bluuebunny/crossref_metadata_2025 huggingface dataset:
Neurite orientation dispersion and density imaging quantifies microstructural impairment in the thalamus and its connectivity in amyotrophic lateral sclerosis
Authors: Cao Yun‐Bin , Wu Ye , Dong Qiu‐Yi , Huang Nao‐Xin , Zou Zhang‐Yu , Chen Hua‐Jun
Published: February 2024

Aims

To evaluate microstructural impairment in the thalamus and thalamocortical connectivity using neurite orientation dispersion and density imaging (NODDI) in amyotrophic lateral sclerosis (ALS).

Methods

This study included 47 healthy controls and 43 ALS patients, whose structural and diffusion‐weighted data were collected. We used state‐of‐the‐art parallel transport tractography to identify thalamocortical pathways in individual spaces. Thalamus was then parcellated into six subregions based on its connectivity pattern with the priori defined cortical (i.e., prefrontal/motor/somatosensory/temporal/posterior‐parietal/occipital) regions. For each of the thalamic and cortical subregions and thalamo‐cortical tracts, we compared the following NODDI metrics between groups: orientation dispersion index (ODI), neurite density index (NDI), and isotropic volume fraction (ISO). We also used these metrics to conduct receiver operating characteristic curve (ROC) analyses and Spearman correlation.

Results

In ALS patients, we found decreased ODI and increased ISO in the thalamic subregion connecting the left motor cortex and other extramotor (e.g., somatosensory and occipital) cortex (Bonferroni‐corrected p < 0.05). NDI decreased in the bilateral thalamo‐motor and thalamo‐somatosensory tracts and in the right thalamo‐posterior‐parietal and thalamo‐occipital tracts (Bonferroni‐corrected p < 0.05). NDI reduction in the bilateral thalamo‐motor tract (p = 0.017 and 0.009) and left thalamo‐somatosensory tract (p = 0.029) was correlated with disease severity. In thalamo‐cortical tracts, NDI yielded a higher effect size during between‐group comparisons and a greater area under ROC (p < 0.05) compared with conventional diffusion tensor imaging metrics.

Conclusions

Microstructural impairment in the thalamus and thalamocortical connectivity is the hallmark of ALS. NODDI improved the detection of disrupted thalamo‐cortical connectivity in ALS.
From moral rights to legal rights? Lessons from healthcare contexts
Authors: Da Silva Michael
Published: February 2024

Many believe the existence of a moral right to some good should lead to recognition of a corresponding legal right to that good. If, for instance, there is a moral right to healthcare, it is natural to believe countries should recognize a legal right to healthcare. This article demonstrates that justifying legal rights to healthcare is more difficult than many assume. The existence of a moral right is insufficient to justify recognition of a corresponding justiciable constitutional right. Further conditions on when it is appropriate to recognize constitutional rights are rarely satisfied in the healthcare case. And focusing on aspirational or statutory rights presents costs for those seeking to justify legal rights on the basis of corresponding moral ones while maintaining empirical challenges for justifying constitutional rights. This suggests movement from a moral right to a corresponding legal one is far from straightforward and justifies examining alternative means of realizing moral socio‐economic rights such as the proposed moral right to healthcare.
An artificial intelligence‐driven predictive model for pediatric allogeneic hematopoietic stem cell transplantation using clinical variables
Authors: Echecopar Carlos , Abad Inés , Galán‐Gómez Víctor , Mozo del Castillo Yasmina , Sisinni Luisa , Bueno David , Ruz Beatriz , Pérez‐Martínez Antonio
Published: February 2024

Background

Hematopoietic stem cell transplantation (HSCT) is a procedure with high morbidity and mortality. Identifying patients for maximum benefit and risk assessment is crucial in the decision‐making process. This has led to the development of predictive risk models for HSCT in adults, which have limitations when applied to pediatric population. Our goal was to develop an automatic learning algorithm to predict survival in children with malignant disorders undergoing HSCT.

Methods

We studied allogenic HSCTs performed on children with malignant disorders at a third‐level hospital between 1991 and 2021. Survival was analyzed using the Kaplan–Meier method, log‐rank test for the univariate analysis, and Cox regression for the multivariate analysis. A prognostic index was constructed based on these findings. Lastly, we constructed a predictive model using a random forest algorithm to forecast 1‐year survival after HSCT.

Results

We analyzed 229 HSCTs in 201 patients with a median follow‐up of 1.64 years. Variables that impacted on the multivariate analysis were older age (hazard ratio [HR] 1.40, 95% confidence interval [CI] 1.12–1.76, p = .003), oldest period of HSCT (HR 0.46, 95% CI 0.29–0.73, p < .001), and mismatched donor (HR 2.65, 95% CI 1.51–4.65, p = .001). Our prognostic index was associated with 3‐year overall survival (OS; p < .001). A random forest was developed using as variables: diagnosis, age, year of HSCT, time from diagnosis to HSCT, disease stage, donor type, and conditioning. This achieved 72% accuracy in predicting 1‐year OS.

Conclusions

Our index and random forest was effective in predicting 1‐year survival. However, further validation in diverse populations is necessary to establish their generalizability.
An Automated Item Pool Assembly Framework for Maximizing Item Utilization for CAT
Authors: Lim Hwanggyu , Han Kyung (Chris) T.
Published: February 2024

Computerized adaptive testing (CAT) has gained deserved popularity in the administration of educational and professional assessments, but continues to face test security challenges. To ensure sustained quality assurance and testing integrity, it is imperative to establish and maintain multiple stable item pools that are consistent in terms of psychometric characteristics and content specifications. This study introduces the Honeycomb Pool Assembly (HPA) framework, an innovative solution for the construction of multiple parallel item pools for CAT that maximizes item utilization in the item bank. The HPA framework comprises two stages—cell assembly and pool assembly—and uses a mixed integer programming modeling approach. An empirical study demonstrated HPA's effectiveness in creating a large number of parallel pools using a real‐world high‐stakes CAT assessment item bank. The HPA framework offers several advantages, including (a) simultaneous creation of multiple parallel pools, (b) simplification of item pool maintenance, and (c) flexibility in establishing statistical and operational constraints. Moreover, it can help testing organizations efficiently manage and monitor the health of their item banks. Thus, the HPA framework is expected to be a valuable tool for testing professionals and organizations to address test security challenges and maintain the integrity of high‐stakes CAT assessments.
Dietary metabarcoding of keystone sardine species reveals the importance of their ichthyoplankton prey in food webs of the Southern Brazilian Bight fisheries
Authors: de Queiroz Anna Karolina Oliveira , Gasalla Maria A. , Laux Marcele , Oliveira Renato Renison Moreira , dos Anjos Santa Rosa Fabricio , Schrøder‐Nielsen Audun , Postuma Felippe A. , de Luna Sales João Bráullio , de Boer Hugo J. , Mauvisseau Quentin , Ready Jonathan Stuart
Published: February 2024

Clupeiform fishes are ecologically and economically important species contributing to industrial and artisanal fisheries worldwide. They represent key links in food webs, influencing the dynamic between trophic levels. The dietary interactions of these species are poorly studied in many regions, yet essential for fisheries management. To elucidate the role of these species in food webs of the Southern Brazilian Bight pelagic fisheries, we used metabarcoding analysis of fish stomach contents of Clupeiformes and possible predators. Onboard sampling from March to September 2016 allowed for processing of 87 stomach samples representing 31 species (including 12 samples representing three species of Clupeiformes). Links between trophic levels showed the predominance of Sardinella brasiliensis and Engraulis anchoita as important dietary items of a large range of fishes (28 species belonging to 18 families) and representing the majority of the total prey read abundance assigned to clupeiform fishes (~46% and ~32%, respectively). Opisthonema oglinum contributed to the diet of 16 species in 13 families and ~18% of total read abundance of clupeiform fishes as prey. The appearance of multiple clupeiform taxa in the diet of predators that are not commonly associated with pelagic prey indicates that ecosystem‐based fisheries management should not be separated between pelagic and demersal fisheries. The diet of Clupeiformes revealed an unexpectedly large diversity of fish species and a low proportion of invertebrates (<5% of clupeiform prey reads). This was likely due to a combination of both a limitation of the metabarcoding method (primer bias and low success of invertebrate taxonomic identification) as well as a contribution of early life stages (ichthyoplankton) to the diet of these fishes. The potential role of clupeiform fish populations as a constraint to the recruitment from the ichthyoplanktonic phase of other ecologically or commercially important fishes should be considered as an important direction for future studies.
“Stories one tells in dark times”: Fabulation, fugitivity, and futurity in Olivia Wenzel's 1000 Serpentinen Angst
Authors: Roca Lizarazu Maria
Published: February 2024

This article engages with aesthetic acts of experimentation in Olivia Wenzel's 1000 Serpentinen Angst. Building on recent scholarship on the politics of aesthetics in Wenzel's text, I argue that these experiments are intertwined with key themes in the book, particularly issues of racialization and of Black (im‐)possibility in present‐day Germany. In this context, my article focuses on a largely overlooked aspect of Wenzel's text, namely its surreal, fantastical, and speculative elements. Drawing on Tavia Nyong'o and Saidiya Hartman's notion of “(critical) fabulation,” I propose that Wenzel's writing mobilizes fantastic, imaginative, and speculative elements to unsettle oppressive realities and realisms in favor of alternative modes of world‐ and future‐making. Inspired by Tina M. Campt's work, I conceptualize these re‐makings as “fugitive” and quotidian strategies, developed in response to a broken world, which still have the potential to generate new infrastructures for relationality and futurity.
Eradication rate and adherence with high‐dose amoxicillin and proton pump inhibitor as first‐line treatment for Helicobacter pylori infection: Experience from University Hospital in Chile
Authors: von Muhlenbrock Christian , Cordova Andrea , Nuñez Paulina , Pacheco Nicole , Herrera Karin , Quera Rodrigo
Published: February 2024

Introduction

In Chile, more than 70% of adults are infected by Helicobacter pylori. Clarithromycin should not be used in any regimen if there is >15% resistance to this antibiotic, being greater than 26% in our population. In this scenario, the effectiveness of triple therapy (proton pump inhibitor [PPI], clarithromycin, amoxicillin) was only 63.8%.

Aim

To evaluate the eradication rate and safety of dual therapy (esomeprazole and amoxicillin) in high doses, through a prospective, observational, and descriptive study.

Methods

Patients with a positive urease test obtained in an upper digestive endoscopy were included. Any other previous H. pylori eradication regimen were excluded. All patients were treated with esomeprazole 40 mg three times a day and amoxicillin 750 mg four times a day for 14 days. The eradication rate of the dual therapy was evaluated with the H. pylori stool antigen test (the Pylori‐Strip® test used) 6 weeks after completing the eradication treatment and with at least 14 days without PPI, being a negative result, confirmation of the effectiveness of this regimen.

Results

Of 122 patients, 106 had a negative H. pylori antigen in stool; The intention‐to‐treat and per protocol analysis, the eradication rates were 91.8% [95% CI: 87%–97%] and 94% [95% CI: 90%–98%], respectively. Four patients discontinued treatment due to adverse effects. Smoking and adherence to treatment were associated with eradication rate.

Conclusions

In this cohort of patients with H. pylori infection, high‐dose dual therapy has a high eradication rate and good adherence, raising the possibility that it could be used as first‐line therapy in our country. Studies with a larger number of patients should confirm these results.
Does targeted recruitment turn the dial for gender equity? A qualitative study at an Australian University
Authors: Lane C. , Saronga N. , Fowell R. , Berretta R. , Blackmore K. , Momenzadeh L. , Giacomini A. , Ware S. , Milam J.
Published: February 2024

This qualitative study explored a targeted recruitment initiative that was designed to attract and recruit female academic staff in STEM disciplines at an Australian University. Semi‐structured, one‐on‐one interviews were conducted with female and male key informants: 16 Panel Members and six Applicants. Codebook Thematic Analysis was applied using a feminist methodological lens. Results showed several themes (categorised as barriers and facilitators) impacting the implementation and success of targeted recruitment. The majority of themes were associated with Panel Members, underpinning the importance of panels' support for targeted recruitment. Nearly all barriers were gender‐related, disadvantaging female applicants and emphasising a need to address gender inequity broadly. Key recommendations for future improvement were strategies to improve the support of panels (e.g., gender bias training, improved communication of responsibilities in targeted recruitment and ensuring an equity and diversity ‘champion’) and efforts to strengthen the positive diversity reputation of the University.
Comparison of patient background between a real‐world North American cohort and the Göteborg‐2 trial
Authors: Chiarelli Giuseppe , Davis Matthew , Stephens Alex , Cirulli Giuseppe Ottone , Finati Marco , Corsi Nicholas J. , Sood Akshay , Tinsley Shane , Carrieri Giuseppe , Briganti Alberto , Montorsi Francesco , Lughezzani Giovanni , Buffi Nicolò , Rogers Craig , Abdollah Firas
Published: February 2024

Objectives

To analyze the generalizability of the Göteborg‐2 findings to a North American cohort.

Methods

We replicated the Göteborg‐2 inclusion criteria in our Henry Ford Health (HFH) cohort, by identifying all patients 50–60 years old who had a PSA test from 2013 to 2018. The first PSA within the study period was considered PSA at entry, and included in the analysis. Chi‐square test was used to compare categorical variables between the Göteborg‐2 and HFH cohort, with a particular focus on Black men, who were also analyzed separately.

Results

The HFH patients included in the cohort were 49 456, of which 8562 were Black. In patients within the entire HFH cohort, HFH Black cohort, Göteborg Reference cohort, and Göteborg Experimental cohort, the rate of PSA ≥3 ng/mL was, respectively, 6.8%, 10.2%, 6.8%, and 6.6%. The rate of biopsy performed was, respectively, 1.8%, 4.1%, 5.8%, and 2.5%. PCa was found in, respectively, 1.4%, 3.0%, 2.3%, and 1.5%; Gleason score 3 + 3 in, respectively, 0.5%, 0.8%, 1.2%, and 0.6%; Gleason score > 3 + 3 in, respectively, 0.9%, 2.2%, 1.1%, and 0.9%.

Conclusions

Our cohort had a lower biopsy rate and a lower incidence of non‐csPCa diagnosis than both Göteborg cohorts, while still maintaining the same incidence of csPCa. This implies that the benefits of reducing non‐csPCa diagnosis, as observed in the Experimental Göteborg cohort, are not necessarily replicable in U.S. “real‐world practice” patients. Also noteworthy, we had a significantly higher percentage of Black men, who showed more aggressive disease.
Bmo‐miR‐6498‐5p suppresses Bombyx mori nucleopolyhedrovirus infection by down‐regulating BmPLPP2 to modulate pyridoxal phosphate content in B. mori
Authors: Cao Hui‐Hua , Kong Wei‐Wei , Chen Xi‐Ya , Ayaz Sadaf , Hou Cai‐Ping , Wang Yi‐Sheng , Liu Shi‐Huo , Xu Jia‐ping
Published: February 2024

The RNA interference pathway mediated by microRNAs (miRNAs) is one of the methods to defend against viruses in insects. Recent studies showed that miRNAs participate in viral infection by binding to target genes to regulate their expression. Here, we found that the Bombyx mori miRNA, miR‐6498‐5p was down‐regulated, whereas its predicted target gene pyridoxal phosphate phosphatase PHOSPHO2 (BmPLPP2) was up‐regulated upon Bombyx mori nucleopolyhedrovirus (BmNPV) infection. Both in vivo and in vitro experiments showed that miR‐6498‐5p targets BmPLPP2 and suppresses its expression. Furthermore, we found miR‐6498‐5p inhibits BmNPV genomic DNA (gDNA) replication, whereas BmPLPP2 promotes BmNPV gDNA replication. As a pyridoxal phosphate (PLP) phosphatase (PLPP), the overexpression of BmPLPP2 results in a reduction of PLP content, whereas the knockdown of BmPLPP2 leads to an increase in PLP content. In addition, exogenous PLP suppresses the replication of BmNPV gDNA; in contrast, the PLP inhibitor 4‐deoxypyridoxine facilitates BmNPV gDNA replication. Taken together, we concluded that miR‐6498‐5p has a potential anti‐BmNPV role by down‐regulating BmPLPP2 to modulate PLP content, but BmNPV induces miR‐6498‐5p down‐regulation to promote its proliferation. Our findings provide valuable insights into the role of host miRNA in B. mori–BmNPV interaction. Furthermore, the identification of the antiviral molecule PLP offers a novel perspective on strategies for preventing and managing viral infection in sericulture.
Cross‐border mobility, inequality and migration intermediaries: Labour migration from Nepal to Malaysia
Authors: Sha Heila , Khor Yvonne
Published: February 2024

This article aims to contribute to labour recruitment policy by demonstrating the relations between cross‐border mobility and inequality through the lens of migration intermediaries. Drawing on thematic analysis of the MIDEQ project's in‐depth interviews with Nepalese labour migrants (n = 20) in Malaysia, this research reveals the range of migration intermediaries along the recruitment chain, and shows contradictory roles played by migration intermediaries: they help migrant workers access employment and other opportunities thus overcoming inequality in mobility, whilst simultaneously reproducing socio‐economic inequalities and the unequal power relations experienced by migrants. Hence, we identify a “middle space effect” that links migration processes with migration outcomes, reconstructing socio‐economic inequalities in mediated migration. We highlight the role of state policies regarding migration and labour in co‐producing such inequalities, and the embeddedness of middle space intermediaries in unequal global power dynamics, and we offer policy suggestions on regulation of labour recruitment and employment.
An objective comparative study of non‐surgical cleansing techniques and cleanser types in bacterial burden management
Authors: Oropallo Alisha , Rao Amit S. , Del Pin Christina , Ranire‐Maguire Marisa , Mathew Angelin
Published: February 2024

Cleansing is a vital component of effective wound hygiene and biofilm management, often accomplished through vigorous mechanical action or through soaking with moistened gauze. In the present study, a quantitative comparison of the effectiveness of different cleansing techniques and solutions in removing bacteria was conducted on 71 chronic wounds using bacterial fluorescence imaging as a real‐time diagnostic for moderate to high bacterial loads. Vigorous gauze cleansing for 30 s proved most effective by reducing bacterial fluorescence by 33.99%, surpassing 10‐min soaking in bacterial reduction (13.24%). Among different cleansers, no statistically significant differences in effectiveness were observed, but povidone‐iodine showed the strongest trend towards bacterial reduction. Sub‐analysis highlighted the superiority of antiseptic cleansers over saline and gentle soap (−33.30% vs. −1.80% bacterial reduction respectively). Five percent acetic acid was also shown to be more effective in removing specific bacterial strains (Pseudomonas aeruginosa). Findings from studies like this contribute to refining wound hygiene guidelines and clinical algorithms for bacterial and biofilm management.
Safety and efficacy of combined dilation/stenting of venous abnormalities, including complete obstructions, during lead extractions in patients with congenital heart disease
Authors: Knapp William P. , O'Leary Edward T. , Quinn Brian , Porras Diego , Mah Douglas Y.
Published: February 2024

Introduction

Management of transvenous leads in patients with congenital heart disease (CHD) can be complicated by venous obstructions and residual shunts. We present our experience performing concurrent lead extraction and dilation/stenting of venous pathways, including patients with complete venous obstruction.

Methods

All cases of concurrent lead extraction and recanalization of vena cavae/baffles between 2017 and 2021 at Boston Children's Hospital were retrospectively included and reviewed for safety and efficacy.

Results

Eight patients, 4 female, median 38.5 years of age (range 16.7−49 years) and 81.6 kg weight (range 41.3−97.8 kg) at time of procedure were included. All patients had CHD, a majority (n = 7) having transposition of the great arteries palliated via atrial switch. All leads were removed in their entirety, with most patients having two leads extracted (n = 7). Median lead dwell time was 13.8 years (range 3.6−35.3 years). Three patients had complete obstructions, three required stenting of their innominate veins and three required recanalization of their femoral vessels. Median procedure time was 9.8 h (range 5.4−12.8 h). Complications included blood transfusion (n = 2), arrhythmia (n = 3), pleural effusion (n = 1), and pressure ulcer (n = 1). There were no cardiac perforations, venous tears, or deaths.

Conclusion

Lead extraction along with dilation and stenting of venous anomalies, though long in duration, proved effective with minimal complications. This combined procedure can safely and effectively resolve complete obstructions secondary to transvenous leads.
Commentary: Integrative, multi‐level explanatory models are needed to understand recent trends in sex, gender, and internalizing conditions, reflections on Keyes and Platt (2023)
Authors: Shanahan Lilly , Copeland William E.
Published: February 2024

Keyes' and Platt's (The Journal of Child Psychology and Psychiatry, 2023) review provides much‐needed systematic evidence about why internalizing symptoms have increased and it clarifies the role of novel risk factors. The findings highlight that multiple factors at multiple levels are responsible for this phenomenon, many with small effects, within a complex interplay that is rarely well captured. As new insights emerge across disciplines, an important step is to renew efforts to integrate them to understand how internalizing symptoms develop for different people.
Embedding the service user voice to co‐produce UK mental health nurse education—A lived experience narrative
Authors: O'Brien Sam , Davenport Caroline
Published: February 2024

Accessible Summary

What is known on the subject?

Co‐production aims to value service user voices and is increasingly used in healthcare.

Less is known about how co‐production in nursing education is experienced by service users.

What the paper adds to existing knowledge?

This paper shares the experience of one service user who teaches student nurses in a UK university.

For the first author, the paper highlights that co‐producing nurse education has been valuable and rewarding for both a service user and students.

What are the implications for practice?

Co‐production has the potential to benefit student nurses, including challenging their perceptions of ‘difficult’ patients. To achieve this, teaching sessions must be equally produced and delivered. By employing and including service users, universities have the potential to improve experiences for students and service users alike.

Introduction

Co‐production is increasingly used in health care but there is less attention to a co‐produced mental health nurse education.

Aim

This article sought to explore the co‐production experiences of a service user who teaches mental health nurses, alongside the benefits of this to nurse education.

Methods

The article is a lived experience narrative co‐written with a nursing lecturer.

Thesis

Co‐produced mental health nurse education challenges students' perceptions towards self‐harm and encourages empathy and understanding of service user distress.

Implications for Practice

Co‐production has many benefits to nurse education including a positive student experience, and validation of the service user experience to support meaningful recovery.
Effect of amlodipine on the circulating renin‐angiotensin‐aldosterone system in healthy cats
Authors: Garcia Marrero Tatiana M. , Ward Jessica L. , Tropf Melissa A. , Bourgois‐Mochel Agnes , Guillot Emilie , Domenig Oliver , Yuan Lingnan , Kundu Debosmita , Mochel Jonathan P.
Published: February 2024

Background

Systemic hypertension (SH) is a common cardiovascular disease in older cats that is treated primarily with the calcium channel blocker amlodipine besylate (AML). The systemic effect of AML on the classical and alterative arms of the renin‐angiotensin‐aldosterone system (RAAS) in cats is incompletely characterized.

Hypothesis/Objectives

To determine the effect of AML compared to placebo on circulating RAAS biomarkers in healthy cats using RAAS fingerprinting.

Animals

Twenty healthy client‐owned cats.

Methods

Cats were administered amlodipine besylate (0.625 mg in toto) or placebo by mouth once daily for 14 days in a crossover design with a 4‐week washout period. Plasma AML concentrations and RAAS biomarker concentrations were measured at multiple timepoints after the final dose in each treatment period. Time‐weighted averages for RAAS biomarkers over 24 hours after dosing were compared between treatment groups using Wilcoxon rank‐sum testing.

Results

Compared to placebo, AML treatment was associated with increases in markers of plasma renin concentration (median 44% increase; interquartile range [IQR] 19%‐86%; P = .009), angiotensin I (59% increase; IQR 27‐101%; P = .006), angiotensin II (56% increase; IQR 5‐70%; P = .023), angiotensin IV (42% increase; −19% to 89%; P = .013); and angiotensin 1‐7 (38% increase; IQR 9‐118%; P = .015).

Conclusions and Clinical Importance

In healthy cats, administration of AML resulted in nonspecific activation of both classical and alternative RAAS pathways.
Cortical gradient perturbation in attention deficit hyperactivity disorder correlates with neurotransmitter‐, cell type‐specific and chromosome‐ transcriptomic signatures
Authors: Chen Zhiyi , Xu Ting , Liu Xuerong , Becker Benjamin , Li Wei , Xia Lei , Zhao Wenqi , Zhang Rong , Huo Zhenzhen , Hu Bowen , Tang Yancheng , Xiao Zhibing , Feng Zhengzhi , Chen Ji , Feng Tingyong
Published: February 2024

Aims

This study aimed to illuminate the neuropathological landscape of attention deficit hyperactivity disorder (ADHD) by a multiscale macro–micro‐molecular perspective from in vivo neuroimaging data.

Methods

The “ADHD‐200 initiative” repository provided multi‐site high‐quality resting‐state functional connectivity (rsfc‐) neuroimaging for ADHD children and matched typically developing (TD) cohort. Diffusion mapping embedding model to derive the functional connectome gradient detecting biologically plausible neural pattern was built, and the multivariate partial least square method to uncover the enrichment of neurotransmitomic, cellular and chromosomal gradient‐transcriptional signatures of AHBA enrichment and meta‐analytic decoding.

Results

Compared to TD, ADHD children presented connectopic cortical gradient perturbations in almost all the cognition‐involved brain macroscale networks (all pBH <0.001), but not in the brain global topology. As an intermediate phenotypic variant, such gradient perturbation was spatially enriched into distributions of GABAA/BZ and 5‐HT2A receptors (all pBH <0.01) and co‐varied with genetic transcriptional expressions (e.g. DYDC2, ATOH7, all pBH <0.01), associated with phenotypic variants in episodic memory and emotional regulations. Enrichment models demonstrated such gradient‐transcriptional variants indicated the risk of both cell‐specific and chromosome‐ dysfunctions, especially in enriched expression of oligodendrocyte precursors and endothelial cells (all pperm <0.05) as well enrichment into chromosome 18, 19 and X (pperm <0.05).

Conclusions

Our findings bridged brain macroscale neuropathological patterns to microscale/cellular biological architectures for ADHD children, demonstrating the neurobiologically pathological mechanism of ADHD into the genetic and molecular variants in GABA and 5‐HT systems as well brain‐derived enrichment of specific cellular/chromosomal expressions.
Unveiling terahertz wave stress effects and mechanisms in Pinellia ternata: Challenges, insights, and future directions
Authors: Wang Dongdong , Zheng Jiatong , Sarsaiya Surendra , Jin Leilei , Chen Jishuang
Published: February 2024

This review aims to elucidate the intricate effects and mechanisms of terahertz (THz) wave stress on Pinellia ternata, providing valuable insights into plant responses. The primary objective is to highlight the imperative for future research dedicated to comprehending THz wave impacts across plant structures, with a specific focus on the molecular intricacies governing root system structure and function, from shoots to roots. Notably, this review highlights the accelerated plant growth induced by THz waves, especially in conjunction with other environmental stressors, and the subsequent alterations in cellular homeostasis, resulting in the generation of reactive oxygen species (ROS) and an increase in brassinosteroids. Brassinosteroids are explored for their dual role as toxic by‐products of stress metabolism and vital signal transduction molecules in plant responses to abiotic stresses. The paper further investigates the spatio‐temporal regulation and long‐distance transport of phytohormones, including growth hormone, cytokinin, and abscisic acid (ABA), which significantly influence the growth and development of P. ternata under THz wave stress. With a comprehensive review of Reactive oxygen species (ROS) and Brassinosteroid Insensitive (BRI) homeostasis and signalling under THz wave stress, the article elucidates the current understanding of BRI involvement in stress perception, stress signalling, and domestication response regulation. Additionally, it underscores the importance of spatio‐temporal regulation and long‐distance transport of key plant hormones, such as growth hormone, cytokinin, and ABA, in determining root growth and development under THz wave stress. The study of how plants perceive and respond to environmental stresses holds fundamental biological significance, and enhancing plant stress tolerance is crucial for promoting sustainable agricultural practices and mitigating the environmental burdens associated with low‐tolerance crop cultivation.
Psychological risk factors predictive of suicidal distress in men receiving a community‐based brief psychological intervention
Authors: Hanlon Claire Anne , Saini Pooja , Boland Jane , McIlroy David , Poole Helen , Chopra Jennifer
Published: February 2024

Introduction

Adaptable community‐based approaches for assessment and delivery of suicide prevention interventions for men experiencing suicidal crisis are needed. The lay your cards on the table (LYCT) component of the James' Place Model is a novel therapeutic approach comprised of four sets of card variables that correspond with suicidal risk factors. This study investigated the LYCT in predicting suicidal distress among men.

Methods

Cross‐sectional data of 511 men aged 18–69 years (M = 34.59 years; SD = 12.30) collected between 1st August 2018 and 29th July 2021 were assessed to predict suicidal distress measured using the CORE Clinical Outcome Measures (CORE‐OM).

Results

From four categories comprising the LYCT, correlational analyses demonstrated that 20 associations emerged as statistically significant (r's = 0.12–0.19). When these were included in regression analyses, effect sizes explained 2%–5% variance in CORE‐OM outcomes (R2).

Conclusion

Use of LYCT is supported for engaging men in the assessment of suicide risk factors and to inform tailoring of intervention delivery to suit the individual needs of men experiencing suicidal crisis.
Pri peptides temporally coordinate transcriptional programs during epidermal differentiation
Authors: Gallois Maylis , Menoret Delphine , Marques-Prieto Simon , Montigny Audrey , Valenti Philippe , Moussian Bernard , Plaza Serge , Payre François , Chanut-Delalande Hélène
Published: February 2024

To achieve a highly differentiated state, cells undergo multiple transcriptional processes whose coordination and timing are not well understood. In
Drosophila
embryonic epidermal cells, polished-rice (Pri) smORF peptides act as temporal mediators of ecdysone to activate a transcriptional program leading to cell shape remodeling. Here, we show that the ecdysone/Pri axis concomitantly represses the transcription of a large subset of cuticle genes to ensure proper differentiation of the insect exoskeleton. The repression relies on the transcription factor Ken and persists for several days throughout early larval stages, during which a soft cuticle allows larval crawling. The onset of these cuticle genes normally awaits the end of larval stages when the rigid pupal case assembles, and their premature expression triggers abnormal sclerotization of the larval cuticle. These results uncovered a temporal switch to set up distinct structures of cuticles adapted to the animal lifestyle and which might be involved in the evolutionary history of insects.
An intramolecular cross-talk in D29 mycobacteriophage endolysin governs the lytic cycle and phage-host population dynamics
Authors: Nair Gokul , Jain Vikas
Published: February 2024

D29 mycobacteriophage encodes LysA endolysin, which mediates mycobacterial host cell lysis by targeting its peptidoglycan layer, thus projecting itself as a potential therapeutic. However, the regulatory mechanism of LysA during the phage lytic cycle remains ill defined. Here, we show that during D29 lytic cycle, structural and functional regulation of LysA not only orchestrates host cell lysis but also is critical for maintaining phage-host population dynamics by governing various phases of lytic cycle. We report that LysA exists in two conformations, of which only one is active, and the protein undergoes a host peptidoglycan–dependent conformational switch to become active for carrying out endogenous host cell lysis. D29 maintains a pool of inactive LysA, allowing complete assembly of phage progeny, thus helping avoid premature host lysis. In addition, we show that the switch reverses after lysis, thus preventing exogenous targeting of bystanders, which otherwise negatively affects phage propagation in the environment.
Stem cell mTOR signaling directs region-specific cell fate decisions during intestinal nutrient adaptation
Authors: Mattila Jaakko , Viitanen Arto , Fabris Gaia , Strutynska Tetiana , Korzelius Jerome , Hietakangas Ville
Published: February 2024

The adult intestine is a regionalized organ, whose size and cellular composition are adjusted in response to nutrient status. This involves dynamic regulation of intestinal stem cell (ISC) proliferation and differentiation. How nutrient signaling controls cell fate decisions to drive regional changes in cell-type composition remains unclear. Here, we show that intestinal nutrient adaptation involves region-specific control of cell size, cell number, and differentiation. We uncovered that activation of mTOR complex 1 (mTORC1) increases ISC size in a region-specific manner. mTORC1 activity promotes Delta expression to direct cell fate toward the absorptive enteroblast lineage while inhibiting secretory enteroendocrine cell differentiation. In aged flies, the ISC mTORC1 signaling is deregulated, being constitutively high and unresponsive to diet, which can be mitigated through lifelong intermittent fasting. In conclusion, mTORC1 signaling contributes to the ISC fate decision, enabling regional control of intestinal cell differentiation in response to nutrition.
Molecular recognition and activation of the prostacyclin receptor by anti-pulmonary arterial hypertension drugs
Authors: Wang James Jiqi , Jin Sanshan , Zhang Heng , Xu Youwei , Hu Wen , Jiang Yi , Chen Chen , Wang Dao Wen , Xu H. Eric , Wu Canrong
Published: February 2024

The prostacyclin (PGI
2
) receptor (IP) is a G
s
-coupled receptor associated with blood pressure regulation, allergy, and inflammatory response. It is a main therapeutic target for pulmonary arterial hypertension (PAH) and several other diseases. Here we report cryo–electron microscopy (cryo-EM) structures of the human IP-G
s
complex bound with two anti-PAH drugs, treprostinil and MRE-269 (active form of selexipag), at global resolutions of 2.56 and 2.41 angstrom, respectively. These structures revealed distinct features governing IP ligand binding, receptor activation, and G protein coupling. Moreover, comparison of the activated IP structures uncovered the mechanism and key residues that determine the superior selectivity of MRE-269 over treprostinil. Combined with molecular docking and functional studies, our structures provide insight into agonist selectivity, ligand recognition, receptor activation, and G protein coupling. Our results provide a structural template for further improving IP-targeting drugs to reduce off-target activation of prostanoid receptors and adverse effects.
A multifaceted investigation of lactococcal strain diversity in undefined mesophilic starter cultures
Authors: White Kelsey , Eraclio Giovanni , McDonnell Brian , Bottacini Francesca , Lugli Gabriele Andrea , Ventura Marco , Volontè Federica , Dal Bello Fabio , Mahony Jennifer , van Sinderen Douwe
Published: February 2024

This study reports on the development of a combined culture-based analysis and metagenomics approach to evaluate the composition of two undefined mesophilic starter cultures. In addition, a novel qPCR-based genotype detection assay, capable of discerning nine distinct lactococcal genotypes (based on lactococcal cell wall polysaccharide biosynthesis gene clusters), was used to monitor compositional changes in an undefined starter culture following phage attack. These analytical approaches facilitate a multifaceted assessment of starter culture compositional stability during milk fermentation, which has become an important QC aspect due to the increasing demand for consistent and high-quality dairy products.
Lymphocytic choriomeningitis arenavirus requires cellular COPI and AP-4 complexes for efficient virion production
Authors: Byford Owen , Shaw Amelia B. , Tse Hiu Nam , Todd Eleanor J. A. A. , Álvarez-Rodríguez Beatriz , Hewson Roger , Fontana Juan , Barr John N.
Published: February 2024

Lymphocytic choriomeningitis virus (LCMV) is a bisegmented negative-sense RNA virus classified within the
Arenaviridae
family of the
Bunyavirales
order. LCMV is associated with fatal disease in immunocompromized populations, and as the prototypical arenavirus, acts as a model for the many serious human pathogens within this group. Here, we examined the dependence of LCMV multiplication on cellular trafficking components using a recombinant LCMV expressing enhanced green fluorescent protein in conjunction with a curated siRNA library. The screen revealed a requirement for subunits of both the coat protein 1 (COPI) coatomer and adapter protein 4 (AP-4) complexes. By rescuing a recombinant LCMV harboring a FLAG-tagged glycoprotein (GP-1) envelope spike (rLCMV-GP1-FLAG), we showed infection resulted in marked co-localization of individual COPI and AP-4 components with both LCMV nucleoprotein (NP) and GP-1, consistent with their involvement in viral processes. To further investigate the role of both COPI and AP-4 complexes during LCMV infection, we utilized the ARF-I inhibitor brefeldin A (BFA) that prevents complex formation. Within a single 12-h cycle of virus multiplication, BFA pre-treatment caused no significant change in LCMV-specific RNA synthesis, alongside no significant change in LCMV NP expression, as measured by BFA time-of-addition experiments. In contrast, BFA addition resulted in a significant drop in released virus titers, approaching 50-fold over the same 12-h period, rising to over 600-fold over 24 h. Taken together, these findings suggest COPI and AP-4 complexes are important host cell factors required for the formation and release of infectious LCMV.

IMPORTANCE

Arenaviruses are rodent-borne, segmented, negative-sense RNA viruses, with several members responsible for fatal human disease, with the prototypic member lymphocytic choriomeningitis virus (LCMV) being under-recognised as a pathogen capable of inflicting neurological infections with fatal outcome. A detailed understanding of how arenaviruses subvert host cell processes to complete their multiplication cycle is incomplete. Here, using a combination of gene ablation and pharmacological inhibition techniques, we showed that host cellular COPI and AP-4 complexes, with native roles in cellular vesicular transport, were required for efficient LCMV growth. We further showed these complexes acted on late stages of the multiplication cycle, post-gene expression, with a significant impact on infectious virus egress. Collectively, our findings improve the understanding of arenaviruses host-pathogen interactions and reveal critical cellular trafficking pathways required during infection.
A single-point mutation in the rubella virus E1 glycoprotein promotes rescue of recombinant vesicular stomatitis virus
Authors: Das Pratyush Kumar , Gonzalez Paulina Alatriste , Jangra Rohit K. , Yin Peiqi , Kielian Margaret
Published: February 2024

Rubella virus (RuV) is an enveloped plus-sense RNA virus and a member of the
Rubivirus
genus. RuV infection in pregnant women can lead to miscarriage or an array of severe birth defects known as congenital rubella syndrome. Novel rubiviruses were recently discovered in various mammals, highlighting the spillover potential of other rubiviruses to humans. Many features of the rubivirus infection cycle remain unexplored. To promote the study of rubivirus biology, here, we generated replication-competent recombinant VSV-RuV (rVSV-RuV) encoding the RuV transmembrane glycoproteins E2 and E1. Sequencing of rVSV-RuV showed that the RuV glycoproteins acquired a single-point mutation W448R in the E1 transmembrane domain. The E1 W448R mutation did not detectably alter the intracellular expression, processing, glycosylation, colocalization, or dimerization of the E2 and E1 glycoproteins. Nonetheless, the mutation enhanced the incorporation of RuV E2/E1 into VSV particles, which bud from the plasma membrane rather than the RuV budding site in the Golgi. Neutralization by E1 antibodies, calcium dependence, and cell tropism were comparable between WT-RuV and either rVSV-RuV or RuV containing the E1 W448R mutation. However, the E1 W448R mutation strongly shifted the threshold for the acid pH-triggered virus fusion reaction, from pH 6.2 for the WT RuV to pH 5.5 for the mutant. These results suggest that the increased resistance of the mutant RuV E1 to acidic pH promotes the ability of viral envelope proteins to generate infectious rVSV and provide insights into the regulation of RuV fusion during virus entry and exit.

IMPORTANCE

Rubella virus (RuV) infection in pregnant women can cause miscarriage or severe fetal birth defects. While a highly effective vaccine has been developed, RuV cases are still a significant problem in areas with inadequate vaccine coverage. In addition, related viruses have recently been discovered in mammals, such as bats and mice, leading to concerns about potential virus spillover to humans. To facilitate studies of RuV biology, here, we generated and characterized a replication-competent vesicular stomatitis virus encoding the RuV glycoproteins (rVSV-RuV). Sequence analysis of rVSV-RuV identified a single-point mutation in the transmembrane region of the E1 glycoprotein. While the overall properties of rVSV-RuV are similar to those of WT-RuV, the mutation caused a marked shift in the pH dependence of virus membrane fusion. Together, our studies of rVSV-RuV and the identified W448R mutation expand our understanding of rubivirus biology and provide new tools for its study.
Telomere-to-telomere genome assembly of the aflatoxin biocontrol agent
Aspergillus flavus
isolate La3279 isolated from maize in Nigeria
Authors: Legan Andrew W. , Mehl Hillary L. , Wissotski Marina , Adhikari Bishwo N. , Callicott Kenneth A.
Published: February 2024

Here, we report the complete genome of the non-aflatoxigenic
Aspergillus flavus
isolate La3279, which is an active ingredient of the aflatoxin biocontrol product Aflasafe. The chromosome-scale assembly clarifies the deletion pattern in the aflatoxin biosynthesis gene cluster and corrects a misidentified assembly previously published for this isolate.
Complete genome sequences of mycobacteriophages Ageofdapage, Aubs, BABullseye, CheetoDust, ShaboiShabazz, and TomBrady
Authors: Bass Shelbie , Coates Danielle , Frasketi Nina , James Smeetha , Marella Vishnu , Pulla Riya , Stoecker Kyle , Tupurani Srichandra , Johnson Allison A.
Published: February 2024

We report genome sequences of six mycobacteriophages. Each virus was isolated from a soil sample and belongs to the siphovirus morphology. Genomes are 41,901–60,613 bp in length, contain between 62 and 103 protein-coding genes, with up to 40% of those genes having a predicted function.