bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrity games: an online teaching tool on academic integrity for undergraduate students
Authors: Goddiksen Mads Paludan , Allard Aurélien , Armond Anna Catharina Vieira , Clavien Christine , Loor Hillar , Schöpfer Céline , Varga Orsolya , Johansen Mikkel Willum 
Published: May 2024

AbstractIn this paper, we introduce Integrity Games (https://integgame.eu/) – a freely available, gamified online teaching tool on academic integrity. In addition, we present results from a randomized controlled experiment measuring the learning outcomes from playing Integrity Games.Integrity Games engages students in reflections on realistic and relevant academic integrity issues that lie in the grey zone between good practice and misconduct. Thereby, it aims to 1) motivate students to learn more about academic integrity, 2) increase their awareness of the grey-zone issues, and 3) increase their awareness of misconduct. To achieve these aims, the tool presents four gamified cases that lead students through an engaging narrative.The experiment to measure learning outcomes was conducted in three European countries, and included N = 257 participants from across natural science, social science and the humanities. We show that the participants enjoyed playing Integrity Games, and that it increased their sensitivity to grey-zone issues and misconduct. However, the increases identified were similar to those achieved by the participants in the control group reading a non-gamified text.We end by discussing the value of gamification in online academic integrity training in light of these results.
Quantifying the relative importance of biotic and abiotic factors in landscape-based models of stream fish distributions
Authors: Custer Christopher A. , Fischer Douglas P. , Smith Geoffrey , Henning Aaron , Schall Megan Kepler , Shank Matthew K. , Wertz Timothy A. , Wagner Tyler 
Published: May 2024

AbstractLotic fish species distributions are frequently predicted using remotely sensed habitat variables that characterize the adjacent landscape and serve as proxies for instream habitat. Recent advancements in statistical methodology, however, allow for leveraging fish assemblage data when predicting distributions. This is important because assemblage composition likely provides better information about instream habitat compared to landscape-derived metrics and therefore may improve predictions. To better understand the value of using multi-species fish data in species distribution modeling, we fit two conditional random fields (CRF) models to quantify the relative importance of fish assemblage co-occurrence, landscape-derived habitat variables, and interactions between these two predictor groups (i.e., effects of co-occurrence could be context-dependent) at over 1200 stream catchments in Pennsylvania, USA. We first compared predictive performance of CRF models against traditionally used single-species logistic regressions (generalized linear models; GLMs) and found that inclusion of fish assemblage data often improved predictive performance. The multi-species CRF models performed significantly better at predicting occurrence for 63% of species with an average percent increase in AUC of 25% compared to GLMs. Furthermore, the CRF identified species co-occurrences as more informative, and thus relatively more important, at predicting occurrence than the other effect types. The CRF also suggested that allowing these biotic effects to be context-dependent was important for predicting occurrence of many species. These findings illustrate the value of fish assemblage data for landscape-scale species distribution modeling and leveraging this information can improve predictions and inferences to help inform the management and conservation of freshwater fishes.
Correlation between Serum Levels of Nitric Oxide and Adropin and Erectile Dysfunction in Males with Nonalcoholic Fatty Liver Disease: An Observational Study
Authors: Ragab Ahmed , Fattah Ali M Abdel , Sayed Ahmed Reda , GamalEl Din Sameh Fayek , Mahmoud Hassan Shrouk Matrawy , Mohamed Aya Yaseen Mohamed , Hamed Mostafa Ahmed 
Published: May 2024

AbstractThe current study aimed to evaluate the serum levels of nitric oxide (NO) and adropin in males with non-alcoholic fatty liver disease (NAFLD) induced erectile dysfunction (ED) and NAFLD patients without ED and controls. The current study selected 165 participants from the hepatology department from November 2021 to November 2022. The patients were either suffering from NAFLD with normal liver functions or non-alcoholic steatohepatitis with abnormal liver functions. They were diagnosed by abdominal ultrasonography. Participants were evaluated using the validated Arabic version of the International Index of Erectile Function (ArIIEF-5), the Arabic form of the Generalized Anxiety Disorder-7 (GAD-7) questionnaire and the Patient Health Questionnaire-9 (PHQ-9). Noteworthy, there were significant positive correlations between ArIIEF-5 score, NO, adropin and total testosterone (r = 0.380, p = 0.001; r = 0.507, p =  < 0.001; r = 0.246, p = 0.038, respectively). Meanwhile, there were significant negative correlations between ArIIEF-5 score, creatinine, duration of the disease and scores of GAD-7 and PHQ-9 (r = -0.656, p =  < 0.001; r = -0.368, p = 0.002; r = -0.663, p =  < 0.001; r = -0.248, p = 0.037, respectively). Finally, a linear regression analysis revealed that GAD-7, creatinine, and adropin were the only strong independent predictors of ArIIEF-5, as the 95% confidence interval in the form of upper and lower bounds was -0.349, -0.843, p < 0.001, -6.507, -18.402, p < 0.001, 0.476, 0.117, and p 0.002, respectively. Impaired NO and adropin levels play a potential role in the development of ED in patients with NAFLD.
Socialized mitochondria: mitonuclear crosstalk in stress
Authors: Kim Kyung Hwa , Lee Cho Bi 
Published: May 2024

AbstractTraditionally, mitochondria are considered sites of energy production. However, recent studies have suggested that mitochondria are signaling organelles that are involved in intracellular interactions with other organelles. Remarkably, stressed mitochondria appear to induce a beneficial response that restores mitochondrial function and cellular homeostasis. These mitochondrial stress-centered signaling pathways have been rapidly elucidated in multiple organisms. In this review, we examine current perspectives on how mitochondria communicate with the rest of the cell, highlighting mitochondria-to-nucleus (mitonuclear) communication under various stresses. Our understanding of mitochondria as signaling organelles may provide new insights into disease susceptibility and lifespan extension.
Stress-induced epinephrine promotes hepatocellular carcinoma progression via the USP10-PLAGL2 signaling loop
Authors: Wang Chen , Ni Jiaping , Zhai Dongqing , Xu Yanchao , Wu Zijie , Chen Yuyuan , Liu Ning , Du Juan , Shen Yumeng , Liu Guilai , Yang Yong , You Linjun , Hu Weiwei 
Published: May 2024

AbstractHepatocellular carcinoma (HCC) is associated with a poor prognosis. Our previous study demonstrated that Pleomorphic adenoma gene like-2 (PLAGL2) was a potential therapeutic target in HCC. However, the mechanisms that lead to the upregulation of PLAGL2 in HCC remain unclear. The present study revealed that stress-induced epinephrine increased the expression of PLAGL2, thereby promoting the progression of HCC. Furthermore, PLAGL2 knockdown inhibited epinephrine-induced HCC development. Mechanistically, epinephrine upregulated ubiquitin-specific protease 10 (USP10) to stabilize PLAGL2 via the adrenergic β-receptor-2-c-Myc (ADRB2-c-Myc) axis. Furthermore, PLAGL2 acted as a transcriptional regulator of USP10, forming a signaling loop. Taken together, these results reveal that stress-induced epinephrine activates the PLAGL2-USP10 signaling loop to enhance HCC progression. Furthermore, PLAGL2 plays a crucial role in psychological stress-mediated promotion of HCC progression.
Mrgprb2-mediated mast cell activation exacerbates Modic changes by regulating immune niches
Authors: Ji Zhongyin , Li Jie , Tao Siyue , Li Hui , Kong Xiangxi , Huang Bao , Feng Zhenhua , Wei Xiaoan , Zheng Zeyu , Chen Jian , Chen Binhui , Liu Junhui , Zhao Fengdong 
Published: May 2024

AbstractModic changes are radiographic features associated with microfracture, low-virulence organism infection and chronic inflammation with inflammatory cell infiltration in the vertebral endplate region. Mast cells, as innate immune cells similar to macrophages, are present in painful degenerated intervertebral discs. However, the involvement and mechanisms of mast cells in the development of Modic changes remain unclear. Herein, we found increased mast cell infiltration in samples from patients with Modic changes and in mouse models of Modic changes. To clarify the role of mast cells in the progression of Modic changes, we used mast cell-deficient (KITW-SH/W-SH) mice to construct a model of Modic changes and found that the severity of Modic changes in KITW-SH/W-SH mice was significantly lower than that in WT mice. These findings were further supported by the use of a mast cell-specific activator (compound 48/80) and a stabilizer (cromolyn). Furthermore, we found that mast cells were not activated via the classic IgE pathway in the Modic change models and that Mrgprb2 is the specific receptor for mast cell activation reported in recent studies. Then, we utilized Mrgprb2 knockout mice to demonstrate that Mrgprb2 knockout inhibited mast cell activation and thus reduced the degree of Modic changes. Transcriptomic sequencing revealed aberrant PI3K-AKT and MAPK pathway activation in the Mrgprb2-deficient mast cells. Additionally, Mrgpbrb2-activated mast cells regulate immune niches by recruiting macrophages, promoting M1 polarization and reducing M2 polarization, thereby promoting the progression of Modic changes. These findings suggest that mast cells may serve as a novel therapeutic target for addressing Modic changes.
Factors that determine patients considering medication for the disease of obesity: an IMI2 SOPHIA study
Authors: Craig H. C. , Alsaeed D. , Heneghan H. , Al-Najim W. , Al Ozairi E. , le Roux C. W. 
Published: May 2024

Abstract
Objective
Obesity-related problems can now be managed with effective nutritional therapy, pharmacotherapy, and surgeries that achieve >10% weight loss. Assessing patient preferences, treatment choices, and factors affecting patients can improve treatment compliance and efficacy. Our aim was to identify factors affecting patient preference and subsequent choice of pharmacotherapy among those seeking treatment for obesity-related disorders.

Methods
A participatory action study using purposeful sampling recruited 33 patients with obesity complications. They were referred to specialist clinics in non-alcoholic fatty liver disease, diabetes mellitus, hypertension, and chronic kidney disease. Sixteen males and seventeen females aged 18–70 years, with BMI > 35 kg/m2 were recruited. Before the interview, participants watched a 60-minute video explaining nutritional therapy, pharmacotherapy, and surgery in equipoise. Data were collected in semi-structured interviews; Reflective thematic analysis was used. This sub study focuses only on patients who expressed specific attitudes (positive or negative) towards pharmacotherapy.

Results
Ten (30%) patients expressed a view on pharmacotherapy. Eight (24%) patients chose pharmacotherapy alone, whereas two (6%) patients chose pharmacotherapy combined with nutritional therapy. In this sub study focusing on pharmacotherapy, five themes were identified related to choosing whether or not to take medication: (1) attitudes towards pharmacotherapy, (2) attitudes toward size of obesity and its complications, (3) weighing the benefits and risks of treatment, (4) knowledge and reassurance of health professionals, and (5) costs associated with drug therapy.

Conclusion
The primary concerns regarding pharmacotherapy for intentional weight loss were efficacy, side effects, lifelong dosing, pharmacokinetics, and cost. Providing access to information about all the pharmacotherapies and the benefits is likely to result in greater penetrance of treatment.
The interplay between polygenic score for tumor necrosis factor-α, brain structural connectivity, and processing speed in major depression
Authors: Flinkenflügel Kira , Gruber Marius , Meinert Susanne , Thiel Katharina , Winter Alexandra , Goltermann Janik , Usemann Paula , Brosch Katharina , Stein Frederike , Thomas-Odenthal Florian , Wroblewski Adrian , Pfarr Julia-Katharina , David Friederike S. , Beins Eva C. , Grotegerd Dominik , Hahn Tim , Leehr Elisabeth J. , Dohm Katharina , Bauer Jochen , Forstner Andreas J. , Nöthen Markus M. , Jamalabadi Hamidreza , Straube Benjamin , Alexander Nina , Jansen Andreas , Witt Stephanie H. , Rietschel Marcella , Nenadić Igor , van den Heuvel Martijn P. , Kircher Tilo , Repple Jonathan , Dannlowski Udo 
Published: May 2024

AbstractReduced processing speed is a core deficit in major depressive disorder (MDD) and has been linked to altered structural brain network connectivity. Ample evidence highlights the involvement of genetic-immunological processes in MDD and specific depressive symptoms. Here, we extended these findings by examining associations between polygenic scores for tumor necrosis factor-α blood levels (TNF-α PGS), structural brain connectivity, and processing speed in a large sample of MDD patients. Processing speed performance of n = 284 acutely depressed, n = 177 partially and n = 198 fully remitted patients, and n = 743 healthy controls (HC) was estimated based on five neuropsychological tests. Network-based statistic was used to identify a brain network associated with processing speed. We employed general linear models to examine the association between TNF-α PGS and processing speed. We investigated whether network connectivity mediates the association between TNF-α PGS and processing speed. We identified a structural network positively associated with processing speed in the whole sample. We observed a significant negative association between TNF-α PGS and processing speed in acutely depressed patients, whereas no association was found in remitted patients and HC. The mediation analysis revealed that brain connectivity partially mediated the association between TNF-α PGS and processing speed in acute MDD. The present study provides evidence that TNF-α PGS is associated with decreased processing speed exclusively in patients with acute depression. This association was partially mediated by structural brain connectivity. Using multimodal data, the current findings advance our understanding of cognitive dysfunction in MDD and highlight the involvement of genetic-immunological processes in its pathomechanisms.
New perspective on sustained antidepressant effect: focus on neurexins regulating synaptic plasticity
Authors: Ruan Yuan , Yuan Ruolan , He Jiaqi , Jiang Yutong , Chu Shifeng , Chen Naihong 
Published: May 2024

AbstractDepression is highly prevalent globally, however, currently available medications face challenges such as low response rates and short duration of efficacy. Additionally, depression mostly accompany other psychiatric disorders, further progressing to major depressive disorder without long-term effective management. Thus, sustained antidepressant strategies are urgently needed. Recently, ketamine and psilocybin gained attention as potential sustained antidepressants. Review of recent studies highlights that synaptic plasticity changes as key events of downstream long-lasting changes in sustained antidepressant effect. This underscores the significance of synaptic plasticity in sustained antidepressant effect. Moreover, neurexins, key molecules involved in the regulation of synaptic plasticity, act as critical links between synaptic plasticity and sustained antidepressant effects, involving mechanisms including protein level, selective splicing, epigenetics, astrocytes, positional redistribution and protein structure. Based on the regulation of synaptic plasticity by neurexins, several drugs with potential for sustained antidepressant effect are also discussed. Focusing on neurexins in regulating synaptic plasticity promises much for further understanding underlying mechanisms of sustained antidepressant and the next step in new drug development. This research represents a highly promising future research direction.
Mixed-methods evaluation of an enhanced asthma biologics clinical pathway in the West Midlands UK
Authors: Damery Sarah , Jones Janet , Idris Elfatih , Cooper Angela , Minshall Holly , Clowes Chris , Jolly Kate 
Published: May 2024

AbstractBiologic treatments can alleviate severe asthma symptoms and reduce health service use. However, service capacity limits and low referral rates from primary care indicate unmet patient need. We report a mixed-methods evaluation of an enhanced severe asthma pathway implemented in Staffordshire and Stoke-on-Trent, UK which aimed to optimise primary care referrals through training/education, and increased capacity in specialist clinics. Quantitative analysis assessed patient wait times between pathway stages, prescribing changes, exacerbations, hospital admissions and asthma control. Interviews with 12 stakeholders evaluated perceptions of the enhanced pathway across settings. In 12 months, 564 patients from 28 general practices were reviewed for biologics eligibility, of whom 125 (22.2%) were referred for specialist assessment. Wait times were significantly lower under the enhanced pathway when compared against historic patients following the standard pathway, and reduced overall from a mean of 76.4 to 26.7 weeks between referral and biologics initiation (p < 0.001). Patients commencing biologics (n = 46) showed significantly reduced reliever inhaler prescribing rates (p = 0.037), 60% lower oral steroid use (p < 0.001), significantly reduced exacerbation rates (p < 0.001) and fewer hospital admissions (p < 0.001) compared with the 12 months pre-treatment. Mean asthma control scores reduced from 3.13 pre-initiation to 1.89 post-initiation (p < 0.001) – a clinically significant improvement. Interviewees viewed the enhanced pathway positively, although ongoing issues related to difficulties engaging primary care amid concerns around increased workloads and pathway capacity. The large number of referrals generated from a comparatively small number of general practices confirms substantial unmet need that an enhanced severe asthma pathway could help address if implemented routinely.
Frequent disturbances enhanced the resilience of past human populations
Authors: Riris Philip , Silva Fabio , Crema Enrico , Palmisano Alessio , Robinson Erick , Siegel Peter E. , French Jennifer C. , Jørgensen Erlend Kirkeng , Maezumi Shira Yoshi , Solheim Steinar , Bates Jennifer , Davies Benjamin , Oh Yongje , Ren Xiaolin 
Published: May 2024

AbstractThe record of past human adaptations provides crucial lessons for guiding responses to crises in the future1–3. To date, there have been no systematic global comparisons of humans’ ability to absorb and recover from disturbances through time4,5. Here we synthesized resilience across a broad sample of prehistoric population time–frequency data, spanning 30,000 years of human history. Cross-sectional and longitudinal analyses of population decline show that frequent disturbances enhance a population’s capacity to resist and recover from later downturns. Land-use patterns are important mediators of the strength of this positive association: farming and herding societies are more vulnerable but also more resilient overall. The results show that important trade-offs exist when adopting new or alternative land-use strategies.
Multimodal decoding of human liver regeneration
Authors: Matchett K. P. , Wilson-Kanamori J. R. , Portman J. R. , Kapourani C. A. , Fercoq F. , May S. , Zajdel E. , Beltran M. , Sutherland E. F. , Mackey J. B. G. , Brice M. , Wilson G. C. , Wallace S. J. , Kitto L. , Younger N. T. , Dobie R. , Mole D. J. , Oniscu G. C. , Wigmore S. J. , Ramachandran P. , Vallejos C. A. , Carragher N. O. , Saeidinejad M. M. , Quaglia A. , Jalan R. , Simpson K. J. , Kendall T. J. , Rule J. A. , Lee W. M. , Hoare M. , Weston C. J. , Marioni J. C. , Teichmann S. A. , Bird T. G. , Carlin L. M. , Henderson N. C. 
Published: May 2024

AbstractThe liver has a unique ability to regenerate1,2; however, in the setting of acute liver failure (ALF), this regenerative capacity is often overwhelmed, leaving emergency liver transplantation as the only curative option3–5. Here, to advance understanding of human liver regeneration, we use paired single-nucleus RNA sequencing combined with spatial profiling of healthy and ALF explant human livers to generate a single-cell, pan-lineage atlas of human liver regeneration. We uncover a novel ANXA2+ migratory hepatocyte subpopulation, which emerges during human liver regeneration, and a corollary subpopulation in a mouse model of acetaminophen (APAP)-induced liver regeneration. Interrogation of necrotic wound closure and hepatocyte proliferation across multiple timepoints following APAP-induced liver injury in mice demonstrates that wound closure precedes hepatocyte proliferation. Four-dimensional intravital imaging of APAP-induced mouse liver injury identifies motile hepatocytes at the edge of the necrotic area, enabling collective migration of the hepatocyte sheet to effect wound closure. Depletion of hepatocyte ANXA2 reduces hepatocyte growth factor-induced human and mouse hepatocyte migration in vitro, and abrogates necrotic wound closure following APAP-induced mouse liver injury. Together, our work dissects unanticipated aspects of liver regeneration, demonstrating an uncoupling of wound closure and hepatocyte proliferation and uncovering a novel migratory hepatocyte subpopulation that mediates wound closure following liver injury. Therapies designed to promote rapid reconstitution of normal hepatic microarchitecture and reparation of the gut–liver barrier may advance new areas of therapeutic discovery in regenerative medicine.
A body–brain circuit that regulates body inflammatory responses
Authors: Jin Hao , Li Mengtong , Jeong Eric , Castro-Martinez Felipe , Zuker Charles S. 
Published: May 2024

AbstractThe body–brain axis is emerging as a principal conductor of organismal physiology. It senses and controls organ function1,2, metabolism3 and nutritional state4–6. Here we show that a peripheral immune insult strongly activates the body–brain axis to regulate immune responses. We demonstrate that pro-inflammatory and anti-inflammatory cytokines communicate with distinct populations of vagal neurons to inform the brain of an emerging inflammatory response. In turn, the brain tightly modulates the course of the peripheral immune response. Genetic silencing of this body–brain circuit produced unregulated and out-of-control inflammatory responses. By contrast, activating, rather than silencing, this circuit affords neural control of immune responses. We used single-cell RNA sequencing, combined with functional imaging, to identify the circuit components of this neuroimmune axis, and showed that its selective manipulation can effectively suppress the pro-inflammatory response while enhancing an anti-inflammatory state. The brain-evoked transformation of the course of an immune response offers new possibilities in the modulation of a wide range of immune disorders, from autoimmune diseases to cytokine storm and shock.