bluuebunny/crossref_metadata_2025_split huggingface dataset:
Trends in Coupled Human-Environment Systems Modelling: A Scoping Review
Authors: Thampi Vivek A. , Bauch Chris T. , Anand Madhur 
Published: November 2024

AbstractClassical environmental models assume the influence of humans on environmental systems is constant. However, human and environmental systems respond to one another. As such, coupled human-environment systems (CHES) models have been developed and are becoming more widely studied. In this review, we analyze CHES modelling techniques and study systems over a decade (May 2009-April 2019). We utilized the PRISMA method to filter publications from both Web of Knowledge and PUBMED, yielding 92 relevant papers for our review. Publications more than doubled from the 5-year interval May 2009-December 2013 (28/92) to the 5-year interval January 2014-April 2019 (64/92). CHES models typically used either differential equations (DEs) (44/92) or agent-based models (ABMs) (28/92). We organized the included literature with respect to the technique used to represent human behaviour. We noticed a diversity of approaches in this respect, but primarily optimization techniques (28/92) and game theory (34/92). We noticed a substantial increase in publications using more highly structured models in the second 5-year interval. We attribute this to reduced technological barriers to developing more detailed models, and greater data availability. We discuss the realism of the models and their ability to capture real-world dynamics. Finally, we explore avenues for future research, and discuss unconventional routes such as online communities and artificial intelligence modelling to expand representation of human behaviour in CHES models.
Increase ofClostridioides difficilePCR ribotype 002 infection coincides with decreased disease severity in hospitalized patients in the Netherlands
Authors: Baktash A , Harmanus C , Goeman J , Brennan W , Cormican M , Corver J , Kuijper EJ , Smits WK 
Published: November 2024

ABSTRACTClostridioides difficilePCR ribotype (RT) 002 is the second most prevalent RT in the Netherlands. In 2019, an increase inC. difficileinfections (CDI) due to a clonal RT002 strains was reported in Ireland. In retrospect, a significant increase in the proportion of CDI due to RT002 was detected in the Netherlands between May 2017-May 2018 (11.9% of 683 cases vs 6.5% of 865 in the previous year). Our aim was to analyze and characterize CDI due to RT002 over time and to assess whether RT002 isolates in the Netherlands were related to the Irish RT002 isolates.Over the period May 2009-April 2021, Dutch patients with CDI due to RT002 showed less severe CDI (22%) in comparison with hypervirulent RTs (RT027; 29% and RT078; 25%), similar to grouped data from other non-hypervirulent ribotypes (21%). However, RT002-associated CDI prior to the increased proportion (2009-2017) showed CDI severity similar to CDI associated with hypervirulent types, whereas this was no longer the case after the increase (2017-2021). Using core genome MLST, Dutch isolates were found not to be related to the Irish outbreak strain. Several Dutch strains clustered together without an evident epidemiological link, suggesting recent emergence.ImportanceClostridioides difficileis a significant cause of hospital-associated infections, making it relevant to understand the emergence and spread of different ribotypes. This study highlights a rise in cases of PCR ribotype 002 (RT002) in the Netherlands, suggesting changes in its prevalence. Despite the increase in RT002 infections, the severity of disease appears to have decreased and is lower compared to more virulent ribotypes. Further research is needed to understand the factors driving this change. Additionally, this study underscores some limitations of core genome multi-locus sequence typing (cgMLST). cgMLST is valuable for identifying genetic relationships, however it cannot always distinguish between widespread recently emerged strains and local transmission chains, making it challenging to determine the exact sources of infection. Continued surveillance and genetic characterization ofC. difficileare essential to better understand these trends and improve control measures.
Genome-wide association studies and multi-omics integrative analysis reveal novel loci and their molecular mechanisms for circulating polyunsaturated, monounsaturated, and saturated fatty acids
Authors: Sun Yitang , Xu Huifang , Ye Kaixiong 
Published: November 2024

AbstractPrevious genome-wide association studies (GWAS) have identified genetic loci associated with the circulating levels of FAs, but the biological mechanisms of these genetic associations remain largely unexplored. Here, we conducted GWAS to identify additional genetic loci for 19 circulating fatty acid (FA) traits in UK Biobank participants of European ancestry (N = 239,268) and five other ancestries (N = 508 – 4,663). We leveraged the GWAS findings to characterize genetic correlations and colocalized regions among FAs, explore sex differences, examine FA loci influenced by lipoprotein metabolism, and apply statistical fine-mapping to pinpoint putative causal variants. We integrated GWAS signals with multi-omics quantitative trait loci (QTL) to reveal intermediate molecular phenotypes mediating the associations between the genetic loci and FA levels. Altogether, we identified 215 significant loci for polyunsaturated fatty acids (PUFAs)-related traits in European participants, 163 loci for monounsaturated fatty acids (MUFAs)-related traits, and 119 loci for saturated fatty acids (SFAs)-related traits, including 70, 61, and 54 novel loci, respectively. A novel locus for total FAs, the percentage of omega-6 PUFAs in total FAs, and total MUFAs (around genesGSTT1/2/2B) overlapped with QTL signals for all six molecular phenotypes examined, including gene expression, protein abundance, DNA methylation, splicing, histone modification, and chromatin accessibility. Across 19 FA traits, 65% of GWAS loci overlapped with QTL signals for at least one molecular phenotype. Our study identifies novel genetic loci for circulating FA levels and systematically uncovers their underlying molecular mechanisms.
Modified-Mindfulness-Based Stress Reduction as a Treatment for Cognitive Recovery in Patients with Minor Stroke: a Randomized Controlled Pilot Study
Authors: Girgenti Sophia G. , Dallasta Isabella , Lawrence Erin , Merbach Dawn , Simon Jonathan Z. , Llinas Rafael , Gould Neda F. , Marsh Elisabeth Breese 
Published: November 2024

AbstractBackgroundWell-developed rehabilitation paradigms exist for post-stroke language and motor impairments. However, no such recovery program has been identified for commonly disabling cognitive deficits in patients following minor stroke. Mindfulness Based Stress Reduction (MBSR) is thought to engage the frontal lobes, improving concentration and attention, and therefore may be an effective option.MethodsWe prospectively enrolled a cohort of patients with subacute minor stroke and randomized them to either an 8-week online modified-MBSR course or online traditional Stroke Support Group (SSG). All patients underwent a battery of cognitive tests and measures of patient reported outcomes (PROs) pre- and post-intervention. ANOVA was used to compare changes in scores over time across both groups, as well as a third group of control patients having received neither intervention (n=128).ResultsA total of 30 patients were randomized (n=16 for m-MBSR; n=14 for SSG). The average age of the cohort was 65.9 years. Both groups scored similarly on assessments one-month post-stroke and demonstrated increased T-scores on cognitive tasks at the 3-month visit. However, the m-MBSR group showed moderately elevated levels of improvement, specifically in processing speed, executive, and global cognitive function. Level of engagement was not associated with better clinical scores, though was unexpectedly low for both groups.Conclusionsm-MBSR appears to modestly improve frontal lobe activity and demonstrates some success in increasing cognitive performance. However, further studies are needed to determine if it is more efficacious in the chronic stage of recovery when more patients are able to fully engage and actively participate.
Large Language Models Fail to Reproduce Level I Recommendations for Breast Radiotherapy
Authors: Tang Kathleen , Han John , Wu Shengyang 
Published: November 2024

AbstractThis study evaluates the reliability of the largest public-facing large language models in providing accurate breast cancer radiotherapy recommendations. We assessed ChatGPT 3.5, ChatGPT 4, ChatGPT 4o, Claude 3.5 Sonnet, and ChatGPT o1 in three common clinical scenarios. The clinical cases are as follows: post-lumpectomy radiotherapy in a 40 year old woman, (2) postmastectomy radiation in a 40 year old woman with 4+ lymph nodes, and (3) postmastectomy radiation in an 80 year old woman with early stage tumor and negative axillary dissection. Each case was designed to be unambiguous with respect to the Level I evidence and clinical guideline-supported approach. The evidence-supported radiation treatments are as follows: (1) Whole breast with boost (2) Regional nodal irradiation (3) Omission of post-operative radiotherapy. Each prompt is presented to each LLM multiple times to ensure reproducibility. Results indicate that the free, public-facing models often fail to provide accurate treatment recommendations, particularly when omission of radiotherapy was the correct course of action. Many recommendations suggested by the LLMs increase morbidity and mortality in patients. Models only accessible through paid subscription (ChatGPT o1 and o1-mini) demonstrated greatly improved accuracy. Some prompt-engineering techniques, rewording and chain-of-reasoning, enhanced the accuracy of the LLMs, while true/false questioning significantly worsened results. While public-facing LLMs show potential for medical applications, their current reliability is unsuitable for clinical decision-making.
Association of Physical Activity from Wearable Devices and Chronic Disease Risk: Insights from the All of Us Research Program
Authors: Hou Yu , Cui Erjia , Ikramuddin Sayeed , Zhang Rui 
Published: November 2024

AbstractBackgroundPhysical activity is widely recognized as a key modifiable factor for reducing the risk of chronic diseases. Wearable devices such as Fitbit offer a unique opportunity to objectively measure physical activity metrics, providing insights into the association between different types of physical activity and chronic disease risk.ObjectiveThis study aims to examine the association between physical activity metrics derived from Fitbit devices and the incidence of various chronic diseases among participants from the All of Us Research Program.MethodsPhysical activity metrics included daily steps, elevation gain, and activity durations at different intensities (e.g., very active, lightly active, and sedentary). Cox proportional hazards models and multiple regression models were used to assess the relationship between these metrics and the incidence of chronic diseases represented by Phecodes. Age, sex, and body mass index (BMI) were included as covariates.ResultsA total of 15,538 participants provided Fitbit activity data, of which 9,320 also had electronic health records (EHR). Increased daily step count, elevation gain, and very active minutes were significantly associated with a reduced risk of several chronic conditions, including obesity, Type 2 diabetes, and major depressive disorder. Conversely, increased sedentary time was linked to higher risks for conditions such as obesity, Type 2 diabetes, and essential hypertension. Multiple regression analyses confirmed these associations.ConclusionOur findings highlight the beneficial effects of increased physical activity, particularly daily steps and elevation gain, on reducing the risk of chronic diseases. Conversely, sedentary behavior remains a significant risk factor for the development of several conditions. These insights may inform personalized activity recommendations aimed at reducing disease burden and improving population health outcomes.
Granger causality connectivity analysis of persistent atrial fibrillation dynamics reveals mechanistic insights into the posterior wall
Authors: Barker Joseph , Sau Arunashis , Bajaj Nikesh , Jenkins Alex , Sharp Alex , Shi Xili , Li Xinyang , Karim Nabeela , Handa Balvinder , Chambers Richard , Betts Timothy , Peters Nicholas S , Wong Tom , Ng Fu Siong 
Published: November 2024

AbstractBackgroundPulmonary vein isolation (PVI) is the mainstay of ablation for atrial fibrillation (AF). Adjunctive posterior wall isolation (PWI) has not demonstrated convincing additional benefit. To provide mechanistic underpinnings as to why empirical PWI does not improve outcomes, we undertook Granger Causality (GC) analysis of patient-specific AF dynamics before and after ablation.MethodsA prospective cohort study was undertaken at Royal Brompton Hospital. Consecutive patients undergoing PVI with left atrial electro-anatomical noncontact mapping (AcQmap; Acutus Medical) were included. GC analysis was undertaken before and after PVI but before adjunctive ablation.ResultsIn 21 consecutive patients, Causality Pairing Index, a Granger Causality-based measure of AF organisation, was unchanged post PVI; overall 0.087±0.012 vs. 0.086±0.015, p = 0.64, or by region (posterior wall; 0.084±0.020 vs 0.079±0.017, p = 0.20, rest of LA 0.087±0.013 vs 0.086±0.016, p = 0.80). Directional dispersion, quantifying conduction heterogeneity, was lower in the PW compared to the rest of the LA (0.093±0.036 vs 0.11±0.043, p = 0.017) and increased following PVI (0.093±0.036 vs 0.12±0.043, p = 0.045), while there was no change in the rest of the LA (0.11±0.034 vs 0.11±0.030, p =0.52). Net outflow for left atrial posterior wall decreased following PVI (pre −0.0086±0.047 vs −0.033±0.054, p=0.011), suggesting that in the majority of cases the posterior wall becomes a net sink after PVIConclusionWe describe the first application of GC to global, simultaneous AF mapping data. GC analysis suggests, on average, the posterior wall is a net sink following PVI, and therefore PWI will not be beneficial in the majority of patients, providing mechanistic insight into null randomised control trials for PWI. GC is positioned as a valuable clinical decision tool to select the minority of patients that may benefit from PWI to guide personalised PsAF ablation strategies.Clinical PerspectiveWhat is Known:Pulmonary vein isolation (PVI) is a standard treatment for atrial fibrillation (AF) ablation, but adjunctive posterior wall isolation (PWI) has not demonstrated consistent additional clinical benefit.What the Study Adds:Granger Causality analysis of AF dynamics indicates that, following PVI, the left atrial posterior wall becomes a net sink in most cases.This finding provides mechanistic insight into why PWI does not improve outcomes for most patients, explaining the null results in randomised trials.The study supports using Granger Causality as a decision tool to personalise ablation strategies, identifying the minority of patients who may benefit from PWI.Graphical Abstract
Sex-Related Differences in Endovascular Treatment Outcomes for Acute Large Infarcts: The ANGEL-ASPECT Subgroup Analysis
Authors: Sun Dapeng , Guo Xin , Jiao Liwen , Nguyen Thanh N , Abdalkader Mohamad , Pan Yuesong , Wang Mengxing , Luo Gang , Jia Baixue , Tong Xu , Ma Ning , Gao Feng , Mo Dapeng , Raynald  , Huo Xiaochuan , Miao Zhongrong ,   ANGEL-ASPECT study group
Published: November 2024

AbstractBackground and PurposeThe outcomes of endovascular therapy (EVT) across sexes for large infarcts remains unclear. This study aimed to evaluate the impact of sex on the outcomes of EVT for patients with large infarct.MethodsIn this secondary analysis of the ANGEL-ASPECT trial, we compared baseline characteristics and clinical outcomes between men and women, and each cohort further divided into EVT and medical management (MM) groups. The primary outcome was the 90-day modified Rankin Scale (mRS) score distribution. Safety outcomes included symptomatic intracranial hemorrhage (sICH) within 48 h and mortality within 90 days.ResultsThere were 177 of 455 patients enrolled in the ANGEL-ASPECT trial who were women. 53.7% (95/177) of women and 48.6% (135/278) of men underwent EVT, respectively. The treatment effect of EVT didn’t vary in both sexes with large infarcts (all P >0.05 for interaction). Compared to MM, EVT improved 90-day functional outcomes for both men (3[2-5] vs. 4[3-5], common odds ratio [cOR]: 1.92, 95% CI: 1.26–2.95, P=0.003) and women (4[3-6] vs. 5[4-6], cOR: 2.50, 95% CI: 1.41–4.44, P=0.002). The sICH rate wasn’t different in both treatment groups across both sexes (Men: 5.2% vs. 2.8%, RR: 2.04, 95%CI: 0.56-7.47, P=0.28; Women:7.4% vs. 2.4%, RR:3.00, 95%CI:0.57-15.68, P=0.19).ConclusionIn patients with large ischemic infarct, the treatment effect of EVT didn’t differ between women and men, with better outcomes with EVT versus MM, without an increased risk of sICH. These findings emphasize the need for equal attention and care for both sexes with large infarcts in clinical practice.
GHT-SELEX demonstrates unexpectedly high intrinsic sequence specificity and complex DNA binding of many human transcription factors
Authors: Jolma Arttu , Hernandez-Corchado Aldo , Yang Ally W.H. , Fathi Ali , Laverty Kaitlin U. , Brechalov Alexander , Razavi Rozita , Albu Mihai , Zheng Hong ,   The Codebook Consortium, Kulakovskiy Ivan V. , Najafabadi Hamed S. , Hughes Timothy R. 
Published: November 2024

SUMMARYA long-standing challenge in human regulatory genomics is that transcription factor (TF) DNA-binding motifs are short and degenerate, while the genome is large. Motif scans therefore produce many false-positive binding site predictions. By surveying 179 TFs across 25 families using >1,500 cyclicin vitroselection experiments with fragmented, naked, and unmodified genomic DNA – a method we term GHT-SELEX (Genomic HT-SELEX) – we find that many human TFs possess much higher sequence specificity than anticipated. Moreover, genomic binding regions from GHT-SELEX are often surprisingly similar to those obtainedin vivo(i.e. ChIP-seq peaks). We find that comparable specificity can also be obtained from motif scans, but performance is highly dependent on derivation and use of the motifs, including accounting for multiple local matches in the scans. We also observe alternative engagement of multiple DNA-binding domains within the same protein: long C2H2 zinc finger proteins often utilize modular DNA recognition, engaging different subsets of their DNA binding domain (DBD) arrays to recognize multiple types of distinct target sites, frequently evolving via internal duplication and divergence of one or more DBDs. Thus, contrary to conventional wisdom, it is common for TFs to possess sufficient intrinsic specificity to independently delineate cellular targets.
An integrative approach to prioritize candidate causal genes for complex traits in cattle
Authors: Ghoreishifar Mohammad , Macleod Iona M. , Chamberlain Amanda J. , Liu Zhiqian , Lopdell Thomas J. , Littlejohn Mathew D. , Xiang Ruidong , Pryce Jennie E. , Goddard Michael E. 
Published: November 2024

AbstractGenome-wide association studies (GWAS) have identified many quantitative trait loci (QTL) associated with complex traits, predominantly in non-coding regions, posing challenges in pinpointing the causal variants and their target genes. Three types of evidence can help identify the gene through which QTL act: (1) proximity to the most significant GWAS variant, (2) correlation of gene expression with the trait, and (3) the gene’s physiological role in the trait. However, there is still uncertainty in the success of these methods in identifying the correct genes. Here we test the ability of these methods in a comparatively simple series of traits associated with the concentration of polar lipids in milk.We conducted single-trait GWAS for ∼14 million imputed variants and 56 individual milk polar lipid (PL) phenotypes in 336 cows. A meta-analysis of multi-trait GWAS identified 10,063 significant SNPs at FDR ≤ 10% (P≤ 7.15E-5). Transcriptome data from blood (∼12.5K genes, 143 cows) and mammary tissue (∼12.2K genes, 169 cows) were analysed using the genetic score omics regression (GSOR) method. This method links observed gene expression to genetically predicted phenotypes and was used to find associations between gene expression and 56 PL phenotypes. GSOR identified 2,186 genes in blood and 1,404 in mammary tissue associated with at least one PL phenotype (FDR ≤ 1%). We partitioned the genome into non-overlapping windows of 100 Kb to test for overlap between GSOR-identified genes and GWAS signals. We found a significant overlap between these two datasets, indicating GSOR significant genes were more likely to be located within 100 Kb windows that have GWAS signals compared to those without (P= 0.01; odds ratio = 1.47). These windows included 70 significant genes expressed in mammary tissue and 95 in blood. Compared to all expressed genes in each tissue, these genes were enriched for lipid metabolism gene ontology (GO). That is, 7 of the 70 significant mammary transcriptome genes (P< 0.01; odds ratio = 3.98) and 5 of the 95 significant blood genes (P< 0.10; odds ratio = 2.24) were involved in lipid metabolism GO. The candidate causal genes includeDGAT1,ACSM5,SERINC5,ABHD3,CYP2U1,PIGL,ARV1,SMPD5, andNPC2, with some overlap between the two tissues.The overlap between GWAS, GSOR, and GO analyses suggests that together these methods can identify genes mediating QTL, though their power remains limited, as reflected by modest odds ratios. Larger sample sizes would enhance the power of these analyses, but issues like linkage disequilibrium would remain.
System-level characterization of engineered and evolved formatotrophicE. colistrains
Authors: Yilmaz Suzan , Kanis Boas , Hogers Rensco A. H. , Benito-Vaquerizo Sara , Kahnt Jörg , Glatter Timo , Dronsella Beau , Erb Tobias J. , Suarez-Diez Maria , Claassens Nico J. 
Published: November 2024

AbstractOne-carbon compounds, such as formate, are promising and sustainable feedstocks for microbial bioproduction of fuels and chemicals. Growth ofEscherichia colion formate was recently achieved by introducing the reductive glycine pathway (rGlyP) into its genome, which is theoretically the most energy-efficient aerobic formate assimilation pathway. While adaptive laboratory evolution was used to enhance the growth rate and biomass yield significantly, still the best performing formatotrophicE. colistrain did not approach the theoretical optimal biomass yield of the rGlyP. In this study, we investigated these previously engineered formatotrophicE. colistrains to find out why the biomass yield was sub-optimal and how it may be improved. Through a combination of metabolic modelling, genomic and proteomic analysis, we identified several potential metabolic bottlenecks and future targets for optimization. This study also reveals further insights in the evolutionary mutations and related changes in proteome allocation that supported the already substantially improved growth of formatotrophicE. colistrain. This systems-level analysis provides key insights to realize high-yield, fast growing formatotrophic strains for future bioproduction.