bluuebunny/crossref_metadata_2025 huggingface dataset:
Stromal STAT5-Mediated Trophic Activity Regulates Hematopoietic Niche Factors
Authors: Wang Zhengqi , Emmel Grace , Lim Hong Seo , Zhu Wandi , Kosters Astrid , Ghosn Eliver E B , Qiu Peng , Bunting Kevin D
Published: July 2023

Signal transducer and activator of transcription 5 (STAT5a and STAT5b) are intrinsically critical for normal hematopoiesis but are also expressed in stromal cells. Here, STAT5ab knockout (KO) was generated with a variety of bone marrow hematopoietic and stromal Cre transgenic mouse strains. Vav1-Cre/+STAT5abfl/fl, the positive control for loss of multipotent hematopoietic function, surprisingly dysregulated niche factor mRNA expression, and deleted STAT5ab in CD45neg cells. Single-cell transcriptome analysis of bone marrow from Vav1-Cre/+ wild-type or Vav1-Cre/+STAT5abfl/fl mice showed hematopoietic stem cell (HSC) myeloid commitment priming. Nes+ cells were detected in both CD45neg and CD45+ clusters and deletion of STAT5ab with Nes-Cre caused hematopoietic repopulating defects. To follow up on these promiscuous Cre promoter deletions in CD45neg and CD45+ bone marrow cell populations, more stroma-specific Cre strains were generated and demonstrated a reduction in multipotent hematopoietic progenitors. Functional support for niche-supporting activity was assessed using STAT5-deficient mesenchymal stem cells (MSCs). With Lepr-Cre/+STAT5abfl/fl, niche factor mRNAs were downregulated with validation of reduced IGF-1 and CXCL12 proteins. Furthermore, advanced computational analyses revealed a key role for STAT5ab/Cish balance with Cish strongly co-expressed in MSCs and HSCs primed for differentiation. Therefore, STAT5ab-associated gene regulation supports the bone marrow microenvironment.
Microbiotoxicity: antibiotic usage and its unintended harm to the microbiome
Authors: Theodosiou Anastasia A. , Jones Christine E. , Read Robert C. , Bogaert Debby
Published: July 2023

Purpose of review

Antibiotic use is associated with development of antimicrobial resistance and dysregulation of the microbiome (the overall host microbial community). These changes have in turn been associated with downstream adverse health outcomes. This review analyses recent important publications in a rapidly evolving field, contextualizing the available evidence to assist clinicians weighing the potential risks of antibiotics on a patient's microbiome.

Recent finding

Although the majority of microbiome research is observational, we highlight recent interventional studies probing the associations between antibiotic use, microbiome disruption, and ill-health. These studies include germ-free mouse models, antibiotic challenge in healthy human volunteers, and a phase III study of the world's first approved microbiome-based medicine.

The growing body of relevant clinical and experimental evidence for antibiotic-mediated microbiome perturbation is concerning, although further causal evidence is required. Within the limits of this evidence, we propose the novel term ‘microbiotoxicity’ to describe the unintended harms of antibiotics on a patient's microbiome. We suggest a framework for prescribers to weigh microbiotoxic effects against the intended benefits of antibiotic use.
Keep numbers in view: red-eared sliders (
Trachemys scripta elegans
) learn to discriminate relative quantities
Authors: Sun Xiaoqian , Piao Yige , Wang Tongliang , Wang Jichao , Fu Jinzhong , Cui Jianguo
Published: July 2023

The ability to discriminate relative quantities, one of the numerical competences, is considered an adaptive trait in uncertain environments. Besides humans, previous studies have reported this capacity in several non-human primates and birds. Here, we test whether red-eared sliders (
Trachemys scripta elegans
) can discriminate different relative quantities. Subjects were first trained to distinguish different stimuli with food reward. Then, they were tested with novel stimulus pairs to demonstrate how they distinguished the stimuli. The results show that most subjects can complete the initial training and use relative quantity rather than absolute quantity to make choices during the testing phase. This study provides behavioural evidence of relative quantity discrimination in a reptile species and suggests that such capacity may be widespread among vertebrates.
Small bots, big impact: solving the conundrum of cooperation in optional Prisoner’s Dilemma game through simple strategies
Authors: Sharma Gopal , Guo Hao , Shen Chen , Tanimoto Jun
Published: July 2023

Cooperation plays a crucial role in both nature and human society, and the conundrum of cooperation attracts the attention from interdisciplinary research. In this study, we investigated the evolution of cooperation in optional Prisoner’s Dilemma games by introducing simple bots. We focused on one-shot and anonymous games, where the bots could be programmed to always cooperate, always defect, never participate or choose each action with equal probability. Our results show that cooperative bots facilitate the emergence of cooperation among ordinary players in both well-mixed populations and a regular lattice under weak imitation scenarios. Introducing loner bots has no impact on the emergence of cooperation in well-mixed populations, but it facilitates the dominance of cooperation in regular lattices under strong imitation scenarios. However, too many loner bots on a regular lattice inhibit the spread of cooperation and can eventually result in a breakdown of cooperation. Our findings emphasize the significance of bot design in promoting cooperation and offer useful insights for encouraging cooperation in real-world scenarios.
Nucleus accumbens core single cell ensembles bidirectionally respond to experienced versus observed aversive events
Authors: Dinckol Oyku , Zachry Jennifer E. , Kutlu Munir Gunes
Published: July 2023

Empathy is the ability to adopt others’ sensory and emotional states and is an evolutionarily conserved trait among mammals. In rodents, empathy manifests itself as social modulation of aversive stimuli such as acknowledging and acting on conspecifics’ distress. The neuronal network underlying social transmission of information is known to overlap with the brain regions that mediate behavioral responses to aversive and rewarding stimuli. In this study, we recorded single cell activity patterns of nucleus accumbens (NAc) core neurons using in vivo optical imaging of calcium transients via miniature scopes. This cutting-edge imaging methodology not only allows us to record activity patterns of individual neurons but also lets us longitudinally follow these individual neurons across time and different behavioral states. Using this approach, we identified NAc core single cell ensembles that respond to experienced and/or observed aversive stimuli. Our results showed that experienced and observed aversive stimuli evoke NAc core ensemble activity that is largely positive, with a smaller subset of negative responses. The size of the NAc single cell ensemble response was greater for experienced aversive stimuli compared to observed aversive events. Our results also revealed a subpopulation within the NAc core single cell ensembles that show a bidirectional response to experienced aversive stimuli versus observed aversive stimuli (i.e., negative response to experienced and positive response to observed). These results suggest that the NAc plays a role in differentiating somatosensory experience from social observation of aversion at a single cell level. This has important implications for psychopathologies where social information processing is maladaptive, such as autism spectrum disorders.
Genetically perturbed myelin as a risk factor for neuroinflammation-driven axon degeneration
Authors: Groh Janos , Abdelwahab Tassnim , Kattimani Yogita , Hörner Michaela , Loserth Silke , Gudi Viktoria , Adalbert Robert , Imdahl Fabian , Saliba Antoine-Emmanuel , Coleman Michael , Stangel Martin , Simons Mikael , Martini Rudolf
Published: July 2023

Axon degeneration and functional decline in myelin diseases are often attributed to loss of myelin but their relation is not fully understood. Perturbed myelinating glia can instigate chronic neuroinflammation and contribute to demyelination and axonal damage. Here we study mice with distinct defects in the proteolipid protein 1 gene that develop axonal damage which is driven by cytotoxic T cells targeting myelinating oligodendrocytes. We show that persistent ensheathment with perturbed myelin poses a risk for axon degeneration, neuron loss, and behavioral decline. We demonstrate that CD8+T cell-driven axonal damage is less likely to progress towards degeneration when axons are efficiently demyelinated by activated microglia. Mechanistically, we show that cytotoxic T cell effector molecules induce cytoskeletal alterations within myelinating glia and aberrant actomyosin constriction of axons at paranodal domains. Our study identifies detrimental axon-glia-immune interactions which promote neurodegeneration and possible therapeutic targets for disorders associated with myelin defects and neuroinflammation.
Cardiomyocyte mechanical memory is regulated through the talin interactome and DLC1 dependent regulation of RhoA
Authors: Marhuenda Emilie , Xanthis Ioannis , Pandey Pragati , Azad Amar , Richter Megan , Pavolvic Davor , Gehmlich Katja , Faggian Giuseppe , Ehler Elisabeth , Levitt James , Ameer-Beg Simon , Iskratsch Thomas
Published: July 2023

Mechanical properties are cues for many biological processes in health or disease. Likewise, in the heart it is becoming clearer that mechanical signals are critically involved in the disease progression. Cardiomyocytes sense the mechanical properties of their environment at costameres through integrins and associated proteins, including the mechanosensitive protein talin as an integral component. Our previous work indicated different modes of talin tension, depending on the extracellular matrix stiffness. Here, we wanted to study how this leads to downstream mechanotransduction changes, further influencing the cardiomyocyte phenotype. Combining immunoprecipitations and Fluorescence Recovery after Photobleaching (FRAP) experiments, we identify that the talin interacting proteins DLC1, RIAM and paxillin each preferentially bind to talin at specific extracellular matrix stiffness and this interaction is preserved even in absence of tension. This demonstrates a mechanical memory, which we confirm furtherin vivoin mouse hearts. The mechanical memory is regulated through adhesion related kinase pathways. Optogenetic experiments using the LOVTRAP systems confirm direct competition between the individual proteins, which again is altered through phosphorylation. DLC1 regulates RhoA activity in a stiffness dependent way and both loss and overexpression of DLC1 results in myofibrillar disarray. Together the study demonstrates a mechanism of imprinting mechanical information into the talin-interactome to finetune RhoA activity, with impacts on cardiac health and disease.
A Phase Separation-Fortified Bi-Specific Adaptor for Conditional Tumor Killing
Authors: Liu Yuyan , Zhu Yuting , Xu Weifan , Li Pilong
Published: July 2023

A common approach in the development of therapeutic proteins is the use of synthetic ligands with multivalency, allowing for sophisticated control of signal transduction. Leveraging the emerging concept of liquid-liquid phase separation (LLPS) and its ability to organize cell surface receptors into functional compartments, we herein have designed modular ligands with phase-separation modalities to engineer programmable interreceptor communications and precise control of signal pathways, thus inducing the rapid, potent, and specific apoptosis of tumor cells. Despite their simplicity, these “triggers”, named phase-separated Tumor Killers (hereafter referred to as psTK), are sufficient to yield interreceptor clustering of death receptors (represented by DR5) and tumor-associated receptors, with the following features: LLPS-mediated robust high-order organization, well-choreographed conditional activation, and broad-spectrum capacity for potently inducing apoptosis of tumor cells. The development of novel therapeutic proteins with phase-separation modalities showcases the power of spatially reorganizing signal transduction. This approach enables the branching of cell fate and holds promising potential for targeted therapies against challenging tumors.

One-Sentence Summary

Engineered modular ligands with phase-separation modalities can drive lethal dialog with tumor cells.
CARs are organized in nanodomains in the plasma membrane of T cells that accumulate at tumor contact sites
Authors: Verbruggen Christina , Gehrke Leon , Banholzer Nicole , Ghosh Arindam , Reinhard Sebastian , Weber Justus , Doose Sören , Einsele Hermann , Hudecek Michael , Nerreter Thomas , Sauer Markus
Published: July 2023

Chimeric antigen receptors (CARs) are synthetic immune receptors that are expressed in T cells through genetic engineering. CAR-T cells have been successfully used to eradicate very advanced leukemias and lymphomas and their functional properties have been intensively studied. However, relatively little is known about the spatiotemporal expression and organization of CARs on the T-cell membrane and how this influences their efficacy. Here, we applied super-resolution microscopy to visualize CD19-, ROR1-, and ROR2-specific CARs in human CD4+and CD8+T cells that were engineered with lentiviral and transposon-mediated gene transfer. Our data show that the majority of CARs is organized in nanodomains virtually independent of the T cell type, CAR construct and expression level. Quantitative analyses revealed a slightly higher CAR density in transposon-engineered T cells correlating with higher antigen sensitivity and faster resolution of anti-tumor functions compared to lentivirally-engineered T cells. Live-cell fluorescence imaging revealed that both, CAR nanodomains and CAR monomers accumulate at tumor contact sites and form multifocal immunological synapses. Our study provides novel insights into the membrane organization of CARs with single-molecule resolution and illustrates the potential of advanced microscopy to inform the rational design of synthetic immune receptors for applications in immune cell therapy.
Southern multilateralism from IBSA to NDB: Synergies, continuities and regional options
Authors: Alden Chris , le Pere Garth
Published: July 2023

The shifting nature of contemporary global politics highlights the growing contestation about power and how it is distributed, with multipolarity as its hallmark and distinguishing feature. Amid the shift to multipolarity, new forms of multilateralism are emerging from the South, which are grounded in ‘institutional arrangements led by countries of the Global South’ in terms of the origin of initiatives, the drivers of such arrangements and the resources to sustain them. In this context, Southern Multilateralism offers a differ approach to classical Realist thinking where power is ‘the final arbiter of things political’. Southern Multilateralism has also given rise to new international institutional arrangements, such as the BRICS‐led New Development Bank (NDB) and its predecessor, the India, Brazil and South Africa (IBSA) Trilateral Forum and the IBSA Fund Facility for Poverty and Hunger Alleviation.

This article compares the IBSA and their Fund with the NDB and argues that there are continuities and linkages between the NDB and the IBSA Fund, which have yet to be examined by scholars; and to be more precise, the NDB has absorbed and reflects, key attributes of the IBSA and their Fund. Moreover, this study concludes by suggesting regional collaboration options for the NDB, led by South Africa, India and Brazil and their respective regions, whereby the NDB can expand its global role and relevance in future via its regional offices, particularly by supporting the regional trade integration plans in Africa, South Asia and South America.
Different effects of chronic omeprazole use on osteoporotic fractures rate in the elderly
Authors: Gingold‐Belfer Rachel , Beloosesky Yichayaou , Amara Amir , Sharon Eran , Boltin Doron , Koren‐Morag Nira , Meyerovitch Joseph , Schmilovitz‐Weiss Hemda
Published: July 2023

Aims

To investigate the potential association of chronic use of omeprazole with the occurrence of osteoporotic fractures (OF) in community‐dwelling elderly subjects.

Methods

The cohort consisted of community‐dwelling residents aged >65 years registered with a large health maintenance organization in Israel between January 2002 and December 2016. Data were retrospectively collected from the electronic medical files on demographics, parameters known to be associated with OF, diagnoses of osteoporotic hip, wrist, and vertebral fractures, and chronic use of omeprazole (>11 prescriptions/year). Time to OF/death/end of study was calculated from the beginning of the study (2002). The risk of fractures in the chronic users of omeprazole was analyzed by multivariate Cox proportional hazard regression model.

Results

In total, 46 805 subjects were included (41% men), mean age 83.4±6.4 years, of whom 10 272 (21.9%) were chronic users of omeprazole. During 14 years of follow‐up, OF were diagnosed in 414 (4.0%) omeprazole users and 1007 (2.8%) omeprazole nonusers (p < 0.001). In a Cox regression model adjusted for age and gender only, chronic use of omeprazole was associated with a 16% excess of OF. However, when parameters known to be associated with OF were entered into the multivariate Cox regression model, chronic use of omeprazole was not found to be an independent risk factor for OF, either overall (adjusted hazard ratio = 0.965, 95% confidence interval 0.86–1.08, P = .55) or specifically, in the ≥85 years age group (adjusted hazard ration = 0.780, 95% confidence interval 0.635–0.958, P < .05) in which an inverse correlation between omeprazole use and OF, was demonstrated.

Conclusions

Chronic use of omeprazole was not associated with the occurrence of OF in elders.
Patterns of pharmacotherapy for bipolar disorder: A GBC survey
Authors: Singh Balwinder , Yocum Anastasia K. , Strawbridge Rebecca , Burdick Katherine E. , Millett Caitlin E. , Peters Amy T. , Sperry Sarah H. , Fico Giovanna , Vieta Eduard , Verdolini Norma , Godin Ophelia , Leboyer Marion , Etain Bruno , Tso Ivy F. , Coombes Brandon J. , McInnis Melvin G. , Nierenberg Andrew A. , Young Allan H. , Ashton Melanie M. , Berk Michael , Williams Lana J. , Keramatian Kamyar , Yatham Lakshmi N. , Overs Bronwyn J. , Fullerton Janice M. , Roberts Gloria , Mitchell Philip B. , Andreassen Ole A. , Andreazza Ana C. , Zandi Peter P. , Pham Daniel , Biernacka Joanna M. , Frye Mark A. ,   The FACE‐BD Collaborators, The Global Bipolar Cohort Collaborative
Published: July 2023

Objectives

To understand treatment practices for bipolar disorders (BD), this study leveraged the Global Bipolar Cohort collaborative network to investigate pharmacotherapeutic treatment patterns in multiple cohorts of well‐characterized individuals with BD in North America, Europe, and Australia.

Methods

Data on pharmacotherapy, demographics, diagnostic subtypes, and comorbidities were provided from each participating cohort. Individual site and regional pooled proportional meta‐analyses with generalized linear mixed methods were conducted to identify prescription patterns.

Results

This study included 10,351 individuals from North America (n = 3985), Europe (n = 3822), and Australia (n = 2544). Overall, participants were predominantly female (60%) with BD‐I (60%; vs. BD‐II = 33%). Cross‐sectionally, mood‐stabilizing anticonvulsants (44%), second‐generation antipsychotics (42%), and antidepressants (38%) were the most prescribed medications. Lithium was prescribed in 29% of patients, primarily in the Australian (31%) and European (36%) cohorts. First‐generation antipsychotics were prescribed in 24% of the European versus 1% in the North American cohort. Antidepressant prescription rates were higher in BD‐II (47%) compared to BD‐I (35%). Major limitations were significant differences among cohorts based on inclusion/exclusion criteria, data source, and time/year of enrollment into cohort.

Conclusions

Mood‐stabilizing anticonvulsants, second‐generation antipsychotics, and antidepressants were the most prescribed medications suggesting prescription patterns that are not necessarily guideline concordant. Significant differences exist in the prescription practices across different geographic regions, especially the underutilization of lithium in the North American cohorts and the higher utilization of first‐generation antipsychotics in the European cohorts. There is a need to conduct future longitudinal studies to further explore these differences and their impact on outcomes, and to inform and implement evidence‐based guidelines to help improve treatment practices in BD.
Review: Adverse event monitoring and reporting in studies of pediatric psychosocial interventions: a systematic review
Authors: Lodewyk Kalee , Bagnell Alexa , Courtney Darren B. , Newton Amanda S.
Published: July 2023

Background

Adverse event monitoring in studies of psychotherapy is crucial to clinical decision‐making, particularly for weighing of benefits and harms of treatment approaches. In this systematic review, we identified how adverse events are defined, measured, and reported in studies of psychosocial interventions for children with mental disorders.

Method

Medline, PsycINFO, Embase, ProQuest Dissertations and Theses Global, and the Cochrane Library were searched from January 2011–January 2023, and Google Scholar from January 2011–February 2023. English language experimental and quasi‐experimental studies that evaluated the efficacy or effectiveness of psychosocial interventions for childhood mental disorders were included. Information on the definition, assessment, and report of adverse events was extracted using a checklist based on Good Clinical Practice guidelines.

Results

In this review, 117 studies were included. Studies most commonly involved treating anxiety disorders or obsessive‐compulsive disorder (32/117; 27%); 44% of the experimental interventions tested (52/117) were cognitive behavioral therapies. Adverse events were monitored in 36 studies (36/117; 31%) with a protocol used in 19 of these studies to guide monitoring (19/36; 53%). Twenty‐seven different events were monitored across the studies with hospitalization the most frequently monitored (3/36; 8%). Event severity was fully assessed in 6 studies (17%) and partially assessed in 12 studies (33%). Only 4/36 studies (11%) included assessing events for cause.

Conclusions

To date, adverse events have been inconsistently defined, measured and reported in psychosocial intervention studies of childhood mental health disorders. Information on adverse events is an essential knowledge component for understanding the potential impacts and risks of therapeutic interventions.
Progress in elementary school reading linked to growth of cortical responses to familiar letter combinations within visual word forms
Authors: Wang Fang , Kaneshiro Blair , Toomarian Elizabeth Y. , Gosavi Radhika S. , Hasak Lindsey R. , Moron Suanna , Nguyen Quynh Trang H. , Norcia Anthony M. , McCandliss Bruce D.
Published: July 2023

Learning to read depends on the ability to extract precise details of letter combinations, which convey critical information that distinguishes tens of thousands of visual word forms. To support fluent reading skill, one crucial neural developmental process is one's brain sensitivity to statistical constraints inherent in combining letters into visual word forms. To test this idea in early readers, we tracked the impact of two years of schooling on within‐subject longitudinal changes in cortical responses to three different properties of words: coarse tuning for print, and fine tuning to either familiar letter combinations within visual word forms or whole word representations. We then examined how each related to growth in reading skill. Three stimulus contrasts—words versus pseudofonts, words versus pseudowords, pseudowords versus nonwords—were presented while high‐density EEG Steady‐State Visual Evoked Potentials (SSVEPs,n = 31) were recorded. Internalization of abstract visual word form structures over two years of reading experience resulted in a near doubling of SSVEP amplitude, with increasing left lateralization. Longitudinal changes (decreases) in brain responses to such word form structural information were linked to the growth in reading skills, especially in rapid automatic naming of letters. No such changes were observed for whole word representation processing and coarse tuning for print. Collectively, these findings indicate that sensitivity to visual word form structure develops rapidly through exposure to print and is linked to growth in reading skill.

Research Highlights

Longitudinal changes in cognitive responses to coarse print tuning, visual word from structure, and whole word representation were examined in early readers.

Visual word form structure processing demonstrated striking patterns of growth with nearly doubled in EEG amplitude and increased left lateralization.

Longitudinal changes (decreases) in brain responses to visual word form structural information were linked to the growth in rapid automatic naming for letters.

No longitudinal changes were observed for whole word representation processing and coarse tuning for print.
“We'd really love to but we're really busy”: Silence, precarity and resistance as structural barriers to anti‐racism in nursing education
Authors: Bell Blythe Victoria
Published: July 2023

Aim

To identify structural barriers to the uptake and practice of anti‐racism in nursing education, specifically in the Canadian context.

Design

A deconstructive, critical, qualitative inquiry informed by critical race theory, critical whiteness, feminism and post‐colonialism.

Methods

This study employed an anonymous online open‐ended questionnaire and online focus groups with Canadian nurse educators from April to June 2021. The data were analysed through a contextualist thematic analysis that accounts for data as essential experience and also a product of discourse.

Results

Structural barriers identified are organized into themes of: the academic environment; position and power; racism; program delivery; and Whiteness. Pervasive silence, especially white silence, can be interpreted in related contexts of precarity, self‐interest and institutional violence. Overarching processes of precarity and resistance exert power over the environment of nursing education which act to destabilize, disrupt and discourage anti‐racist efforts and education.

Conclusion

The sustainability of anti‐racism should be a primary focus. This entails attending to structures in nursing and higher education that make nursing education precarious work, especially for educators racialized as Other in the white supremacist racial binary of White: non‐White. Explicit and ongoing attention to conditions that silence is necessary for any progress to be made. Strategies of applying anti‐racism need to be as complex as the barriers.

Implications

Many schools of nursing are engaged in attempts to include anti‐racism as learning and environment. The structural barriers that interfere with effective integration of anti‐racism as a lens for nursing education must be named and addressed so educators and schools can be successful. The implication of trying to incorporate anti‐racism without addressing the barriers is a very superficial or pocketed application of anti‐racism, and a continuation of the status quo that reproduces Whiteness and excludes and harms people racialized otherwise.

Impact

The study addressed both strategies and barriers to anti‐racism in nursing education. This article addressed structural barriers in anti‐racism in Canadian nursing education. The main findings are that processes of precarity specific to nursing education in institutions of higher learning, and resistance through Whiteness, decision‐making hierarchy and regulatory structures interfere with the application of anti‐racism. This research impacts nurse educators in all nursing schools and leaders in higher education. It also impacts all current and future nursing students as the recipients of the education we provide.

Reporting Method

The paper adheres to COREQ checklist.

Patient or Public Contribution

No patient or public contribution.
Adenosine deaminase 2 deficiency in a Chinese patient: Report of one novel mutation and literature review
Authors: Yuxuan Bai , Yan Duan
Published: July 2023

Objective

Through a case of deficiency of adenosine deaminase 2 (DADA2) to improve domestic clinicians' understanding of the disease, and to review the literature, promote dermatologists for clinical secondary primary lesion diagnosis.

Method

Analysis of a case diagnosed with DADA2 deficiency of clinical manifestations, laboratory, imaging examination and treatment methods, and discussion through literature analysis.

Results

The child with recurrent fever, limbs nodular erythema, gradually in the limbs. CT of lower limb skin showed mild edema of the spinous layer, intact basal layer, dilated vascular congestion in the superficial dermis, visible RBC extravasation, and changes of telangiectasia ring purpura were considered. Cranial magnetic resonance imaging (MRI) showed a left choroidal cleft cyst. Genetic test was the CECR1 mutation. The treatment with adalimumab was effective.

Conclusion

In this case, DADA2 is the seventh case in China, and the CECR1 mutation site (c.254A> T p.N85I,c.851G>T p. G284V) was a compound heterozygous mutation. Mastering the clinical characteristics is helpful for clinicians to diagnose this disease.
Seasonal gene expression signatures of delayed fertilization in Fagaceae
Authors: Satake Akiko , Ohta Kayoko , Takeda‐Kamiya Noriko , Toyooka Kiminori , Kusumi Junko
Published: July 2023

In the family Fagaceae, fertilization is delayed by several weeks to 1 year after pollination, leading to 1‐ or 2‐year fruiting species depending on whether fruiting occurs in the same or the next year after flowering. To investigate physiological responses underlying the regulation of delayed fertilization, we monitored seasonal changes in genome‐wide gene expression in tissues including leaves and buds over 2 years under natural conditions in one‐ (Quercus glauca) and 2‐year fruiting species (Lithocarpus edulis). Genes associated with metabolic changes in response to winter cold, photosynthesis and cell proliferation, which are essential for survival and growth, showed highly conserved seasonal expression profiles between species. However, seasonal expression profiles diverged between species in genes associated with pollination, an important process contributing to the origin and maintenance of the reproductive barrier between plant species. By comparing seasonal progression of ovule development and gene expression in pistillate flowers, we revealed that ovules started developing after winter in the 2‐year fruiting species, which could be linked to the activation of genes involved in fertilization and female gametophyte development after winter. These findings suggest that the 2‐year fruiting species may have evolved a requirement of winter cold to prevent fertilization before winter and facilitate fertilization and embryo development in the following spring when temperature rises. This study offers new possibilities to explore the evolution of reproductive strategies in Fagaceae.
In defense of guilt‐tripping
Authors: Achs Rachel
Published: July 2023

It is tempting to hold that guilt‐tripping is morally wrong, either because it is objectionably manipulative, or because it involves gratuitously aiming to make another person suffer, or both. In this article, I develop a picture of guilt according to which guilt is a type of pain that incorporates a commitment to its own justification on the basis of the subject's wrongdoing. This picture supports the hypothesis that feeling guilty is an especially efficient means for a wrongdoer to come to more deeply understand why her behavior was wrong; it is precisely because guilt is painful and involves a self‐reflexive justificatory element that it is able to play this role. Such a picture, moreover, preserves the possibility that deliberately making others feel guilty needn't involve aiming gratuitously to harm them and needn't be objectionably manipulative. It follows that we should be surprisingly sanguine about the practice of inducing guilt in wrongdoers as a means of facilitating their moral edification.
The phosphoinositide signature guides the final step of plant cytokinesis
Authors: Lebecq Alexis , Goldy Camila , Fangain Aurélie , Gascon Elsa , Belcram Katia , Pastuglia Martine , Bouchez David , Caillaud Marie-Cécile
Published: July 2023

Plant cytokinesis, which fundamentally differs from that in animals, requires the outward expansion of a plasma membrane precursor named the cell plate. How the transition from a cell plate to a plasma membrane occurs remains poorly understood. Here, we report that the acquisition of plasma membrane identity occurs through lateral patterning of the phosphatidylinositol 4,5-bisphosphate PI(4,5)P
2
at the newly formed cell plate membrane. There, the phosphoinositide phosphatase SAC9 emerges as a key regulator, colocalizing with and regulating the function of the microtubule-associated protein MAP65-3 at the cell plate leading zone. In
sac9-3
mutant, the polar distribution of PI(4,5)P
2
at the cell plate is altered, leading to ectopic recruitment of the cytokinesis apparatus and formation of an additional cell plate insertion site. We propose that at the cell plate, SAC9 drives the depletion of PI(4,5)P
2
, which acts as a polar cue to spatially separate cell plate expansion from the acquisition of plasma membrane identity during final step of cytokinesis.
Identifying and Categorizing Challenges in Large-Scale Agile Software Development Projects: Insights from Two Swedish Companies
Authors: Saeeda Hina , Ahmad Muhammad Ovais , Gustavsson Tomas
Published: July 2023

We conducted a case study to examine the challenges encountered in large-scale agile development (LSAD) within two Swedish software companies. While agile methodologies have proven successful in small and medium-sized projects, their implementation in large-scale software development projects can be problematic. To identify these challenges, we employed thematic analysis, which revealed a total of 26 distinct challenges. These challenges were categorized into three main themes: Processes and practices, Teams, and Organizational-level challenges in LSAD. By recognizing and addressing these challenges, projects operating in similar contexts can synchronize their activities and harness the advantages of agile methodologies at a large scale. The article delves into comprehensive discussions on these challenges, offering valuable insights and directions for future research endeavors.
Adaptive walking assistance does not impact long-range stride-to-stride autocorrelations in healthy people
Authors: Otlet Virginie , Ronsse Renaud
Published: July 2023

This study is the first that investigates the effects of a wearable active pelvis orthosis using an oscillator-based adaptive assistance on the level of long-range autocorrelations in series of stride durations during overground walking. It is also the first to compare the effects of different assistance settings on spatiotemporal gait metrics.
LINC01088/miR-22/CDC6 Axis Regulates Prostate Cancer Progression by Activating the PI3K/AKT Pathway
Authors: Li Jianwei , Huang Xinghua , Chen Haodong , Gu Caifu , Ni Binyu , Zhou Jianhua
Published: July 2023

Background. Prostate cancer (PCa) harms the male reproductive system, and lncRNA may play an important role in it. Here, we report that the LINC01088/microRNA- (miRNA/miR-) 22/cell division cycle 6 (CDC6) axis regulated through the phosphatidylinositide 3-kinases- (PI3K-) protein kinase B (AKT) signaling pathway controls the development of PCa. Methods. lncRNA/miRNA/mRNA associated with PCa was downloaded and analyzed by Gene Expression Omnibus. The expression and correlation of LINC01088/miR-22/CDC6 in PCa were analyzed and verified by RT-qPCR. Dual-luciferase was used to analyze the binding between miR-22 and LINC01088 or CDC6. Cell Counting Kit-8 and Transwell were used to analyze the effects of LINC01088/miR-22/CDC6 interactions on PCa cell viability or migration/invasion ability. Localization of LINC01088 in cells was analyzed by nuclear cytoplasmic separation. The effect of LINC01088/miR-22/CDC6 interaction on downstream PI3K/AKT signaling was analyzed by Western blot. Results. LINC01088 or CDC6 was upregulated in prostate tumor tissues or cells, whereas miR-22 was downregulated, miR-22 directly targets both LINC01088 and CDC6. si-LINC01088 inhibits the PCa process by suppressing the PI3K/AKT pathway. CDC6 reverses si-linc01088-mediated cell growth inhibition and reduction of PI3K and AKT protein levels. Conclusion. Our results demonstrate that the LINC01088/miR-22/CDC6 axis functions in PCa progression and provide a promising diagnostic and therapeutic target.
Comparison of Hospital Performance in Acute Ischemic Stroke Based on Mortality and Functional Outcome in South Korea
Authors: Yang Bosco Seong Kyu , Jang Minuk , Lee Keon-Joo , Kim Beom Joon , Han Moon-Ku , Kim Joon-Tae , Choi Kang-Ho , Cha Jae-Kwan , Kim Dae-Hyun , Kim Dong-Eog , Ryu Wi-Sun , Park Jong-Moo , Kang Kyusik , Lee Soo Joo , Kim Jae Guk , Oh Mi-Sun , Yu Kyung-Ho , Lee Byung-Chul , Hong Keun-Sik , Cho Yong-Jin , Choi Jay Chol , Park Tai Hwan , Lee Kyung Bok , Kwon Jee-Hyun , Kim Wook-Joo , Sohn Sung Il , Hong Jeong-Ho , Lee Jun , Lee Sang-Hwa , Lee Ji Sung , Lee Juneyoung , Gorelick Philip B. , Bae Hee-Joon ,   on the behalf of the CRCS-K (Clinical Research Collaboration for Stroke in Korea) investigators*
Published: July 2023

BACKGROUND:

Recent evidence suggests a correlation between modified Rankin Scale-based measures, an outcome measure commonly used in acute stroke trials, and mortality-based measures used by health agencies in the evaluation of hospital performance. We aimed to examine whether the 2 types of measures are interchangeable in relation to evaluation of hospital performance in acute ischemic stroke.

METHODS:

Five outcome measures, unfavorable functional outcome (3-month modified Rankin Scale score ≥2), death or dependency (3-month modified Rankin Scale score ≥3), 1-month mortality, 3-month mortality, and 1-year mortality, were collected for 8292 individuals who were hospitalized for acute ischemic stroke between January 2014 and May 2015 in 14 hospitals participating in the Clinical Research Collaboration for Stroke in Korea – National Institute of Health registry. Hierarchical regression models were used to calculate per-hospital risk-adjusted outcome rates for each measure. Hospitals were ranked and grouped based on the risk-adjusted outcome rates, and the correlations between the modified Rankin Scale-based and mortality-based ranking and their intermeasure reliability in categorizing hospital performance were analyzed.

RESULTS:

The comparison between the ranking based on the unfavorable functional outcome and that based on 1-year mortality resulted in a Spearman correlation coefficient of −0.29 and Kendall rank coefficient of −0.23, and the comparison of grouping based on these 2 types of ranks resulted in a weighted kappa of 0.123 for the grouping in the top 33%/middle 33%/bottom 33% and 0.25 for the grouping in the top 20%/middle 60%/bottom 20%, respectively. No significant correlation or similarity in grouping capacities were found between the rankings based on the functional outcome measures and those based on the mortality measures.

CONCLUSIONS:

This study shows that regardless of clinical correlation at an individual patient level, functional outcome-based measures and mortality-based measures are not interchangeable in the evaluation of hospital performance in acute ischemic stroke.
Positive association between weight-adjusted-waist index and dementia in the Chinese population with hypertension: a cross-sectional study
Authors: Zhou Wei , Xie Yanyou , Yu Lingling , Yu Chao , Bao Huihui , Cheng Xiaoshu
Published: July 2023

Purpose

The links between obesity and dementia remain equivocal. Therefore, this study aimed to explore the association between weight-adjusted waist index (WWI), a new anthropometric indicator reflecting obesity, and dementia in the Chinese population with hypertension.

Methods

A total of 10,289 participants with hypertension were enrolled in this cross-sectional study, a subset of the China H-type hypertension registry study. WWI was calculated as waist circumference (WC) divided by the square root of bodyweight. Mini-mental state examination (MMSE) scale was performed to evaluate the cognitive function. According to educational background, different MMSE cut-off values were applied to define dementia: < 24 for participants with ≥ 7 years of education, < 20 for those with 1–6 years of education, and < 17 for illiterate participants. Multivariable linear regression and multivariable binary logistic regression analyses were conducted to assess the associations between WWI and MMSE and dementia, respectively.

Results

Overall, the mean age was 63.7 ± 9.7 years, and 49.0% were males. Multivariate linear regression analyses showed that WWI was negatively associated with MMSE (β, -1.09; 95% confidence interval [CI]: -1.24, -0.94). Consistently, multivariable binary logistic regression analyses found a positive association between WWI and the risk of dementia (odds ratio [OR], 1.45; 95% CI: 1.35, 1.56). Compared with individuals in quartile 1 of WWI, the adjusted β and OR values of WWI for MMSE and dementia were -2.28 (95% CI: -2.62, -1.94) and 2.12 (95% CI: 1.81, 2.48), respectively. Results of smoothing curve fitting confirmed the linear association between WWI and MMSE and dementia. Subgroup analysis showed a stronger association between WWI and dementia in participants with hypertension with midday napping.

Conclusion

WWI was independently and positively associated with dementia among the population with hypertension, especially in those with midday napping. The data suggests that WWI may serve as a simple and effective tool for the assessment of the risk of dementia in clinical practice.
A qualitative interview study applying the COM-B model to explore how hospital-based trainers implement antimicrobial stewardship education and training in UK hospital-based care
Authors: Turner Rebecca , Hart Jo , Ashiru-Oredope Diane , Atkins Lou , Eades Christopher , Felton Tim , Howlett Emily , Rice Stephen , Shallcross Laura , Lorencatto Fabiana , Byrne-Davis Lucie
Published: July 2023

Background

Antimicrobial resistance (AMR) is a major global health threat caused by the inappropriate use of antimicrobials in healthcare and other settings. Antimicrobial stewardship (AMS) is a broad multi-component health services intervention that promotes and monitors the judicious use of antimicrobials to preserve their future effectiveness. A main component of AMS is education and training (E&T). However, there are often discrepancies in how such interventions are implemented and delivered in hospital-based care. The aim of this study was to explore the factors influencing the implementation of AMS E&T in UK hospitals.

Methods

Semi-structured interviews were carried out with AMS E&T trainers in UK hospitals. The interview schedule was developed using the Capability, Opportunity, Motivation = Behaviour (COM-B) model. Participants were identified via professional networks and social media. Interviews were analysed using inductive thematic analysis, followed by deductive analysis using the COM-B model as a framework.

Results

A total of 34 participants (26 antimicrobial pharmacists, 3 nurses, 1 advanced clinical practitioner, 2 infectious disease consultants, 1 microbiologist and 1 clinical scientist). responsible for designing, implementing and evaluating AMS E&T in UK hospitals (five from Northern Ireland, four from Wales, two from Scotland and 23 from England) took part in virtual interviews. Key themes were: (1) The organisational context, including system-level barriers to AMS included competing organisational targets (Reflective motivation and physical opportunity) and the impact of the COVID-19 pandemic on activity (Physical opportunity); (2) Healthcare professionals’ roles and the wider multi-disciplinary team, such that AMS roles were defined and addressed poorly in E&T (Social opportunity); and (3) The individual perception of the need for AMS E&T in hospital-based care, manifest in a perceived lack of conviction of the wider threat of AMR and the resulting need for AMS E&T (Reflective motivation).

Conclusion

This study has identified factors influencing implementation of AMS E&T in UK hospitals and further identified where implemented, AMS E&T did not address real-world challenges. Current AMS E&T needs to be optimised to elicit practice change, with recommendations including training and engaging the wider work-force and drawing upon theoretically-informed intervention development frameworks to inform AMS E&T to better target AMS behaviour change.
Association of stress management behavior and diabetic self-care practice among diabetes type II patients in North Shoa Zone: a cross-sectional study
Authors: Eshete Akine , Mohammed Sadat , Deresse Tilahun , Kifleyohans Tewodros , Assefa Yibeltal
Published: July 2023

Background

The cornerstone of diabetes management is the self-care behavior of diabetics. However, many people with diabetes do not fully engage in these activities. Effective stress management behaviors have a positive impact on diabetes self-care. The purpose of this study was to investigate the relationship between self-care behaviors in people with diabetes and stress coping behaviors in people with type II diabetes.

Method

A facility-based cross-sectional study was undertaken in the North Shoa zone from March 2 to 29, 2022. The study involved 432 types II diabetic patients who were chosen at random from eight public hospitals. Eight item stress coping techniques tools was used to measure stress management behavior. Data were entered into Epi Data V.3.1 and analyzed using SPSS version 22. Data for continuous variables were reported as means and standard deviations and percentages for categorical variables. Descriptive statistic was used to summarize study variables. Binary logistic regression models were used to assess associations between sociodemographic variables, stress-coping behaviors, and self-care behaviors. Binary logistic regression model was used investigate the association between diabetic self-care behaviors and stress-coping behaviors. A p-value ≤ 0.05 and an OR with a 95% CI are considered statistically significant associations.

Result

the study showed that stress management behavior was observed in more than half of the patients (51.2; 95% CI; (46.5, 55.6). The study found that stress management behavior was associated with diabetic self-care practice (X2, 17.7; p < 0.0001). Patients with good stress management behavior (AOR = 2.0, 95% CI = (1.3, 3.0)), good perception (AOR = 2.3, 95% CI = (1.5, 3.4)), and family support (AOR = 2.3, 95% CI = (1.5, 3.6)) were more likely to conduct diabetes self-care.

Conclusion

This study shows that stress management behaviors and coping techniques are associated with self-care behavior and lead to significant improvements in diabetes self-care practices. Stress management and coping skills should be included in current systems as a common therapeutic service/treatment. Diabetes care practitioners should consider these factors when discussing diabetes self-management during consultations.