bluuebunny/crossref_metadata_2025 huggingface dataset:
IDEOM vitiligo work group: an update on our first year
Authors: Silverberg Nanette B , Cohen Arnon , Desai Seemal , Francis Priyanka , Francis Vimala , Gardner Jackie , Guarino Carrie , Guarino Isabella , Huang Victor , Rosmarin David ,   (Co-chair) [members are listed in alphabetical order]
Published: January 2023

The new Vitiligo Work Group of IDEOM was created in October 2021 and met at the annual IDEOM meetings of 2021 and 2022. The mission of the workgroup is to develop core outcome measures in vitiligo that meet three criteria: to meet the needs of stakeholders of all types, to be validated for clinical trials and studies, and to be used in all age groups of patients. The Vitiligo Work Group met November 2021 and June 2022, yielding a list of 10 potential core domains for voting. Voting was conducted at the Annual Meeting of IDEOM on 18 June 2022. Voting members of IDEOM included 23 dermatologists, 1 rheumatologist, 3 dermatologists and rheumatologists, 11 industry partners, 9 patients, 8 patient association representatives and 15 researchers. Core domains meeting 75% consensus threshold included: health-related quality of life (95·35%), extent of depigmentation (93·632%), treatment satisfaction including treatment burden (92·86%), location (83·67%), colour matching (82·69%) and maintenance of pigmentation (76·47%). Two domains met 50% threshold including primary diagnosis/comorbidities (59·62%) and trajectory of disease/stabilization (57·45%) and one domain, itch, failed to reach a consensus (38·46%). Using an approach of inclusion of stakeholders from all walks of life, six core domains reached a consensus for inclusion, two achieved partial consensus but required revision to break down the elements (e.g. primary diagnosis and comorbidities should be separated) and itch failed to achieve inclusion. The group continues to work on its core domains set using a broad range of stakeholders to produce a practical set of domains that are of importance to all stakeholders.
Co-producing Research with Disabled Lay Researchers: Lessons from a Project Exploring Social Workers’ Use of Digital Communication Technologies with Disabled Users of Social Work Services
Authors: Sarre Sophie , Meakin Becki , Geoghegan Luke , Robert Glenn , Sanders Charlie , Lavanchy Roxane , Minogue Shani , Fadden Tom , O’Brien Molly
Published: January 2023

The value of co-produced research is increasingly recognised. This is a case study of a lay conducted, co-produced qualitative research study on the experiences of social workers and Disabled users of their services of using (or not) digital technologies when communicating with each other. We describe the co-production process from inception to dissemination and draw out lessons for future studies. Disabled lay researchers developed interview topic guides, conducted semi-structured interviews with social workers and Disabled users of social work services, analysed the data and led or contributed to study outputs. Several factors contributed to the success of this study. It was co-produced using service user, practitioner and academic knowledge. It is built on existing trusted relationships. Training and support were targeted and relevant, and delivered using a variety of learning methods, including peer support. Disabled lay researchers drew on their lived experiences to develop topic guides and interpret data. The study team was committed to inclusion, capacity building and an assets-based approach, and to carefully managing power relationships. Challenges were the time required to setup the study and to train and support lay researchers, and the bureaucratic and governance systems that were not ideally suited to root and branch co-production.
Outcome of clinical experience of introducing a patient with secondary systemic AL-amyloidosis associated with multiple myeloma
Authors: Novosad Olga , Rudiuk Tymur , Shevchuk Lesya , Kundina Viktoriia , Schmidt Anna
Published: January 2023

This research is relevant, as AL-amyloidosis refers to a systemic type of disease characterized by aggregation of an improperly folded light chain of an immunoglobulin, mainly in the heart and kidneys, causing organ failure. This study describes the clinical experience of introducing a patient with cardiac amyloidosis associated with multiple myeloma (MM). A clinical case of a patient diagnozed with amyloidosis was considered. Magnetic resonance imaging signs of cardiac amyloidosis were confirmed due to the presence of concentric biventricular hypertrophy without dilation, atrial septal hypertrophy, a tendency to atrial dilation, thickening of valve flaps and atrial walls. Upon admission to the research institute, the patient had an anasarca. More accurate recognition of AL-amyloidosis by cardiologists allows for prescribing earlier treatment and improving results. Conventional treatment of MM and AL-amyloidosis includes a combination of dexamethasone with bortezomib and endoxan. Haematopoietic stem cell transplantation after taking high doses of melphalan has become another treatment option and has led to remission in some patients. The novelty of the study is that an example of a timely complete diagnosis and treatment of a combination of these two diseases was presented, as a result of which the patient has achieved a complete haematological and partial organ response to the underlying disease.
Exploring the emergence of morphological asymmetries around the brain’s Sylvian fissure: a longitudinal study of shape variability in preterm infants
Authors: De Vareilles Héloïse , Rivière Denis , Pascucci Marco , Sun Zhong-Yi , Fischer Clara , Leroy François , Tataranno Maria-Luisa , Benders Manon J , Dubois Jessica , Mangin Jean-François
Published: January 2023

Brain folding patterns vary within the human species, but some folding properties are common across individuals, including the Sylvian fissure’s inter-hemispheric asymmetry. Contrarily to the other brain folds (sulci), the Sylvian fissure develops through the process of opercularization, with the frontal, parietal, and temporal lobes growing over the insular lobe. Its asymmetry may be related to the leftward functional lateralization for language processing, but the time course of these asymmetries’ development is still poorly understood. In this study, we investigated refined shape features of the Sylvian fissure and their longitudinal development in 71 infants born extremely preterm (mean gestational age at birth: 26.5 weeks) and imaged once before and once at term-equivalent age (TEA). We additionally assessed asymmetrical sulcal patterns at TEA in the perisylvian and inferior frontal regions, neighbor to the Sylvian fissure. While reproducing renowned strong asymmetries in the Sylvian fissure, we captured an early encoding of its main asymmetrical shape features, and we observed global asymmetrical shape features representative of a more pronounced opercularization in the left hemisphere, contrasting with the previously reported right hemisphere advance in sulcation around birth. This added novel insights about the processes governing early-life brain folding mechanisms, potentially linked to the development of language-related capacities.
Sex differences and disparities in cardiovascular outcomes of COVID-19
Authors: Bugiardini Raffaele , Nava Stefano , Caramori Gaetano , Yoon Jinsung , Badimon Lina , Bergami Maria , Cenko Edina , David Antonio , Demiri Ilir , Dorobantu Maria , Fronea Oana , Jankovic Radmilo , Kedev Sasko , Ladjevic Nebojsa , Lasica Ratko , Loncar Goran , Mancuso Giuseppe , Mendieta Guiomar , Miličić Davor , Mjehović Petra , Pašalić Marijan , Petrović Milovan , Poposka Lidija , Scarpone Marialuisa , Stefanovic Milena , van der Schaar Mihaela , Vasiljevic Zorana , Vavlukis Marija , Vega Pittao Maria Laura , Vukomanovic Vladan , Zdravkovic Marija , Manfrini Olivia
Published: January 2023

Aims

Previous analyses on sex differences in case fatality rates at population-level data had limited adjustment for key patient clinical characteristics thought to be associated with coronavirus disease 2019 (COVID-19) outcomes. We aimed to estimate the risk of specific organ dysfunctions and mortality in women and men.

Methods and results

This retrospective cross-sectional study included 17 hospitals within 5 European countries participating in the International Survey of Acute Coronavirus Syndromes COVID-19 (NCT05188612). Participants were individuals hospitalized with positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from March 2020 to February 2022. Risk-adjusted ratios (RRs) of in-hospital mortality, acute respiratory failure (ARF), acute heart failure (AHF), and acute kidney injury (AKI) were calculated for women vs. men. Estimates were evaluated by inverse probability weighting and logistic regression models. The overall care cohort included 4499 patients with COVID-19-associated hospitalizations. Of these, 1524 (33.9%) were admitted to intensive care unit (ICU), and 1117 (24.8%) died during hospitalization. Compared with men, women were less likely to be admitted to ICU [RR: 0.80; 95% confidence interval (CI): 0.71–0.91]. In general wards (GWs) and ICU cohorts, the adjusted women-to-men RRs for in-hospital mortality were of 1.13 (95% CI: 0.90–1.42) and 0.86 (95% CI: 0.70–1.05; pinteraction = 0.04). Development of AHF, AKI, and ARF was associated with increased mortality risk (odds ratios: 2.27, 95% CI: 1.73–2.98; 3.85, 95% CI: 3.21–4.63; and 3.95, 95% CI: 3.04–5.14, respectively). The adjusted RRs for AKI and ARF were comparable among women and men regardless of intensity of care. In contrast, female sex was associated with higher odds for AHF in GW, but not in ICU (RRs: 1.25; 95% CI: 0.94–1.67 vs. 0.83; 95% CI: 0.59–1.16, pinteraction = 0.04).

Conclusions

Women in GW were at increased risk of AHF and in-hospital mortality for COVID-19 compared with men. For patients receiving ICU care, fatal complications including AHF and mortality appeared to be independent of sex. Equitable access to COVID-19 ICU care is needed to minimize the unfavourable outcome of women presenting with COVID-19-related complications.
Alternative polyadenylation regulation in cardiac development and cardiovascular disease
Authors: Cao Jun , Kuyumcu-Martinez Muge N
Published: January 2023

Cleavage and polyadenylation of pre-mRNAs is a necessary step for gene expression and function. Majority of human genes exhibit multiple polyadenylation sites, which can be alternatively used to generate different mRNA isoforms from a single gene. Alternative polyadenylation (APA) of pre-mRNAs is important for the proteome and transcriptome landscape. APA is tightly regulated during development and contributes to tissue-specific gene regulation. Mis-regulation of APA is linked to a wide range of pathological conditions. APA-mediated gene regulation in the heart is emerging as a new area of research. Here, we will discuss the impact of APA on gene regulation during heart development and in cardiovascular diseases. First, we will briefly review how APA impacts gene regulation and discuss molecular mechanisms that control APA. Then, we will address APA regulation during heart development and its dysregulation in cardiovascular diseases. Finally, we will discuss pre-mRNA targeting strategies to correct aberrant APA patterns of essential genes for the treatment or prevention of cardiovascular diseases. The RNA field is blooming due to advancements in RNA-based technologies. RNA-based vaccines and therapies are becoming the new line of effective and safe approaches for the treatment and prevention of human diseases. Overall, this review will be influential for understanding gene regulation at the RNA level via APA in the heart and will help design RNA-based tools for the treatment of cardiovascular diseases in the future.
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

In 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

Aim

PARADISE-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 results

Patients 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 <0.05 for all).

Conclusion

In 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

Background

Acute 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 summary

We 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.

Discussion

Considering 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

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

Aims

To 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 results

In 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 < 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 < 0.01), and a significant reduction in cardiac readmissions at 12 months (P < 0.01). The background group had no significant change in HADS score over time.

Conclusion

Brief 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

I 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

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

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 >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

The 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.
2. Clothes
Authors: Brassett James , Elias Juanita , Rethel Lena , Richardson Ben
Published: January 2023

This chapter discusses the topic of clothing in everyday international political economy (IPE). It begins by looking at how the garment industry and workers in that industry have been impacted by the Covid-19 pandemic, focusing in particular on the vulnerabilities faced by women workers in Leicester. This analysis introduces the concepts of fast fashion and commodity fetishism, and demonstrates how the globalization of garment production relates to the feminization of low-wage labour. The chapter then considers the broader politics of international trade that have shaped where in the world the production and disposal of clothing has been located. It also reviews efforts to reform the garment industry, including corporate social responsibility initiatives and the use of podcasting to highlight the under-researched topic of clothing disposal.
7. Social Media
Authors: Brassett James , Elias Juanita , Rethel Lena , Richardson Ben
Published: January 2023

This chapter explores the increasing significance of social media in international political economy (IPE). How we experience and represent social media has profound implications for the ethical possibilities and limits of global market life. The chapter begins by problematizing social media through the related concepts of self-branding, the attention economy, and the prosumer. It then looks at social media via two popular documentaries on Netflix: Fyre: The Greatest Party That Never Happened (2018) and The Social Dilemma (2020). These documentaries tackle questions of reform and regulation, identifying how social media data carries immense value for corporate marketing, political strategy, credit rating, and other ways of knowing and governing society. This helps to establish an important dilemma: is social media a free and democratic space or a new infrastructure of surveillance? Finally, the chapter reflects on the politics of social media by considering different forms of critical agency.
Epicutaneous Immunotherapy with CBir1 Alleviates Intestinal Inflammation
Authors: Chen Xin , Elson Charles O , Dunkin David
Published: January 2023

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

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

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 < 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

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 >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.
A New Broad-Spectrum Drug Screen for 127 Analytes by LC-MS/MS
Authors: Smith Kathryn , Johnson-Davis Kamisha L , Shahrokh Kiumars
Published: January 2023

Background

Broad-spectrum drug screening is offered by many clinical laboratories to support investigation of possible drug exposures. The traditional broad-spectrum drug screen employed at our laboratory utilizes several different analytical platforms, thus requiring relatively high volumes of sample and a cumbersome workflow. Here we describe the development and validation of a consolidated broad-spectrum drug screen assay designed to qualitatively detect 127 compounds in urine (Ur) and serum/plasma (S/P) samples.

Methods

An LC-MS/MS method was developed using the Ultivo LC-MS/MS and designed to be qualitative with a 1-point calibration curve and 50% to 150% controls. Sample preparation included the addition of 122 internal standards (IS) followed by mixed-mode strong cation exchange solid-phase extraction and reverse-phase chromatographic separation on a biphenyl column.

Results

For the method described herein, ≥ 95% of analytes in urine and serum control samples had a CV of ≤20% for total imprecision. Accuracy testing included 46 external controls and demonstrated 99.9% accuracy. Method comparison studies to quantitative testing are discussed. The high level of coverage of the analytes with a stable isotope-labeled IS (SIL-IS) helped normalize for matrix effects when significant ion suppression (>25%) was present. Analyte stability in the matrix, the impact of potentially interfering compounds, and method ruggedness were demonstrated. Method limitations include limited detection of glucuronidated drugs and potential cross-contamination with samples at very high concentrations (>>100 × cutoff).

Conclusions

The broad-spectrum drug screen method developed here qualitatively detected 127 drugs and select metabolites. This method could be used to support investigations of possible drug exposures in a clinical setting.
Application of the three-component transient electromagnetic method in gold exploration: a case study of the Heicigou gold deposit in east Kunlun
Authors: Wang Xingchun , Zhi Qingquan , Deng Xiaohong , Wu Junjie , Zhang Jie , Yu Zhonghong , Yang Yi
Published: January 2023

Heicigou gold mine is a gold polymetallic mine controlled by a northwest trending fault. The magnetic method and induced polarization results show that the gold-bearing alteration zone is distributed discontinuously in a northwest direction, but the spatial distribution characteristics of the alteration zone have not been effectively identified. Although some drilling work has been carried out in the latter, the number and the depths of the drillings have been insufficient to control the distribution of the alteration zone. According to the measured three-component transient electromagnetic anomaly characteristics, we designed corresponding models and carried out three-component forward simulation on the platform of EMIT Maxwell. We summarized the corresponding relationship between the three-component plane change characteristics and the orientation and occurrence of the low-resistivity medium subsurface. We applied this method to the Heicigou gold deposit and found that the occurrence of the ore-bearing alteration zone is northeast. This discovery solved the problem that the previous magnetic method and induced polarization method failed to solve. It corrected the geologists’ incorrect understanding of the spatial distribution of the alteration zone.
Petrophysical characteristics and identification parameters of the Jurassic continental shale oil reservoirs in the Central Sichuan Basin
Authors: Song Yichen , Zeng Lianbo , Gong Fei , Huang Ping , Lyu Wenya , Dong Shaoqun
Published: January 2023

The Sichuan Basin in south-western China is rich in shale oil in the Jurassic strata. Due to its complex geological characteristics, reservoir identification using current log-constrained seismic inversion methods is difficult. Characteristics of the shale oil reservoirs were tested on the basis of the petrophysical experimentation of core samples from the said strata. Thin sections and logging data analysis showed the influencing factors on petrophysical characteristics and clarified the sensitive geophysical parameters for reservoir identification. The Da'anzhai Member reservoirs were determined to have high acoustic velocities, Vp/Vs ratios and Young's moduli, and low Poisson's ratios. Several geological factors have influenced the petrophysical properties of the reservoirs. The Da'anzhai Member reservoirs are characterized by a low content of clay minerals and the development of fractures and laminae. The presence of clay minerals caused general high acoustic velocities of the reservoirs; the presence of fractures and laminae in high-quality reservoirs results in a decrease of the acoustic velocities. Therefore, the relatively low value against the background of high acoustic velocity can be used as the criteria for high-quality reservoirs. Poisson's ratio is obviously different in reservoirs and non-reservoirs. When it is <0.269, the reservoirs can be fully identified. In addition, the combination of the Lame constant and shear modulus (λ > 25.277 and μ > 20.72 GPa), P-wave and S-wave velocity (Vp > 4967 and Vs > 2781 m s−1), wave impedance and Vp/Vs ratio (AI > 13.319 g · cm3 · km · s−1 and Vp/Vs > 1.792) can also provide references for reservoir identification.
A lithofacies prediction method based on stochastic simulation
Authors: Li Jingnan , Sun Zhentao , Liu Chanjuan , Zhu Tong , Cao Huilan , Li Feifei
Published: January 2023

Lithofacies prediction can facilitate the search for hydrocarbon reservoirs and is, therefore, crucial for seismic exploration. We proposed a new approach for lithofacies prediction based on stochastic simulation of pseudo-wells. First, we performed a pseudo-well simulation using a continuous-time Markov chain (CTMC), which can accurately describe geological deposition and can be created using logging, core or geological data. We used the CTMC to randomly generate many pseudo-wells with different lithofacies columns. The corresponding reservoir and elasticity parameters for these lithofacies columns were determined using the Monte Carlo random sampling method. Second, we used seismic modeling and seismic matching to predict the lithofacies. We applied the elastic parameters for each pseudo-well to calculate the reflection coefficients and performed seismic modeling to generate synthetic seismic data. Thereafter, we used a weighted matching function based on prior geological constraints to match the synthetic seismic data with actual seismic data. We predicted the lithofacies based on numerous pseudo-wells with the best fit and tested the influencing factors of the method using model data. Finally, we applied this method to the field data, and the predicted lithofacies agreed well with the wells. Compared to conventional methods, the proposed method can use prior information in the log and the geology data, and detects thin layers better.
Exploring how cultural and structural elements relate to communal coping for separated Latina/o/x immigrant families
Authors: Mendez Murillo Roselia , Kam Jennifer A
Published: January 2023

Family immigration-related separation is incredibly stressful; however, Latina/o/x separated families might engage in communal coping to help mitigate those stressors. Utilizing the extended theoretical model of communal coping, we conducted semi-structured interviews with 20 family triads (i.e., separated parent, separated child, primary caregiver) who were experiencing or had recently experienced immigration-related family separation. We explored cultural and structural elements associated with communally or individually coping, and we considered why family members, all of whom experienced separation stress, might cope differently. Among the different types of family members, gender norms were related to communally coping, relying on extended family for support, and protective buffering. Physical distance, as well as limited technology access and literacy also hindered communal coping. When exploring within-family-triad experiences, three themes were apparent: (a) one-sided communal coping, (b) protective buffering at the cost of one’s own needs, and (c) communal coping impeded by relational strain. Our findings emphasize the importance of considering the multidimensional nature of a stressor (i.e., family separation) when determining whether people are communally coping; how cultural and structural elements relate to coping; and including multiple family members’ perspectives.
Postoperative transverse colon necrosis due to mesenteric injury during laparoscopic surgery for endometrial carcinoma
Authors: Kaji Kentaro , Tsubouchi Hirofumi , Mori Masahiko , Suzuki Shiro
Published: January 2023

Hemorrhage and organ injury have been frequently reported as complications associated with trocar puncture in laparoscopic surgery. This report presents a case of delayed intestinal necrosis due to mesenteric injury. A 76-year-old woman who had a history of distal gastrectomy and adrenal insufficiency was diagnosed with stage IA endometrial cancer. We performed laparoscopic total hysterectomy and bilateral salpingo-oophorectomy. The upper abdominal wall and mesentery were adhered, and bleeding from the mesentery was noted during the first trocar puncture of the umbilical region, resulting in ligation and hemostasis. Abdominal pain and fever developed on the third postoperative day, and contrast-enhanced computed tomography demonstrated transverse colon perforation. Emergency laparotomy showed necrosis in the proximal transverse colon and a defect in the marginal artery. Mesenteric injury can lead to delayed intestinal necrosis without intraoperative macroscopic findings. In laparoscopic cases where adhesion is expected, trocar placement should be carefully considered.
Traumatic spigelian hernia complicated by caecal perforation and retroperitoneal haematoma—an unusual concurrence in blunt trauma
Authors: Syed Faisal , Quah Gaik si , Di Re Angelina
Published: January 2023

Blunt abdominal injury can be a cause of significant morbidity and mortality in patients who have sustained trauma even at low velocity. We report on an unusual case of a 50-year-old male who developed a traumatic spigelian hernia and caecal perforation after falling off a pushbike and impacting on the handlebar. We have also discussed some of the considerations taken in the assessment and surgical management of this case.