bluuebunny/crossref_metadata_2025 huggingface dataset:
Perfusion management during cardiopulmonary bypass in a patient with high cardiac output due to arteriovenous malformations
Authors: Pregaldini Fabio , Makaloski Vladimir , Erdoes Gabor , Schoenhoff Florian S
Published: December 2023

We present a case of a 37-year-old woman diagnosed with Parkes-Weber syndrome characterized by high-flow arterio-venous malformations of the pelvic region with an estimated cardiac output of 7.2–8.5 l/min. Due to concomitant Marfan syndrome, the patient also presented an aortic root aneurysm needing surgical treatment under cardiopulmonary bypass. Concerns arose regarding the ability to maintain sufficient perfusion pressure during cardiopulmonary bypass due to the arterio-venous malformations. To address this, an intravascular balloon occlusion at the level of the aortic bifurcation was placed in order to limit arterial inflow into the arterio-venous malformations and achieve optimal perfusion pressure during cardiopulmonary bypass. The patient did not experience any complications and recovered completely after surgery.
On Being Tongue-Tied: Franchise, Fluency, and Precarity in Montaigne’s ‘De la vanité’
Authors: O’Sullivan Luke
Published: December 2023

Drawing attention to a key but overlooked moment in Montaigne’s ‘De la vanité’, this article interrogates the relationship between two aspects of the essayist’s ‘franchise’: his personal freedom and his frank, direct speech. It offers a reading that runs counter to Montaigne’s self-characterization as ‘le plus libre et moins endebté’ person he knows, underscoring the precarity of his ‘franchise’ and his anxieties surrounding it. In this context, ‘franchise’ is shown to be hemmed in by a cluster of obligations, even as the essayist seeks to escape them. In contrast to the critical interest in Montaigne’s reflections on free-thinkers and courageous speakers, including Socrates, Seneca and Cato the Younger, and complementing studies that have highlighted the motif of babble and loquacity in the Essais, this article focuses on Montaigne seeing himself in a frightful inversion of ‘franchise’: the looking glass of Lyncestes and the story of his death as a consequence of his disfluency. Reading ‘franchise’ in this light helps us to learn what Montaigne considered one of the first lessons worth learning: the difference between ‘liberté’ and ‘licence’.
A prospective cohort study of presenteeism and increased risk of unemployment among Japanese workers during the COVID-19 pandemic
Authors: Fujino Yoshihisa , Okawara Makoto , Hino Ayako , Muramatsu Keiji , Nagata Tomohisa , Tateishi Seiichiro , Tsuji Mayumi , Ogami Akira , Ishimaru Tomohiro ,   for the CORoNaWork project
Published: December 2023

Objectives: Presenteeism adversely affects workers’ quality of life, leading to further deterioration of their health and affecting their ability to continue working. Unemployment is one of the most serious consequences for workers experiencing presenteeism. A worker’s ability to work depends on the degree of mismatch between their health status and job demands and work factors. The COVID-19 pandemic has affected workers’ experiences of presenteeism as well as their employment status. We examined the association between presenteeism and risk of job resignations and unemployment among Japanese workers during the COVID-19 pandemic.

Methods: A prospective study of 27 036 internet monitors was conducted, starting in December 2020, with 18 560 (68.7%) participating in the follow-up by December 2021. The Work Functioning Impairment Scale (WFun) was used to measure the degree of work function impairment.

Results: The group with the highest WFun scores had higher odds ratios (ORs) for both retirement and unemployment for health reasons than the group with the lowest WFun scores. ORs were 2.99 (95% CI, 2.48-3.62; P < .001) and 1.82 (95% CI, 1.65-2.00; P < .001), respectively.

Conclusions: Workers with work functioning impairment are at increased risk of resignation or unemployment. Management strategies for workers with work functioning impairment are needed to reduce their disadvantages in employment.
A skin comet sign after a trip to the Gambia
Authors: Rodriguez-Valero Natalia , Sarasola Balerdi Leire , Vera Isabel , de Alba Teresa , Saloni Meritxell , Camprubí-Ferrer Daniel
Published: December 2023

A comet-like skin lesion, observed post-travel to Western Africa, was diagnosed as a Pyemotes spp.-related condition, coincidentally following the reading of an old, dusty book.
Using Bayesian phylogenetics to infer manuscript transmission history
Authors: McCollum Joey , Turnbull Robert
Published: December 2023

Bayesian phylogenetic methods offer various models that would be especially suitable in the reconstruction of textual traditions, but text-critical applications of phylogenetics to date have generally not taken advantage of these features. In this article, we offer a way forward for text-critical phylogenetics. On the side of theory, we highlight multiple Bayesian phylogenetic models and discuss their relevance to textual criticism. More practically, we show how TEI XML collations of textual traditions can be encoded to facilitate robust analyses using these models in BEAST 2, with the teiphy Python package mediating the conversion from TEI XML to BEAST XML. Finally, we give a proof of concept for this approach, showing that the results of BEAST 2 analyses of a sample collation of the Epistle to the Ephesians under different clock models cohere with established findings on the textual tradition of this work.
Spin effect on redox acceleration and regioselectivity in Fe-catalyzed alkyne hydrosilylation
Authors: He Peng , Hu Meng-Yang , Li Jin-Hong , Qiao Tian-Zhang , Lu Yi-Lin , Zhu Shou-Fei
Published: December 2023

Iron catalysts are ideal transition metal catalysts because of the Earths abundant, cheap, biocompatible features of iron salts. Iron catalysts often have unique open-shell structures that easily undergo spin crossover in chemical transformations, a feature rarely found in noble metal catalysts. Unfortunately, little is known currently about how the open-shell structure and spin crossover affect the reactivity and selectivity of iron catalysts, which makes the development of iron catalysts a low efficient trial-and-error program. In this paper, a combination of experiments and theoretical calculations revealed that the iron-catalyzed hydrosilylation of alkynes is typical spin-crossover catalysis. Deep insight into the electronic structures of a set of well-defined open-shell active formal Fe(0) catalysts revealed that the spin-delocalization between the iron center and the 1,10-phenanthroline ligand effectively regulates the iron center's spin and oxidation state to meet the opposite electrostatic requirements of oxidative addition and reductive elimination, respectively, and the spin crossover is essential for this electron transfer process. The triplet transition state was essential for achieving high regioselectivity through tuning the nonbonding interactions. These findings provide an important reference for understanding the effect of catalyst spin state on reaction. It is inspiring for the development of iron catalysts and other Earth-abundant metal catalysts, especially from the point of view of ligand development.
Machine learning reveals that climate, geography, and cultural drift all predict bird song variation in coastal Zonotrichia leucophrys
Authors: Yang Jiaying , Carstens Bryan C , Provost Kaiya L
Published: December 2023

Previous work has demonstrated that there is extensive variation in the songs of White-crowned Sparrow (Zonotrichia leucophrys) throughout the species range, including between neighboring (and genetically distinct) subspecies Z. l. nuttalli and Z. l. pugetensis. Using a machine learning approach to bioacoustic analysis, we demonstrate that variation in song is correlated with year of recording (representing cultural drift), geographic distance, and climatic differences, but the response is subspecies- and season-specific. Automated machine learning methods of bird song annotation can process large datasets more efficiently, allowing us to examine 1,913 recordings across ~60 years. We utilize a recently published artificial neural network to automatically annotate White-crowned Sparrow vocalizations. By analyzing differences in syllable usage and composition, we recapitulate the known pattern where Z. l. nuttalli and Z. l. pugetensis have significantly different songs. Our results are consistent with the interpretation that these differences are caused by the changes in characteristics of syllables in the White-crowned Sparrow repertoire. This supports the hypothesis that the evolution of vocalization behavior is affected by the environment, in addition to population structure.
Social Movements
Authors: Chua Lynette J.
Published: December 2023

Although social movements and constitutional law are closely connected, their relationship tends to be overlooked in Asian constitutional law scholarship. Drawing from the socio-legal subfield of law and social movements, this chapter highlights the significance of studying social movements and their relationship to constitutional law in Asia. Because Asian jurisdictions are diverse, running the gamut from liberal democracies to various shades of illiberalism, this chapter does not emphasize any shared characteristics among social movements in the region. Rather, it considers social movement emergence, strategies and tactics, and both litigation and non-litigation outcomes in its examination of the relationship between social movements and constitutional law. It concludes with lessons from the socio-legal study of law and social movements, as well as from legal scholarship that has been influenced by this field, to offer suggestions on how Asian constitutional law scholars could approach the study of movement-constitution dynamics.
Psychology in Mathematics Education
Authors: Jones Ryan Seth , Lovett Jennifer , Fletcher Samantha , Heath Amanda Lake
Published: December 2023

This chapter explores the influence of psychology on Mathematics Education research, which is motivated by a desire to improve mathematical thinking and learning and coordinated between mathematics, psychologists, and educators. It explains how psychological perspectives are widely influential across research programs, especially depending on the age of the participants in the context. Moreover, the perspective ranges between diverse theoretical orientations from sociology, anthropology, economics, and many other philosophies. Mathematics Education researchers employ a diverse array of theoretical and methodological tools and often conduct research with different goals in mind. The chapter then highlights the importance of coordinating diverse perspectives for the future of Mathematics Education.
Precision medicine in inflammatory bowel disease
Authors: Zeng Zhen , Jiang Mingshan , Li Xi , Yuan Jing , Zhang Hu
Published: December 2023

Inflammatory bowel disease (IBD) is an incurable disease characterized by remission-relapse cycles throughout its course. Both Crohn's disease (CD) and ulcerative colitis (UC), the two main forms of IBD, exhibit tendency to develop complications and substantial heterogeneity in terms of frequency and severity of relapse, thus posing great challenges to the clinical management for IBD. Current treatment strategies are effective in different ways in induction and maintenance therapies for IBD. Recent advances in studies of genetics, pharmacogenetics, proteomics and microbiome provide a strong driving force for identifying molecular markers of prognosis and treatment response, which should help clinicians manage IBD patients more effectively, and then, improve clinical outcomes and reduce treatment costs of patients. In this review, we summarize and discuss precision medicine in IBD, focusing on predictive markers of disease course and treatment response, and monitoring indices during therapeutic drug monitoring.
Non-alcoholic fatty liver disease and risk of cardiovascular diseases: clinical association, pathophysiological mechanisms, and management
Authors: Yang Rong , Fan Jian-Gao
Published: December 2023

Non-alcoholic fatty liver disease (NAFLD) is a fatty liver disease associated with metabolic dysfunction in genetically susceptible individuals due to over-nutrition and lack of exercise. With the prevalence of obesity, metabolic syndrome, and type 2 diabetes mellitus, NAFLD has become the most common cause of chronic liver disease worldwide. NAFLD shares many risk factors with cardiovascular diseases (CVDs). NAFLD is associated with increased risk of major cardiovascular events and other cardiac complications even after adjustment for traditional cardiovascular risk factors. The primary pathology of NAFLD is within the liver, but the most common cause of deaths in patients with NAFLD is CVDs. This review summarizes the epidemiological evidence for the association between NAFLD and CVD risk and the pathophysiological mechanisms underlying this association. Current treatment strategies for NAFLD and their potential impact on CVD risk are also discussed.
Forearm Granular Cell Tumor: A Rare Entity
Authors: Mansour Walaa Anis , El Saloussy Yasmeen , Wahdan Wessam
Published: December 2023

Granular cell tumors are uncommon benign masses. They occur rarely and are usually solitary, nontender lesions, with a tendency to occur in the head and neck region and a predilection for the tongue. A malignant variant is even less common. To date, its origin remains uncertain. We report the case of a 19-year-old Egyptian man who presented to the Kasr eini Plastic Surgery Clinic with a swelling on the posterior aspect of his right forearm. After surgical excision and histopathological examination, it was found to be a granular cell tumor. This finding was of interest because of the rarity of the neoplasm in general, but in particular because of the scarcity of its occurrence in this anatomic location and the patient’s sex, and age group.
Potential of serious games as a competency assessment tool for acute care nurses on the blood transfusion procedure
Authors: Rajasegeran Darshini Devi , Liu Kai , Sheng Yanyan , Loh Christian Sebastian , Choh Andrea Chau Lin , Teo Kai Yunn , Fan Peijin Esther Monica , Tan Min Yi , Aloweni Fazila , Ang Shin Yuh
Published: December 2023

Background:

Blood transfusion is a life-saving treatment that requires comprehensive knowledge and compliance to safety, administration, and management of blood transfusion process. It is a core competency for a registered nurse. Competency assessments are annually conducted as regulatory requirement and for quality assurance within our institution. Prior to using serious games, competency assessment involved an online learning module followed by a face-to-face assessment. This had limitations such as such as limited opportunities, potential lack of standardisation, time, and resources.

Aim:

The aim of this study was to assess whether serious game for blood transfusion administration could be a valid and reliable nursing competency assessment tool through capturing and analysis of in-game empirical data.

Methods:

The nursing department from Singapore General Hospital (SGH) developed a serious game for blood transfusion administration. The game modules were developed to match the actual procedure with established learning objectives at each stage. The game’s content validity was assessed by four external subject-matter-experts. Gameplay data of 1093 nurses were tested for construct validity, internal-consistency reliability, and criterion validity of the game.

Results:

The item-level content validity index (I-CVI) ranged between 0.75 and 1, while the average of the I-CVI scores for all items on the scale (S-CVI/Ave) was 0.99. Six factors and 82 game actions were obtained using principle factor analysis. Most game actions had a communality value (h2) above 0.5. The Inter-factor correlations between the six factors ranged from 0.2 to 0.45. Internal-consistency reliability estimates (α) (together with their 95% CIs) for the stages were greater than 0.75, with an overall of 0.96 for the 82 game actions. Linear association between each predictor and the criterion were below 0.25.

Conclusion:

Based on the empirical data collated, we conclude that the serious game may be a valid competency assessment tool for nurses in SGH. For future work, we propose to conduct the blood transfusion serious game in other hospitals to further support its validity and reliability as a competency tool for multi-step complex procedural clinical skills.
Bromocriptine: does this drug of Parkinson’s disease have a role in managing cardiovascular diseases?
Authors: Kutikuppala Lakshmi Venkata Simhachalam , Sharma Sushil , Chavan Madhavrao , Rangari Gaurav , Misra Arup Kumar , Innamuri Sai Ram , Vijayakumar Tejus , Varshitha Golla
Published: December 2023

Cardiovascular disease (CVD) is the most common cause of morbidity and mortality worldwide. Bromocriptine is a partial antagonist for D1 dopamine receptors while also serving as a selective agonist on D2 dopamine receptors as a dopamine receptor agonist. Apart from prolactin inhibiting action, bromocriptine has some beneficial effects on the blood pressure, plasma norepinephrine levels and vascular resistance. Dopamine D2 receptor activation of bromocriptine is associated with the antihypertensive effect, which lowers blood pressure via inhibiting sympathetic nerve activity and Na/K ATPase activity. Plasma levels of the pro-inflammatory cytokines such as interleukin (IL)-1B and IL-18, chemokine CCL2/ MCP-1/, and the pro-inflammatory hormone prolactin, all of which are elevated and linked to accelerated cardiometabolic illness, were decreased because of bromocriptine therapy. The most common side effects of Bromocriptine use are dizziness, nausea, headache, vomiting and hypotension. Bromocriptine is mainly contraindicated in patients with syncope with hypotension, psychosis, and type I diabetes mellitus. The authors suggest that developing therapies directed to increase D2 receptor expression and function by drugs like Bromocriptine can provide practical and novelistic approaches to prevent and manage myocardial and renal injury in the cardiovascular disease patients.
Experiences of Intensive Care Unit Nurses in Caring for Brain-Dead Donors
Authors: Son Minseo , Kim Nageong
Published: December 2023

Organ donation after brain death is an alternative to living organ donation, which has various risks and is a means of addressing organ supply shortages. In South Korea, primarily, the organ donation decision is made by the brain-dead donor's family under the guidance of medical staff. Intensive care unit nurses, who are consistently present with patients, can significantly influence families' decision-making process. Hence, nurses' experiences of caring for brain-dead donors should be explored to obtain detailed explanations of the related complex social phenomena. This qualitative study aimed to understand the structure and nature of nurses' experiences using Colaizzi's phenomenological method. Data were collected from 10 intensive care unit nurses from a hospital-based organ procurement organization between June 27 and September 10, 2022. Twelve themes and 5 components were identified from participants' interviews, including “nursing with regret,” “enduring agony from repeatedly caring for deceased organ donors,” “lack of a support system,” “deep emotional pain and scarring left after care,” and “balancing emotions.” It is necessary to clarify the required nursing interventions and role of nurses in intensive care units who care for brain-dead donors and develop specific guidelines to assist them in their work.
SMARCA4/BRG1-deficient Uterine Neoplasm With Hybrid Adenosarcoma and Carcinoma Features: Expanding the Molecular-morphologic Spectrum of SMARCA4-driven Gynecologic Malignancies
Authors: Wei Christina H. , Sadimin Evita , Agulnik Mark , Yost Susan E. , Longacre Teri A. , Fadare Oluwole
Published: December 2023

SMARCA4 gene encodes BRG1, a member of the SWItch/sucrose non-fermentable protein family involved in epigenetic transcriptional regulation of important cellular processes. In the uterine corpus, SMARCA4/BRG1 deficiency is associated with a novel class of undifferentiated uterine sarcomas, characterized by younger age onset, rhabdoid histology, focal phyllodiform architecture, high-risk pathologic findings, and dismal prognosis. Herein, we report a case of a 34-year-old Asian woman with a SMARCA4/BRG1-deficient uterine tumor fulfilling the clinicopathologic features of an undifferentiated uterine sarcoma. However, the tumor exhibited several unique features that have not been previously emphasized, including (1) conspicuous phyllodiform architecture recapitulating conventional adenosarcoma, (2) rhabdoid tumor cells forming cords and keratin-positive cohesive epithelial islands, and (3) cooccurrence with a spatially distinct and discrete endometrial complex atypical hyperplasia from the rest of the proliferation. By immunohistochemistry, the tumor cells were diffusely positive for synaptophysin, whereas BRG1 was lost. Pertinent molecular findings included frameshift mutations in the SMARCA4 gene, mutations in histone modification and chromatin remodeling genes, including KMT2C, ARID1B, KAT6A, and NCOR1, and mutations in Wnt signaling involving APC and CTNNB1. Copy number gain in MDM2 and CDK4 were also identified. The tumor mutation burden was intermediate (6.8/MB) and it was microsatellite stable. On balance, our case exhibited morphologic and molecular features that overlap with (1) an undifferentiated uterine sarcoma, (2) an adenosarcoma with sarcomatous overgrowth, and (3) a mixed adenosarcoma and undifferentiated endometrial carcinoma. These hybrid features further expand the molecular-morphologic spectrum of SMARCA4/BRG1-deficient uterine neoplasms.
Preliminary view of the distribution and spread of the plasmid-mediated resistance genes in Glaesserella parasuis
Authors: Sun Huarun , Li Minghui , Bai Yilin , Sun Yawei , Zhu Chunling , Xia Xiaojing , Zhang Huihui , Luo Weiyu , Zhang Wei , Wen Yuliang , Bai Yueyu , Wang Lei , Hu Jianhe
Published: December 2023

Introduction. Various plasmid-mediated resistance genes have been reported in

Glaesserella parasuis

, but little is known about their global distribution features, evolution pattern and spread.

Gap Statement. The potential mobilization mechanisms of resistance plasmids in

G. parasuis

have been poorly explored.

Aim. The aim of the study was to investigate the prevalence and diversity of plasmid-mediated resistance genes among

G. parasuis

isolates, and focus on the analysis of the features of the resistance plasmids from

G. parasuis

.

Method. The plasmids tested were sequenced using the Illumina HiSeq platform in conjunction with PCR and inverted PCR. The susceptibility of the host strains was determined by broth microdilution. The transfer of plasmids tested was conducted by electroporation. The sequence data were compared using bioinformatics tools and the data from our laboratory and the National Center for Biotechnology Information (NCBI) database.

Results. Nineteen plasmids were identified from our laboratory and these resistance plasmids were functional and transferable. Moreover, we clustered five types of genetic backbones of plasmids from

G. parasuis

and revealed the global distribution features of the plasmid-mediated resistance genes.

Conclusions. This is the first report of the coexistence of tet(H)-bearing type I plasmid and lnu(C)-bearing type II plasmid in one

G. parasuis

clinical isolate. In addition, this study provides the first view of the global distribution of plasmid-mediated resistance genes and classifies the plasmids in

G. parasuis

according to their backbone regions.
Monitoring for 5-aminosalicylate toxicity: prognostic model development and validation
Authors: Abhishek A , Nakafero Georgina , Grainge Matthew J , Card Tim , Taal Maarten W , Aithal Guruprasad P , Fox Christopher P , Mallen Christian D , Stevenson Matthew D , Riley Richard D
Published: December 2023

Background and aim

To develop and validate a prognostic model for risk-stratified monitoring of 5-aminosalicylate (5-ASA) toxicity.

Methods

This nationwide retrospective cohort study used data from the Clinical Practice Research Datalink (CPRD) Aurum and Gold for model development and validation respectively. It included adults newly diagnosed with inflammatory bowel disease (IBD) and established on 5-ASAs between 01/01/2007 and 31/12/2019. 5-ASA discontinuation with abnormal monitoring blood test result was the outcome of interest. Patients prescribed 5-ASAs for ≥6 months i.e., established on treatment, were followed-up for up to five years. Penalised Cox-regression was used to develop the risk equation. Model performance was assessed in terms of calibration and discrimination. Statistical analysis was performed using STATA (StataCorp LLC).

Results

14,109 and 7,523 participants formed the development and validation cohorts with 401 and 243 events respectively. 185, 172, and 64 discontinuations were due to cytopenia, elevated creatinine and elevated liver enzymes respectively in the derivation cohort. Hazardous alcohol intake, chronic kidney disease, thiopurine use, and blood test abnormalities before follow-up were strong prognostic factors. The optimism adjusted R2Din development data was 0.08. The calibration slope and Royston D statistic (95% Confidence Interval) in validation cohort were 0.90 (0.61-1.19) and 0.57 (0.37-0.77) respectively.

Conclusion

This prognostic model utilises information available during routine clinical care and can be used to inform decisions on the interval between monitoring blood-tests. The results of this study ought to be considered by guideline writing groups to risk-stratify blood test monitoring during established 5-ASA treatment.

What is already known?

Renal, hepatic and blood toxicity are uncommon during long-term 5-aminosalicylate (5-ASA) treatment.

There are no mechanisms to predict the risk of these toxicities during established treatment that may be used to risk stratify blood-test monitoring.

What this study adds?

Using a large national dataset originated during routine care, this study developed a prognostic model that discriminated patients at varying risk of 5-ASA toxicity during established treatment with good performance characteristics validated.

Most patients were at low-risk of toxicity due to 5-ASAs and could continue with annual monitoring blood-tests while others at high risk may require more frequent monitoring.

This prognostic model can be used to make an informed decision on the interval between monitoring blood tests and the findings ought to be considered by guideline writing groups to bring about equitable and sustainable change in clinical practice.
Comparative Analysis of the Duodenojejunal Microbiome with the oral and fecal microbiome unveils its role in Human Severe Obesity
Authors: Steinbach Emilie , Belda Eugeni , Alili Rohia , Adriouch Solia ,   Jejunal Luminal and Colonic Mucosa-Associated Microbiota in Metabolic Diseases (Je/Col-MiMe) Group, Chassaing Benoit , Le Roy Tiphaine , Clement Karine
Published: December 2023

The intestinal microbiota is recognized as an important player in the development and maintenance of obesity. Most studies focus on faecal microbiota because of its accessibility. However, the small intestine is a major site for nutrient sensing and absorption and few studies have examined the composition and function of the microbiota in this segment of the digestive tract.

We conducted a clinical research project on 30 age- and sex-matched participants with (N=15) and without (N=15) obesity. Duodenojejunal fluid was obtained by aspiration during fibroscopy. Phenotyping included clinical variables related to metabolic status, lifestyle and psychosocial factors using validated questionnaires. Metagenomic analyses of the oral, duodenojejunal and faecal microbiome, as well as metabolomic data from duodenojejunal fluid and faeces, were integrated with clinical and lifestyle data.

The results show associations between duodenojejunal microbiota and lifestyle as well as clinical phenotypes. These associations had larger effect sizes than the associations between these variables and faecal microbiota. We also observed that the duodenojejunal microbiota of obese patients had a higher diversity. In addition, we observed differences in the abundance of several species of the duodenojejunal microbiota between control individuals and patients suffering from obesity.

In conclusion, our results support the relevance of studying the role of the small intestinal microbiota in the development of metabolic diseases.
Reward processing in young people with self-harm behaviour
Authors: Yavuz Emre , Rodrigues Rachel , Sanchez Ana Pascual , Lingford-Hughes Anne , Simplicio Martina Di
Published: December 2023

Twenty percent of young people report a lifetime presence of self-harm (SH) behaviour, associated with negative health and functional outcomes. Understanding the underlying cognitive mechanisms is needed to develop targeted early interventions. Reward processing biases may underlie SH, aligning with accounts of the behaviour acquiring “addictive” characteristics. However, the specific nature of such biases remains unclear, particularly its relationship with negative affect (NA) that frequently triggers SH. In Study 1, we compared young people (aged 16-25) with SH to a group with NA but no SH history and a healthy control group on performance of a novel Incentive Delay Task (IDT), with SH-related (SH trials), positive social (social trials) or monetary images (money trials) as stimuli. In Study 2, a different sample of SH and HC participants completed the same IDT following NA induction via an online Trier Social Stress Test. For both studies, we hypothesised faster and more correct responses in the SH group than control groups on SH trials. Contradicting our hypothesis, there were no significant between-group differences in IDT performance on SH, social and money trials in either study. Certain SH characteristics (positive reinforcement, SH mental imagery, urge) were significantly correlated with better performance on SH trials in SH participants. Thus, broadly SH behaviour may not be underpinned by motivational biases towards SH-related cues or naturalistic rewards. Future studies should clarify whether incentivisation of SH-related cues instead explains individual differences in SH behaviour and its relation with treatment and prognosis.
Neuropathology-based GWAS for Alzheimer’s disease reveals novel susceptibility loci and highlights sex-specific pathways
Authors: Jin Yin , Topaloudi Apostolia , Shekhar Sudhanshu , Scott Alicia Nicole , Colon Bryce David , Drineas Petros , Rochet Chris , Paschou Peristera
Published: December 2023

Dementia refers to an umbrella phenotype of many different underlying pathologies with Alzheimer’s disease (AD) being the most common type. While Genome-wide Association Studies (GWAS) of clinically defined AD have identified multiple AD susceptibility variants, a significant portion of the heritability remains unexplained highlighting the phenotypic and genetic heterogeneity of the clinically defined entity. Furthermore, despite women’s increased susceptibility to dementia there is a lack of sex-specific genetic studies and understanding of sex-specific background for the disorder. Here, we aim to tackle the heterogeneity of AD by specifically concentrating on neuropathological features which are the gold standard for diagnosis and pursuing sex-specific analysis. We bring together 13 different genomic and neuropathology datasets (6,960 individuals) and we integrate our GWAS findings with transcriptomic and proteomic data (ROSMAP and Mayo studies) aiming to also identify in vivo biomarkers for AD progression. We uncover novel genetic associations to AD neuropathology, including BIN1, OPCML, and CDH4. Our sex-specific analysis points to a role for BIN1 specifically in women as well as novel AD loci including QRFPR and SGCZ. Tissue-specific associations in females, particularly in the ovary issue, suggest a connection between sex hormones and AD. Finally, we pursue the identification of in-vivo biomarkers associated with AD neuropathology, with a goal to offer insights into disease progression and potential therapeutic targets. Our findings contribute to unraveling the molecular basis of AD, emphasizing the importance of sex-specific analyses and multi-omics approaches. Further research is needed to validate and explore the clinical utility of these findings.
Global associations of macronutrient supply and asthma disease burden
Authors: Ni Duan , Senior Alistair M. , Raubenheimer David , Simpson Stephen J. , Macia Laurence , Nanan Ralph
Published: December 2023

Objectives

Global age-standardized prevalence of asthma has decreased over time, in parallel with which, the gross domestic product (GDP) per capita and nutritional landscapes also changed at a global level. Both socioeconomic status and nutritional factors are critical confounder for asthma, but most studies so far neglected to interrogate their correlations and interactions comprehensively. Hence, we aim to systematically investigate the relationship between nutrient supply, a good proxy of food environment, socioeconomic status and asthma disease burden at a global level over time.

Methods

Asthma disease burden, macronutrient (protein, carbohydrate and fat) supply and GDP data covering more than 150 countries around the globe from 1990 to 2018 was collated. Various multi-response generalized additive mixed models (GAMMs) were used to analyze the effects of macronutrient supplies and GDP over time on asthma disease burden.

Results

A model considering the interactions between macronutrient supplies and GDP, with an additive effect of time was favoured. Modelling results showed that carbohydrate supply was most strongly associated with increase of asthma disease burden, while fat supply had an opposite effect, and protein supply conferred less influences.

Conclusions

Globally, carbohydrate supply seems to play a driving role for asthma disease burden while fat supply might be the opposite. This is supported by previous studies about the amelioration of established asthma by ketogenic diet and might be linked to the diet quality. Further in-depth studies are warranted, which will be critical for future clinical research and practice and public health intervention.
Long-Term Outcomes of SARS-CoV-2 Variants and Other Respiratory Infections: Evidence from the Virus Watch Prospective Cohort in England
Authors: Beale Sarah , Yavlinsky Alexei , Fong Wing Lam Erica , Nguyen Vincent G , Kovar Jana , Vos Theo , Hansen Sarah Wulf , Hayward Andrew C , Abubakar Ibrahim , Aldridge Robert W
Published: December 2023

Background

Given the considerable prevalence of long-term sequelae following SARS-CoV-2 infection, understanding pathogen-related factors that influence long-term outcomes is warranted. We aimed to compare the likelihood of long-term symptoms for SARS-CoV-2 variants, other acute respiratory infections (ARIs) and non-infected individuals.

Method

Data were from 5,630 individuals participating in Virus Watch, a prospective community cohort study of SARS-CoV-2 epidemiology in England. We used logistic regression to compare the predicted probability of developing long-term symptoms (>2 months duration) during different variant dominance periods according to infection status (SARS-CoV-2, other ARI, or no infection), adjusting for confounding by demographic and clinical factors and vaccination status.

Results

Predicted probability of long-term sequelae was greater following SARS-CoV-2 infection during the Wild Type (adjusted predicted probability (PP) 0.28, 95% confidence interval (CI) =0.14-0.43), Alpha (PP= 0.28, 95% CI =0.14-0.42), Delta (PP= 0.34, 95% CI=0.25-0.43) and Omicron BA.1 periods (PP= 0.27, 95% CI =0.22-0.33) compared to later Omicron sub-variants (PP range from 0.11, 95% CI 0.08-0.15 to 0.14, 95% CI 0.10-0.18). While differences between SARS-CoV-2 and other ARIs (PP range 0.08, 95% CI 0.04-0.11 to 0.23, 95% CI 0.18-0.28) varied by period, estimates for long-term symptoms following both infection types substantially exceeded those for non-infected participants (PP range 0.01, 95% CI 0.00,0.02 to 0.03, 95% CI 0.01-0.06) across all variant periods.

Conclusions

Between-variant differences influenced the likelihood of post-infection sequelae for SARS-CoV-2, with lower predicted probabilities for recent Omicron sub-variants similar to those for other contemporaneous ARIs. Both SARS-CoV-2 and other ARIs were associated with long-term symptom development, and further aetiological investigation including between-pathogen comparison is recommended.
Investigation of choroid plexus variability in schizophrenia-spectrum disorders – insights from a multimodal study
Authors: Yakimov Vladislav , Moussiopoulou Joanna , Roell Lukas , Kallweit Marcel S. , Boudriot Emanuel , Mortazavi Matin , Papiol Sergi , Krčmář Lenka , Campana Mattia , Schulte Eva C. , Glaichenhaus Nicolas , Martinuzzi Emanuela , Halstead Sean , Warren Nicola , Siskind Dan , Maurus Isabel , Hasan Alkomiet , Falkai Peter , Schmitt Andrea , Raabe Florian ,   CDP Working Group, Keeser Daniel , Wagner Elias
Published: December 2023

Background and Hypothesis

Previous studies have suggested that choroid plexus (ChP) enlargement occurs in individuals with schizophrenia-spectrum disorders (SSD) and is associated with peripheral inflammation. However, it is unclear whether such an enlargement delineates a biologically defined subgroup of SSD. Moreover, it remains elusive how ChP is linked to brain regions, associated with peripheral inflammation in SSD.

Study Design

A cross-sectional cohort of 132 individuals with SSD and 107 age-matched healthy controls (HC) underwent magnetic resonance imaging (MRI) of the brain and clinical phenotyping to investigate the ChP and associated regions. Case-control comparison of ChP volumes was conducted and structural variance was analysed by employing the variability ratio (VR). K-means clustering analysis was used to identify subgroups with distinct patterns of the ventricular system and the clusters were compared in terms of demographic, clinical and immunological measures. The relationship between ChP volumes and brain regions, previously associated with peripheral inflammation, was investigated.

Study Results

We could not find a significant enlargement of the ChP in SSD compared to HC but detected an increased VR of ChP and lateral ventricle volumes. Based on these regions we identified 3 clusters with differences in age, symbol coding test scores and possibly inflammatory markers. Larger ChP volume was associated with higher volumes of hippocampus, putamen, and thalamus in SSD, but not in HC.

Conclusions

This study suggests that ChP variability, but not mean volume, is increased in individuals with SSD, compared to HC. Larger ChP volumes in SSD were associated with higher volumes of regions, previously associated with peripheral inflammation.
Ghrelin is associated with an elevated mood after an overnight fast in depression
Authors: Fahed Rauda , Schulz Corinna , Klaus Johannes , Ellinger Sabine , Walter Martin , Kroemer Nils B.
Published: December 2023

Background

Major depressive disorder (MDD) comprises subtypes with distinct symptom profiles. For example, patients with melancholic and atypical MDD differ in the direction of appetite and body weight changes as well as mood reactivity. Despite reported links to altered energy metabolism, the role of circulating neuropeptides from the gut in modulating such symptoms remains largely elusive.

Methods

We collected data from 103 participants, including 51 patients with MDD and 52 healthy control participants (HCP). After an overnight fast, we measured blood levels of (acyl and des-acyl) ghrelin and participants reported their current metabolic and mood states using visual analog scales (VAS). Furthermore, they completed symptom-related questionnaires (i.e., STAI-T).

Results

Patients with atypical versus melancholic MDD reported less negative affect (p= .025). Higher levels of acyl ghrelin (corrected for BMI) were associated with improved mood (p= .012), specifically in patients with MDD. These associations of ghrelin were not mood-item specific and exceeded correlations with trait markers of negative affectivity. In contrast to associations with mood state, higher levels of ghrelin were not associated with increased hunger per se or changes in appetite in patients with MDD.

Limitations

The study is limited by the cross-sectional design without an intervention.

Conclusions

Our results reveal potentially mood-enhancing effects of ghrelin in fasting individuals that exceed associations with metabolic state ratings. These associations with circulating neuropeptides might help explain anti-depressive effects of fasting interventions and could complement conventional treatments in patients with melancholic MDD.

Graphical abstract
Regulatory networks of KRAB zinc finger genes and transposable elements changed during human brain evolution and disease
Authors: Chen Yao-Chung , Maupas Arnaud , Nowick Katja
Published: December 2023

Evidence indicates that transposable elements (TEs) can contribute to the evolution of new traits, despite often being considered deleterious. In vertebrates, some KRAB-ZNF proteins repress TEs, offering genomic protection. Notably, KRAB-ZNF genes evolve rapidly and exhibit diverse expression patterns in primate brains, where TEs remain active. This prompts questions about their interactions in primate brains and potential roles in human brain evolution and disease. For a systematic comparative analysis of TE interactions with other genes, we developed the tool TEKRABber, and focused on strong and experimentally validated cases. Our bipartite network analysis revealed significantly more interactions between KRAB-ZNF genes and TEs in humans than in other primates, especially with recently evolved, i.e. Simiiformes specific, TEs. Notably, ZNF528, under positive selection in humans, shows numerous human-specific TE interactions. Most negative interactions in our network, indicative of repression by KRAB-ZNF proteins, entail Alu TEs, while links to other TEs are generally positive. In Alzheimer’s patients, a subnetwork involving 21 interactions with an Alu module appears diminished or lost. Our findings suggest that KRAB-ZNF and TE interactions vary across TE families, have increased throughout human evolution, and may influence susceptibility to Alzheimer’s disease.

Graphical Abstract

Figure 1.
A Functional Schizophrenia-associated genetic variant near theTSNARE1andADGRB1genes
Authors: Wahbeh Marah H. , Boyd Rachel J. , Yovo Christian , Rike Bailey , McCallion Andrew S. , Avramopoulos Dimitrios
Published: December 2023

Recent collaborative genome wide association studies (GWAS) have identified >200 independent loci contributing to risk for schizophrenia (SCZ). The genes closest to these loci have diverse functions, supporting the potential involvement of multiple relevant biological processes; yet there is no direct evidence that individual variants are functional or directly linked to specific genes. Nevertheless, overlap with certain epigenetic marks suggest that most GWAS-implicated variants are regulatory. Based on the strength of association with SCZ and the presence of regulatory epigenetic marks, we chose one such variant nearTSNARE1andADGRB1, rs4129585, to test for functional potential and assay differences that may drive the pathogenicity of the risk allele. We observed that the variant-containing sequence drives reporter expression in relevant neuronal populations in zebrafish. Next, we introduced each allele into human induced pluripotent cells and differentiated 4 isogenic clones homozygous for the risk allele and 5 clones homozygous for the non-risk allele into neural precursor cells. Employing RNA-seq, we found that the two alleles yield significant transcriptional differences in the expression of 109 genes at FDR <0.05 and 259 genes at FDR <0.1. We demonstrate that these genes are highly interconnected in pathways enriched for synaptic proteins, axon guidance, and regulation of synapse assembly. Exploration of genes near rs4129585 suggests that this variant does not regulateTSNARE1transcripts, as previously thought, but may regulate the neighboringADGRB1, a regulator of synaptogenesis. Our results suggest that rs4129585 is a functional common variant that functions in specific pathways likely involved in SCZ risk.
Amyloid precursor protein induces reactive astrogliosis
Authors: Jauregui Gretsen Velezmoro , Vukić Dragana , Onyango Isaac G. , Arias Carlos , Novotný Jan S. , Texlová Kateřina , Wang Shanshan , Kovačovicova Kristina Locker , Polakova Natalie , Zelinkova Jana , Čarna Maria , Strašil Valentina Lacovich , Head Brian P. , Havas Daniel , Mistrik Martin , Zorec Robert , Verkhratsky Alexei , Keegan Liam , O’Connel Mary , Rissman Robert , Stokin Gorazd B.
Published: December 2023

We presentin vitroandin vivoevidence demonstrating that Amyloid Precursor Protein (APP) acts as an essential instigator of reactive astrogliosis. Cell-specific overexpression of APP in cultured astrocytes led to remodelling of the intermediate filament network, enhancement of cytokine production and activation of cellular programs centred around the interferon (IFN) pathway, all signs of reactive astrogliosis. Conversely, APP deletion in cultured astrocytes abrogated remodelling of the intermediate filament network and blunted expression of IFN stimulated gene (ISG) products in response to lipopolysaccharide (LPS). Following traumatic brain injury (TBI), mouse reactive astrocytes also exhibited an association between APP and IFN, while APP deletion curbed the increase in glial fibrillary acidic protein (GFAP) observed canonically in astrocytes in response to TBI. Thus, APP represents a molecular inducer and regulator of reactive astrogliosis.
HURP facilitates spindle assembly by stabilizing microtubules and working synergistically with TPX2
Authors: Valdez Venecia , Ma Meisheng , Gouveia Bernardo , Zhang Rui , Petry Sabine
Published: December 2023

In large vertebrate spindles, the majority of microtubules are formed via branching microtubule nucleation, whereby microtubules nucleate along the side of pre-existing microtubules. Hepatoma up-regulated protein (HURP) is a microtubule-associated protein that has been implicated in spindle assembly, but its mode of action is yet to be defined. In this study, we show that HURP is necessary for RanGTP-induced branching microtubule nucleation inXenopusegg extract. Specifically, HURP stabilizes the microtubule lattice to promote microtubule formation from γ- TuRC. This function is shifted to promote branching microtubule nucleation in the presence of TPX2, another branching-promoting factor, as HURP’s localization to microtubules is enhanced by TPX2 condensation. Lastly, we provide a structure of HURP on the microtubule lattice, revealing how HURP binding stabilizes the microtubule lattice. We propose a model in which HURP stabilizes microtubules during their formation, and TPX2 preferentially enriches HURP to microtubules to promote branching microtubule nucleation and thus spindle assembly.