bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protection from T cell-dependent colitis by the helminth-derived immunomodulatory mimic of transforming growth factor-β,Hp-TGM
Authors: Smyth Danielle J , White Madeleine P J , Johnston Chris J C , Donachie Anne-Marie , Campillo Poveda Marta , McSorley Henry J , Maizels Rick M 
Published: January 2023

AbstractIn animal models of inflammatory colitis, pathology can be ameliorated by several intestinal helminth parasites, including the mouse nematode Heligmosomoides polygyrus. To identify parasite products that may exert anti-inflammatory effects in vivo, we tested H. polygyrus excretory–secretory (HES) products, as well as a recombinantly expressed parasite protein, transforming growth factor mimic (TGM), that functionally mimics the mammalian immunomodulatory cytokine TGF-β. HES and TGM showed a degree of protection in dextran sodium sulphate-induced colitis, with a reduction in inflammatory cytokines, but did not fully block the development of pathology. HES also showed little benefit in a similar acute trinitrobenzene sulphonic acid-induced model. However, in a T cell transfer-mediated model with recombination activation gene (RAG)-deficient mice, HES-reduced disease scores if administered throughout the first 2 or 4 weeks following transfer but was less effective if treatment was delayed until 14 days after T cell transfer. Recombinant TGM similarly dampened colitis in RAG-deficient recipients of effector T cells, and was effective even if introduced only once symptoms had begun to be manifest. These results are a promising indication that TGM may replicate, and even surpass, the modulatory properties of native parasite HES.
Trajectory and correlates of pulmonary congestion by lung ultrasound in patients with acute myocardial infarction: insights from PARADISE-MI
Authors: Platz Elke , Claggett Brian , Jering Karola S , Kovacs Attila , Cikes Maja , Winzer Ephraim B , Rad Aria , Lefkowitz Martin P , Gong Jianjian , Køber Lars , McMurray John J V , Solomon Scott D , Pfeffer Marc A , Shah Amil 
Published: January 2023

AbstractAimPARADISE-MI examined the efficacy of sacubitril/valsartan in acute myocardial infarction (AMI) complicated by reduced left ventricular ejection fraction (LVEF), pulmonary congestion, or both. We sought to assess the trajectory of pulmonary congestion using lung ultrasound (LUS) and its association with cardiac structure and function in a pre-specified substudy.Methods and resultsPatients without prior heart failure (HF) underwent eight-zone LUS and echocardiography at baseline (±2 days of randomization) and after 8 months. B-lines were quantified offline, blinded to treatment, clinical findings, time point, and outcomes. Among 152 patients (median age 65, 32% women, mean LVEF 41%), B-lines were detectable in 87% at baseline [median B-line count: 4 (interquartile range 2–8)]. Among 115 patients with LUS data at baseline and follow-up, B-lines decreased significantly from baseline (mean ± standard deviation: −1.6 ± 7.3; P = 0.018). The proportion of patients without pulmonary congestion at follow-up was significantly higher in those with fewer B-lines at baseline. Adjusted for baseline, B-lines at follow-up were on average 6 (95% confidence interval: 3–9) higher in patients who experienced an intercurrent HF event vs. those who did not (P = 0.001). A greater number of B-lines at baseline was associated with larger left atrial size, higher E/e′ and E/A ratios, greater degree of mitral regurgitation, worse right ventricular systolic function, and higher tricuspid regurgitation velocity (P-trend &lt;0.05 for all).ConclusionIn this AMI cohort, B-lines, indicating pulmonary congestion, were common at baseline and, on average, decreased significantly from baseline to follow-up. Worse pulmonary congestion was associated with prognostically important echocardiographic markers.
Caplacizumab for treating subacute intra-stent thrombus occurring despite efficacious double anti-platelet treatment and anticoagulation: a case report
Authors: Stalder Gregoire , Chatte Antoine , De Rossi Noemy , Yerly Patrick , Alberio Lorenzo , Eeckhout Eric 
Published: January 2023

AbstractBackgroundAcute and subacute stent thromboses are a rare complication associated with high mortality and morbidity occurring in ∼1.5% of patients treated with primary percutaneous intervention for ST-elevation myocardial infarction (STEMI). Recent publications describe a potential role of the von Willebrand factor (VWF) in thrombus formation at sites of critical coronary stenosis in STEMI.Case summaryWe describe a 58-year-old woman with STEMI at initial presentation, who suffered subacute stent thrombosis despite good stent expansion, efficacious dual antiplatelet therapy, and therapeutic anticoagulation. Because of very high VWF values, we administered N-acetylcysteine in order to depolymerize VWF, but the drug was not well tolerated. Since the patient was still symptomatic, we used caplacizumab in order to prevent VWF from interacting with platelets. Under this treatment, the clinical and angiographic course was favourable.DiscussionConsidering a modern view of intracoronary thrombus pathophysiology, we describe an innovative treatment approach, which eventually ended in a favourable outcome.
Transient decrease in the depth of the negative T wave in apical hypertrophic cardiomyopathy is a sign of left anterior descending artery stenosis: a case series
Authors: Arima Naoki , Ochi Yuri , Takahashi Makoto , Moriki Toshihiro , Noguchi Tatsuya , Kubo Toru , Yamasaki Naohito , Kitaoka Hiroaki 
Published: January 2023

Abstract

Background
In patients with apical hypertrophic cardiomyopathy (HCM), electrocardiography (ECG) often shows left ventricular hypertrophy (LVH) and a negative T wave. A negative T wave often disappears over time due to degeneration of the apical myocardium. However, there are limited reports on the temporary change of a negative T wave in patients with HCM.

Case summary
We report three apical HCM patients with LVH and T wave inversion on their previous ECG who showed a temporary decrease in the depth of the negative T wave. All of them had significant stenosis of coronary arteries including the left anterior descending artery (LAD). After revascularization for the LAD lesion, their ECG returned to the previous depth of the negative T wave.

Discussion
The cases presented here suggested that a temporary decrease in the depth of the negative T wave in apical HCM patients may be one of the signs of ischaemia in the anterior-apical region caused by severe stenosis of the LAD.
Cognitive-behavioural therapy reduces psychological distress in younger patients with cardiac disease: a randomized trial
Authors: Holdgaard Annette , Eckhardt-Hansen Christine , Lassen Christina Funch , Kjesbu Ingunn Eklo , Dall Christian Have , Michaelsen Kristine Lund , Sibilitz Kirstine Lærum , Prescott Eva , Rasmusen Hanne Kruuse 
Published: January 2023

AbstractAimsTo test whether usual outpatient cardiac rehabilitation (CR) supplemented by a cognitive-behavioural therapy (CBT) intervention may reduce anxiety and depression compared with usual CR.Methods and resultsIn this multicentre randomized controlled trial, 147 cardiac patients (67% men, mean age 54 years, 92% with coronary artery disease) with psychological distress defined as a hospital anxiety and depression scale (HADS) anxiety or depression score ≥8 were randomized to five sessions of group CBT plus usual CR (intervention, n = 74) or CR alone (control, n = 73). Patients with severe distress or a psychiatric diagnosis were excluded. The intervention was delivered by cardiac nurses with CBT training and supervised by a psychologist. A reference, non-randomized group (background, n = 41) of consecutive patients without psychological distress receiving usual CR was included to explore the effect of time on HADS score. The primary outcome, total HADS score after 3 months, improved more in the intervention than in the control group [the mean total HADS score improved by 8.0 (standard deviation 5.6) vs. 4.1 (standard deviation 7.8), P &lt; 0.001]. Significant between-group differences were maintained after 6 months. Compared with the control group, the intervention group also had greater adherence to CR (P = 0.003), more improvement in the heart-related quality of life (HeartQoL) at 6 months (P &lt; 0.01), and a significant reduction in cardiac readmissions at 12 months (P &lt; 0.01). The background group had no significant change in HADS score over time.ConclusionBrief CBT provided by cardiac nurses in relation to CR reduced anxiety and depression scores, improved HeartQoL and adherence to CR, and reduced cardiovascular readmissions. The programme is simple and may be implemented by CR nurses.
Technical comment on “sex ratios when helpers stay at the nest”
Authors: Wild Geoff 
Published: January 2023

AbstractI contributed a paper to volume 60 of the journal. The paper reported on my study of sex-ratio evolution when one sex (females) is helpful but the other sex (males) suffers less from kin competition. I had based my study on a kin-selection model, and so I was dismayed to discover an error in the relatedness calculations therein. Specifically, relatedness coefficients that should have been calculated using a sampling-without-replacement scheme were instead calculated using sampling with replacement. Here, I correct my error and show how it impacts my original findings. I argue that my main conclusions are unchanged. Furthermore, only two new findings contrast with those I presented earlier. First, changing those model details unrelated to the marginal fitness benefits of help does not, in turn, impact substantially the conflict that occurs between mates over the brood sex ratio (I had previously reported some noteworthy impact was possible). Second, help can reduce sex-ratio conflict between mates more effectively when breeders occur in smaller groups (previously, I had said this occurred in larger groups).
Whole Animal Feeding FLat (WAFFL): a complete and comprehensive validation of a novel, high-throughput fly experimentation system
Authors: Jaime Maria D L A , Salem Ghadi H , Martinez Daniel J , Karott Sean , Flores Alejandra , Palmer Cameron D , Mahadevaraju Sharvani , Krynitsky Jonathan , Garmendia-Cedillos Marcial , Anderson Sarah , Harbison Susan , Pohida Thomas J , Ludington William B , Oliver Brian 
Published: January 2023

Abstract
Non-mammalian model organisms have been essential for our understanding of the mechanisms that control development, disease, and physiology, but they are underutilized in pharmacological and toxicological phenotypic screening assays due to their low throughput in comparison with cell-based screens. To increase the utility of using Drosophila melanogaster in screening, we designed the Whole Animal Feeding FLat (WAFFL), a novel, flexible, and complete system for feeding, monitoring, and assaying flies in a high-throughput format. Our 3D printed system is compatible with inexpensive and readily available, commercial 96-well plate consumables and equipment. Experimenters can change the diet at will during the experiment and video record for behavior analysis, enabling precise dosing, measurement of feeding, and analysis of behavior in a 96-well plate format.
A polygenic basis for birth weight in a wild population of red deer (Cervus elaphus)
Authors: Gauzere Julie , Pemberton Josephine M , Slate Jon , Morris Alison , Morris Sean , Walling Craig A , Johnston Susan E 
Published: January 2023

Abstract
The genetic architecture of traits under selection has important consequences for the response to selection and potentially for population viability. Early QTL mapping studies in wild populations have reported loci with large effect on trait variation. However, these results are contradicted by more recent genome-wide association analyses, which strongly support the idea that most quantitative traits have a polygenic basis. This study aims to re-evaluate the genetic architecture of a key morphological trait, birth weight, in a wild population of red deer (Cervus elaphus), using genomic approaches. A previous study using 93 microsatellite and allozyme markers and linkage mapping on a kindred of 364 deer detected a pronounced QTL on chromosome 21 explaining 29% of the variance in birth weight, suggesting that this trait is partly controlled by genes with large effects. Here, we used data for more than 2,300 calves genotyped at &gt;39,000 SNP markers and two approaches to characterise the genetic architecture of birth weight. First, we performed a genome-wide association (GWA) analysis, using a genomic relatedness matrix to account for population structure. We found no SNPs significantly associated with birth weight. Second, we used genomic prediction to estimate the proportion of variance explained by each SNP and chromosome. This analysis confirmed that most genetic variance in birth weight was explained by loci with very small effect sizes. Third, we found that the proportion of variance explained by each chromosome was slightly positively correlated with its size. These three findings highlight a highly polygenic architecture for birth weight, which contradicts the previous QTL study. These results are probably explained by the differences in how associations are modelled between QTL mapping and GWA. Our study suggests that models of polygenic adaptation are the most appropriate to study the evolutionary trajectory of this trait.
Genomic Insights into the Population History of theResandeor Swedish Travelers
Authors: Vilà-Valls Laura , Aizpurua-Iraola Julen , Casinge Sebastian , Bojs Karin , Flores-Bello André , Font-Porterias Neus , Comas David 
Published: January 2023

AbstractThe Resande are a minority ethnic group in Sweden, who were characterized by an itinerant way of life, and they have been suggested to originate from the mixture between Swedish and Romani populations. Because the population history of the Resande has been scarcely studied, we analyzed genome-wide genotype array data from unrelated Resande individuals in order to shed light on their origins and demographic history for the first time from a genetic perspective. Our results confirm the Romani-related ancestry of this population and suggest an admixture event between a Romani-like population and a general Swedish-like population that occurred approximately between the mid-18th and mid-19th centuries, two centuries after the arrival of the first historically reported Romani families in Sweden. This inferred date suggests that the Romani group involved in the admixture is related to the pre-18th-century arrivals of Romani in Scandinavia. In addition, a reduction in the population size is detected previous to the admixture event, suggesting a subtle signal of isolation. The present work constitutes a step forward toward a better representation of ethnic minorities and underrepresented groups in population genetic analyses. In order to know in more detail the complete history of human populations, it is time to focus on studying populations that have not been previously considered for a general scenario and that can provide valuable information to fill in the gaps that still remain uncovered.
Epicutaneous Immunotherapy with CBir1 Alleviates Intestinal Inflammation
Authors: Chen Xin , Elson Charles O , Dunkin David 
Published: January 2023

Abstract

Background
Inflammatory bowel disease may be due to failed tolerance to normal gut bacteria. We demonstrate that epicutaneous immunotherapy (ET) to ovalbumin can alleviate colitis in murine models. However, most people are tolerant to or have anergy to ovalbumin. Half of Crohn’s disease (CD) patients have CBir1 antibodies that can be elevated years before CD development. We determined whether ET with a CBir1 multi-epitope peptide (MEP1) could alleviate colitis.

Methods
Wild type mice (C57BL/6) were transferred with CBir1 T cell receptor (TCR) T cells followed by epicutaneous application of MEP1. Proliferating Foxp3+ T cells were measured in mesenteric lymph nodes (LNs), spleen, small intestine, and colon by flow cytometry. Lymphocytes from MEP1 epicutaneously exposed and immunized C57BL/6 mice were cultured with MEP1. Interferon (IFN)-γ production was measured. Colitis was induced by transferring CD4+CD45Rbhi T cells from CBIR1 TCR or C57BL/6 mice into RAG1-/- mice. Mice were treated with ET. Body weight, colon length, colonic cytokine production, histological inflammation, inflammatory genes, and regulatory T cells (Tregs) from lamina propria were measured.

Results
ET with 10 μg of MEP1 induced CBir1-specific Tregs that migrated to the small intestine and colon and suppressed MEP1-specific IFN-γ production. ET alleviated colitis when the model utilized CBir1 TCR T cells in mice colonized with CBir1 or A4Fla2 positive bacteria. Treated mice had improved colon length and histological inflammation and reduced colonic IFN-γ production.

Conclusion
Epicutaneous immunotherapy with MEP1 induced Tregs that migrate to intestines and suppress inflammation in mice with CBir1 or A4Fla2-positive bacterial colonization. This could be a potential strategy to treat CD and warrants further study.
The microstructure of modularity in design: a design motif view
Authors: Brunswicker Sabine , Mukherjee Satyam 
Published: January 2023

Abstract
In their seminal theory on modularity in design, Baldwin and Clark (2000, Design Rules: The Power of Modularity. MIT Press) focus on the macro-level: They show that modularity limits the degree to which changes propagate throughout a complex system, as constituted by how interdependencies among all parts pattern into a nested design structure with shared parts at the top transmitting functionalities via central parts down to the bottom. In this paper, we shift the focus to the microlevel structures of interdependencies that reflect the local decisions of designers with limited rationality. Such decisions relate to five fundamental types of interdependence structures among three parts: the design motifs. Following Baldwin and Clark (2000, Design Rules: The Power of Modularity. MIT Press), we assume that value-seeking designers weigh costs and benefits when creating motifs. We develop a new design motif theory to understand the sources of macro-level modularity. We empirically explore this theory using a sample of more than 20,000 design structures of a complex software. We observe a stable, recurring design motif signature: high-value design motifs occur more frequently than low -alue ones because of each motif’s idiosyncratic microstructure. The common resource motif occurs most frequently because of its low costs and benefits for reliability in design. The sequential loop motif holds a critical role: it offers unique benefits for innovating system functionalities, but when placed in the center, it inflates the propagation of changes. This explains why central rather than shared parts are a potential source of innovation at the expense of modularity. These findings contribute to the research and practice of modularity in design.
Lifestyle, genetic risk and incidence of cancer: a prospective cohort study of 13 cancer types
Authors: Byrne Stephanie , Boyle Terry , Ahmed Muktar , Lee Sang Hong , Benyamin Beben , Hyppönen Elina 
Published: January 2023

Abstract

Background
Genetic and lifestyle factors are associated with cancer risk. We investigated the benefits of adhering to lifestyle advice by the World Cancer Research Fund (WCRF) with the risk of 13 types of cancer and whether these associations differ according to genetic risk using data from the UK Biobank.

Methods
In 2006–2010, participants aged 37–73 years had their lifestyle assessed and were followed up for incident cancers until 2015–2019. Analyses were restricted to those of White European ancestry with no prior history of malignant cancer (n = 195 822). Polygenic risk scores (PRSs) were computed for 13 cancer types and these cancers combined (‘overall cancer’), and a lifestyle index was calculated from WCRF recommendations. Associations with cancer incidence were estimated using Cox regression, adjusting for relevant confounders. Additive and multiplicative interactions between lifestyle index and PRSs were assessed.

Results
There were 15 240 incident cancers during the 1 926 987 person-years of follow-up (median follow-up = 10.2 years). After adjusting for confounders, the lifestyle index was associated with a lower risk of overall cancer [hazard ratio per standard deviation increase (95% CI) = 0.89 (0.87, 0.90)] and of eight specific cancer types. There was no evidence of interactions on the multiplicative scale. There was evidence of additive interactions in risks for colorectal, breast, pancreatic, lung and bladder cancers, such that the recommended lifestyle was associated with greater change in absolute risk for persons at higher genetic risk (P &lt; 0.0003 for all).

Conclusions
The recommended lifestyle has beneficial associations with most cancers. In terms of absolute risk, the protective association is greater for higher genetic risk groups for some cancers. These findings have important implications for persons most genetically predisposed to those cancers and for targeted strategies for cancer prevention.
Underascertainment of Respiratory Syncytial Virus Infection in Adults Due to Diagnostic Testing Limitations: A Systematic Literature Review and Meta-analysis
Authors: Onwuchekwa Chukwuemeka , Moreo Laura Mora , Menon Sonia , Machado Belen , Curcio Daniel , Kalina Warren , Atwell Jessica E , Gessner Bradford D , Siapka Mariana , Agarwal Neha , Rubbrecht Michelle , Nair Harish , Rozenbaum Mark , Aponte-Torres Zuleika , Vroling Hilde , Begier Elizabeth 
Published: January 2023

Abstract

Background
Most observational population-based studies identify respiratory syncytial virus (RSV) by nasal/nasopharyngeal swab reverse transcriptase real-time PCR (RT-PCR) only. We conducted a systematic review and meta-analyses to quantify specimen and diagnostic testing-based underascertainment of adult RSV infection.

Methods
EMBASE, PubMed, and Web of Science were searched (January 2000−December 2021) for studies including adults using/comparing &gt;1 RSV testing approach. We quantified test performance and RSV detection increase associated with using multiple specimen types.

Results
Among 8066 references identified, 154 met inclusion. Compared to RT-PCR, other methods were less sensitive: rapid antigen detection test (RADT; pooled sensitivity, 64%), direct fluorescent antibody (DFA; 83%), and viral culture (86%). Compared to singleplex PCR, multiplex PCR's sensitivity was lower (93%). Compared to nasal/nasopharyngeal swab RT-PCR alone, adding another specimen type increased detection: sputum RT-PCR, 52%; 4-fold rise in paired serology, 44%; and oropharyngeal swab RT-PCR, 28%. Sensitivity was lower in estimates limited to only adults (for RADT, DFA, and viral culture), and detection rate increases were largely comparable.

Conclusions
RT-PCR, particularly singleplex testing, is the most sensitive RSV diagnostic test in adults. Adding additional specimen types to nasopharyngeal swab RT-PCR testing increased RSV detection. Synergistic effects of using ≥3 specimen types should be assessed, as this approach may improve the accuracy of adult RSV burden estimates.