baseline phase and found that this was sufficient to cause robust attenuation of implicit adaptation during the first exposure to the perturbation. This effect was context-specific: It did not generalize to movements that were not associated with the interfering feedback. Taken together, these results show that the implicit sensorimotor adaptation system is highly sensitive to memory interference from a recent experience with a discrepant action-outcome contingency.