bluuebunny/crossref_metadata_2025 huggingface dataset:
O099 A relevant metabolic model for monitoring human metabolism in vivo using dynamic nuclear polarization with 13C magnetic resonance spectroscopy
Authors: Torchi J , Mallinson A , Cooper D , Auer P , Morris P , Lobo D N , Greenhaff P L , Serres S
Published: May 2023

Introduction

DNP increases the signal of carbon-13 molecules on MR scans (>10,000-fold), enabling real-time, dynamic quantitation of tissue metabolism in vivo with significant clinical potential. 13C quantification of metabolism is affected by confounding factors (T1 signal decay, flip angle, and metabolite escape), which necessitates metabolic modelling. Here, we have assessed a mathematical model that requires minimal information on confounding factors to measure metabolic rates with reliability.

Methods

Four healthy male volunteers (age; 24 ± 1.4 years; BMI; 23 ± 0.4 kg/m2) were recruited. Sterile hyperpolarized 13C pyruvate was safely produced using a clinical DNP polariser (SPINlab GE-Healthcare) and administered intravenously to volunteers performing in-bore plantar-flexion exercise to increase muscle pyruvate flux. 13C MR scans of the calf muscle were collected during exercise and used to test our model against 5000 computer simulations using randomised kinetic constants and confounding factors.

Results

The signal of metabolites was used to extract the kinetic constants of hyperpolarised-13C pyruvate conversion to lactate (KpL), alanine (KpA), and bicarbonate (KpB) with reproducibility and satisfactory signal-to-noise ratio (8.2 ± 1.8×102 s−1, 2.3 ± 2.1×102 s−1 to 2.1 ± 1.3 x103 s−1, respectively; mean ± SD). Model predictions were in statistical agreement with the kinetic constants used in the simulations.

Conclusion

Our metabolic model could be used to measure metabolic conversion of hyperpolarised-13C metabolites in the context of surgery, where postoperative insulin resistance is well-known to be linked to stress-induced upregulation of pyruvate dehydrogenase inhibitor.
O100 The effect of acidosis on contractility induced in porcine splanchnic arteries by clonidine or noradrenaline
Authors: Skorepa P , Lobo D N , Wilson V
Published: May 2023

Introduction

Clonidine, through its agonist action on central α2-adrenoceptors, is increasingly being used to induce sedation in critically ill patients with persistent acidosis and impaired renal function. Since it is also known to exert cardiovascular effects via peripheral α2-adrenoceptors, we compared its vasoconstrictor activity in porcine isolated arteries at different pH, to that produced by noradrenaline.

Methods

Isometric tension recordings of porcine isolated mesenteric, splenic and renal arteries (2mm internal diameter) were conducted in modified Krebs-Henseleit solution containing 105mM chloride ions maintained at pH 7.2 and 7.4 (modification of bicarbonate and chloride ions with gluconate ions). The potency of clonidine and noradrenaline was assessed by the pD2 (logarithm of concentration causing 50% of maximum response).

Results

Clonidine elicited concentration-dependent contractions in the renal artery (pD2 - 7.25±0.09 and 7.10±0.10, n=9) and splenic artery (pD2 - 6.81±0.09 and 7.02±0.06, n=8) that were not altered by a reduction in pH from 7.4 to 7.2 (p >0.05 paired Student's t-test). Clonidine failed to elicit consistent responses in the mesenteric artery (< 10% 60mM KCl). In contrast, the maximum response and potency to noradrenaline in the mesenteric artery (226.6±24.6% and pD2 5.43±0.11, n=6) was significantly reduced (p <0.05) by pH 7.2 (174.4±13.3% and pD2 5.13±0.11, n=6). Responses to noradrenaline in the renal and splenic artery were not affected by changes in pH.

Conclusion

Acidosis impairs the peripheral vascular actions of the non-selective α-adrenoceptor agonist noradrenaline more than those elicited by the selective α2-adrenoceptor agonist clonidine.
O101 Mitochondrial P53 inhibition ameliorates acute pancreatitis through reduction of mitochondrial injury and cell necrosis
Authors: Awais M , Cai W , Latawiec D , Mukherjee R , Chvanov M , Tepikin A , Criddle D , Sutton R
Published: May 2023

Introduction

Persistent opening of the mitochondrial permeability transition pore (MPTP) is central to acute pancreatitis (AP). Mitochondrial translocation of P53 promotes MPTP opening, which induces necrotic cell death. We sought to determine whether and how mitochondrial P53 inhibition is protective in experimental AP.

Methods

Mitochondrial translocation of P53 was inhibited by pifithrin-mu (PFT-µ, mitochondrial specific P53 inhibitor) or by Trp53 KO. Mitochondrial membrane potential (ΔΨm) and necrosis of murine pancreatic acinar cells (PACs) were evaluated by confocal microscopy with TMRM and propidium iodide, respectively, in the presence of TLCS. Fluo4 was used for calcium imaging. Caerulein AP (Cer-AP) was induced in male (WT, P53−/+, P53−/−; 10-12 week old) mice by 7 hourly i.p. injections of 50 μg/kg caerulein. PFT-µ (5 mg/kg) was injected after the third injection of caerulein; sacrifice was made 12h after the first injection of caerulein. AP was assessed by standard biomarkers and blinded histopathology.

Results

TLCS-induced collapse of ΔΨm and cell necrosis of wild type PACs were significantly reduced in the presence of PFTµ or in PACs isolated from Trp53 KO mice; calcium overload was also reduced, indicative of improved calcium clearance, and ATP was maintained. Pharmacological or genetic P53 inhibition resulted in significant reductions of biochemical, immunological, and histopathological indices of severity in the Cer-AP model.

Conclusion

Inhibition of P53 maintained mitochondrial integrity, reduced PACs necrosis, and ameliorated the severity of Cer-AP. These data suggest that inhibition of mitochondrial translocation of P53 could be an effective strategy for the treatment of AP.
O117 Burosumab in the management of X-linked hypophosphataemia: a retrospective cohort study reviewing anthropometric and biochemical markers
Authors: Walker E , Lindsay T , Allgrove J , Marlais M , Bockenhauer D , Hayes W
Published: May 2023

Introduction

Rickets is a bone disease caused by a defect in mineralization. When left untreated, it has lifelong Orthopaedic sequelae. Burosumab, an anti-fibroblast growth factor 23 monoclonal antibody, improves rickets severity, symptoms, and growth in children with X-linked hypophosphataemia (XLH) followed to 64 weeks in clinical trials. International dosing guidance recommends targeting normal serum phosphate concentration. However, some children may not achieve this despite maximal dosing. This study compares clinical outcomes in children with XLH on long-term burosumab treatment who achieved normal phosphate, vs those who did not.

Methods

Single-centre retrospective review of a large paediatric cohort with XLH treated with burosumab. We evaluated growth and biochemical markers of bone health in those who did compared to those who did not achieve normal plasma phosphate concentration.

Results

Fifty-five children with XLH with median age 11.7 [6.8–15.5] years were included. 27 (49%) had low plasma phosphate concentration, and 27 (49%) normal phosphate after a median burosumab treatment duration of 3.3 [IQR 2.6–3.7] years. 1 (2%) did not have a recent phosphate level recorded. No difference in growth was found between normal and abnormal phosphate groups (p = 0.9). A trend of superior growth in those with normal compared with abnormal alkaline phosphatase level was observed.

Conclusion

Young children with XLH experience sustained growth on long-term burosumab treatment, albeit without normal plasma phosphate concentration in many. Consideration should be made to changing burosumab dosing recommendations to target the normalisation of alkaline phosphatase instead of plasma phosphate concentration.
O123 Significance of hepatitis A virus cellular receptor-1 (HAVCR1) and its association with tumour immune microenvironment in breast cancer
Authors: Cao X S , Cong B B , Jiang W G , Martin T A
Published: May 2023

Introduction

Immunotherapy has an important role in the intervention of breast cancer, but single-agent efficacy of immunotherapy is poor, owing in part to influence of the surrounding tumour microenvironment. Hepatitis A virus cellular receptor-1 (HAVCR1), plays vital roles in immune microenvironment in pancreatic adenocarcinoma, but not clear in breast cancer. The present study aimed to characterize the role of HAVCR1 in immune microenvironment of breast cancer.

Methods

The Cancer Genome Atlas was used to evaluate functional role of HAVCR1. Kaplan-Meier plotter and Tumor Immune Estimation Resource were applied to illustrate correlation of HAVCR1 with the prognosis and immune infiltration of breast cancer.

Results

In Pietenpol subtype, high HAVCR1 levels indicated a favourable overall survival (OS) (HR=0.08, 95%CI:0.01-0.61, P=0.0024) in mesenchymal stem–like breast cancer. However, it was connected to worse OS (HR=2.29, 95%CI:1.04-5.04, P=0.035) in immunomodulatory subtype. Significant correlation was found between HAVCR1 expression level and immune infiltration in breast cancer, especially with B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils and Dendritic cell (P<0.05), and other immune markers, such as PDCD1 and CTLA4 (P<0.05). Decreased of HAVCR1 in Mesenchymal stem cells, Natural killer T-cells and enriched of B cell, CD4+ memory T-cells, CD8+ T-cells, Type 1 T-helper cells, Type 2 T-helper cells significantly improved the prediction of OS (P<0.05). Decreased impression of HAVCR1 in B cells and CD8+ T-cells were correlated with worse OS (P<0.05).

Conclusion

HAVCR1 is closely correlated with immune microenvironment and may serve as a potential tumour immunotherapy target for breast cancer.
O129 Patient satisfaction with long-term sacral neuromodulation for faecal incontinence: experience from a single tertiary centre
Authors: Martin S A , O'Connor A D , Selvakumar D , Baraza W , Faulkner G , Mullins D , Kiff E S , Telford K J , Sharma A
Published: May 2023

Introduction

Sacral neuromodulation is an established intervention for faecal incontinence (FI). This investigation aimed to determine the relationship between patient satisfaction and (1) device status (active/inactive) and (2) long-term functional outcomes.

Methods

Patients treated with sacral neuromodulation for at least 5 years reported bowel habits, FI severity, and impact on quality of life via bowel diaries, St. Marks incontinence score, and the Manchester Health Questionnaire at baseline and follow-up. On all measures, lower scores represent favourable outcomes. Satisfaction since treatment initiation and over the preceding 2 weeks was assessed using visual analogue scales (0%-100%). Individuals with inactive devices were awaiting battery revision surgery due to service delays encountered during the COVID-19 pandemic.

Results

In total, 74/110 eligible individuals completed follow-up measures (median: 130 months). Median overall satisfaction was high at 80% (IQR:60%-95%, n=70). Median two-week satisfaction was 75% (IQR:40%-90%, n=50) for individuals with active devices, and 20% (IQR:0%-45%, n=17) for those with inactive devices. Between-group differences were significant for two-week satisfaction (p<0.001), but not overall satisfaction (p=0.114). Two-week satisfaction was negatively correlated with all outcome measures (FI episodes: -0.46, faecal urgency episodes: -0.52, St. Marks incontinence score: -0.68, Manchester Health Questionnaire: -0.62 [all p<0.001]). However, of 12 individuals with active devices who did not meet the conventional treatment success threshold (50% FI reduction), 4 still reported ≥80% two-week satisfaction.

Conclusion

Standardised outcome measures reflect subjective satisfaction but cannot be used alone to assess positive outcomes as perceived by patients. Timely device revision is imperative for continued success of treatment.
O158 Telephone post-operative follow-ups can be safely used for thyroidectomy and parathyroidectomy patients
Authors: Charakopoulou A , Zahari F , Tunstall L , Carvell J , Wheatley S , Ketton L , Adeleye A , Bintichedin N , Chadwick D , Christakis I
Published: May 2023

Introduction

The aim of this study was to implement and evaluate the efficiency of telephone post-operative follow-ups (TFUs) in an Endocrine Surgical Unit.

Methods

Patients operated [thyroidectomy (Tx) or parathyroidectomy (PTx)] in the Department of Endocrine Surgery between 6/2019 and 1/2021 were included in this study. Patients with a cancer diagnosis on histology were automatically converted to a clinic appointment.

Results

155 patients were included. There were 75 and 80 patients with a Tx or a PTx operation respectively. The mean age for Tx and PTx patients was 50 (SD:17) and 56 (SD:15) respectively. The male/female ratio for Tx and PTx patients was 1:5. and 1:4 respectively. The main indication for an operation was Thy3a/f tumour and PHPT. The mean hospital stay for Tx and PTx patients was 1.3 (SD:1.5) and 1.2 (SD:0.9) days respectively. The % of patients discharged back to the GP after the 1st TFU was 50% and 46% for Tx and PTx patients respectively. 15% and 8% of Tx and PTx patients respectively required a 3rd FU. 8%, and 5% of Tx and PTx patients respectively required a conversion a subsequent clinic appointment. The mean (SD) distance of the patient's residence from hospital was 16 km (SD:25) and 23 km (SD: 20) for Tx and PTx patients respectively. There were no complaints from the patients in this study.

Conclusion

Post-operative TFUs are suitable for patients undergoing a Tx and/or PTx. A small percentage of patients will require conversion to a face-to-face clinic follow-up.
O163 The secretome of adipose-derived stem cells (ADSCS): exploring anti-fibrotic effects in skin fibrosis
Authors: Frommer M , Abu-Hanna J , Awad L , Langridge B , Butler P
Published: May 2023

Introduction

As part of surgical reconstruction with autologous fat grafting, ADSCs are believed to play a pivotal role in the observed anti-fibrotic effect, however, the exact mechanisms remain unknown. Here, we explored the changes in the ADSC secretome after proinflammatory and profibrotic stimulation in-vitro to gain further mechanistic insights.

Methods

ADSCs were obtained from five non-obese patients (BMI<30) without systemic disease (n=5). ADSCs were exposed to either TGF-β1, IL-1β, hypoxia (1%O2) or 10% fetal bovine serum (FBS) for 24 hours. 0.1%FBS was used as control group. Samples were then analysed by RT-qPCR for nine target genes. Selected targets were validated in the secretome through ELISA. Further, expression of surface markers was explored by RT-qPCR.

Results

VEGF, FGF2, CSF1, and CCN5 were explored at protein level. VEGF secretion increased significantly in all treatment groups. IL-1β significantly increased the production of FGF2 at protein level (p=0.043). CSF1 was secreted in similar amounts across groups. CCN5 secretion varied little, although higher amounts were detected in the 10%FBS group. Hypoxia and IL-1β increased expression of ADSC markers (CD90, CD73, CD26), while TGF-β1 and 10%FBS decreased it. However, CD105 was upregulated in the 10%FBS group. Additionally, TIMP1, MMP2, APP, and OGN were explored.

Conclusion

ADSCs secreted VEGF, FGF2, CCN5, and CSF1 in an in-vitro fibrotic environment. Further investigation of these pathways may lead to the development of novel treatments for fibrotic diseases such as scleroderma and radiation-induced fibrosis.
Where have prions been all our lives?
Authors: Minikel Eric Vallabh , Vallabh Sonia M
Published: May 2023

This scientific commentary refers to ‘Seed amplification and neurodegeneration marker trajectories in individuals at risk of prion disease’ by Mok et al. (https://doi.org/10.1093/brain/awad101).
Assessing chronic stress in wild mammals using claw-derived cortisol: a validation using European badgers (Meles meles)
Authors: Fokidis H Bobby , Brock Taylor , Newman Chris , Macdonald David W , Buesching Christina D
Published: May 2023

Measuring stress experienced by wild mammals is increasingly important in the context of human-induced rapid environmental change and initiatives to mitigate human-wildlife conflicts. Glucocorticoids (GC), such as cortisol, mediate responses by promoting physiological adjustments during environmental perturbations. Measuring cortisol is a popular technique; however, this often reveals only recent short-term stress such as that incurred by restraining the animal to sample blood, corrupting the veracity of this approach. Here we present a protocol using claw cortisol, compared with hair cortisol, as a long-term stress bio-indicator, which circumvents this constraint, where claw tissue archives the individual’s GC concentration over preceding weeks. We then correlate our findings against detailed knowledge of European badger life history stressors. Based on a solid-phase extraction method, we assessed how claw cortisol concentrations related to season and badger sex, age and body-condition using a combination of generalized linear mixed models (GLMM) (n = 668 samples from 273 unique individuals) followed by finer scale mixed models for repeated measures (MMRM) (n = 152 re-captured individuals). Claw and hair cortisol assays achieved high accuracy, precision and repeatability, with similar sensitivity. The top GLMM model for claw cortisol included age, sex, season and the sex*season interaction. Overall, claw cortisol levels were significantly higher among males than females, but strongly influenced by season, where females had higher levels than males in autumn. The top fine scale MMRM model included sex, age and body condition, with claw cortisol significantly higher in males, older and thinner individuals. Hair cortisol was more variable than claw; nevertheless, there was a positive correlation after removing 34 outliers. We discuss strong support for these stress-related claw cortisol patterns from previous studies of badger biology. Given the potential of this technique, we conclude that it has broad application in conservation biology.
Ocean warming favours a northern Argyrosomus species over its southern congener, whereas preliminary metabolic evidence suggests that hybridization may promote their adaptation
Authors: Pringle Brett A , Duncan Murray I , Winkler Alexander C , Mafwila Samuel , Jagger Charmaine , McKeown Niall J , Shaw Paul W , Henriques Romina , Potts Warren M
Published: May 2023

Anthropogenic-induced climate change is having profound impacts on aquatic ecosystems, and the resilience of fish populations will be determined by their response to these impacts. The northern Namibian coast is an ocean warming hotspot, with temperatures rising faster than the global average. The rapid warming in Namibia has had considerable impacts on marine fauna, such as the southern extension of the distribution of Argyrosomus coronus from southern Angola into northern Namibian waters, where it now overlaps and hybridizes with the closely related Namibian species, A. inodorus. Understanding how these species (and their hybrids) perform at current and future temperatures is vital to optimize adaptive management for Argyrosomus species. Intermittent flow-through respirometry was used to quantify standard and maximum metabolic rates for Argyrosomus individuals across a range of temperatures. The modelled aerobic scope (AS) of A. inodorus was notably higher at cooler temperatures (12, 15, 18 and 21°C) compared with that of A. coronus, whereas the AS was similar at 24°C. Although only five hybrids were detected and three modelled, their AS was in the upper bounds of the models at 15, 18 and 24°C. These findings suggest that the warming conditions in northern Namibia may increasingly favour A. coronus and promote the poleward movement of the leading edge of their southern distribution. In contrast, the poor aerobic performance of both species at cold temperatures (12°C) suggests that the cold water associated with the permanent Lüderitz Upwelling Cell in the south may constrain both species to central Namibia. This is most concerning for A. inodorus because it may be subjected to a considerable coastal squeeze.
CaviDB: a database of cavities and their features in the structural and conformational space of proteins
Authors: Velez Rueda Ana Julia , Bulgarelli Franco Leonardo , Palopoli Nicolás , Parisi Gustavo
Published: May 2023

Proteins are the structural, functional and evolutionary units of cells. On their surface, proteins are shaped into numerous depressions and protrusions that provide unique microenvironments for ligand binding and catalysis. The dynamics, size and chemical properties of these cavities are essential for a mechanistic understanding of protein function. Here, we present CaviDB, a novel database of cavities and their features in known protein structures. It integrates the results of commonly used cavity detection software with protein features derived from sequence, structural and functional analyses. Each protein in CaviDB is linked to its corresponding conformers, which also facilitates the study of conformational changes in cavities. Our initial release includes ∼927 773 distinct proteins, as well as the characterization of 36 136 869 cavities, of which 1 147 034 were predicted to be drug targets. The structural focus of CaviDB provides the ability to compare cavities and their properties from different conformational states of the protein. CaviDB not only aims to provide a comprehensive database that can be used for various aspects of drug design and discovery but also contributes to a better understanding of the fundamentals of protein structure–function relationships. With its unique approach, CaviDB represents an indispensable resource for the large community of bioinformaticians in particular and biologists in general.

Database URL https://www.cavidb.org
MantaID: a machine learning–based tool to automate the identification of biological database IDs
Authors: Zeng Zhengpeng , Hu Jiamin , Cao Miyuan , Li Bingbing , Wang Xiting , Yu Feng , Mao Longfei
Published: May 2023

The number of biological databases is growing rapidly, but different databases use different identifiers (IDs) to refer to the same biological entity. The inconsistency in IDs impedes the integration of various types of biological data. To resolve the problem, we developed MantaID, a data-driven, machine learning–based approach that automates identifying IDs on a large scale. The MantaID model’s prediction accuracy was proven to be 99%, and it correctly and effectively predicted 100,000 ID entries within 2 min. MantaID supports the discovery and exploitation of ID from large quantities of databases (e.g. up to 542 biological databases). An easy-to-use freely available open-source software R package, a user-friendly web application and application programming interfaces were also developed for MantaID to improve applicability. To our knowledge, MantaID is the first tool that enables an automatic, quick, accurate and comprehensive identification of large quantities of IDs and can therefore be used as a starting point to facilitate the complex assimilation and aggregation of biological data across diverse databases.
Genome sequence and salinity adaptation of the desert shrub Nitraria sibirica (Nitrariaceae, Sapindales)
Authors: Ma Xiaohui , Ru Dafu , Morales-Briones Diego F , Mei Fengyuan , Wu Jingjing , Liu Jianquan , Wu Shengdan
Published: May 2023

The genetic bases of halophytes for salinity tolerance are crucial for genetically breeding salt-tolerant crops. All natural Nitrariaceae species that exclusively occur in arid environments are highly tolerant to salt stress, but the underlying genomic bases to this adaptation remain unknown. Here we present a high-quality, chromosome-level genome sequence of Nitraria sibirica, with an assembled size of 456.66 Mb and 23,365 annotated genes. Phylogenomic analyses confirmed N. sibirica as the sister to all other sampled representatives from other families in Sapindales, and no lineage-specific whole-genome duplication was found except the gamma triplication event. Still, we found that the genes involved in K+ retention, energy supply, and Fe absorption expanded greatly in N. sibirica. Deep transcriptome analyses showed that leaf photosynthesis and cuticular wax formation in roots were enhanced under salt treatments. Furthermore, many transcription factors involved in salt tolerance changed their expressions significantly and displayed tissue- and concentration-dependent signalling in response to salt stress. Additionally, we found vacuolar Na+ compartmentalization is an ongoing process under salt treatment, while Na+ exclusion tends to function at high salt concentrations. These genomic and transcriptomic changes conferred salt tolerance in N. sibirica and pave the way for the future breeding of salt-tolerant crops.
Assessment of Stool DNA Markers to Detect Colorectal Neoplasia in Patients with Inflammatory Bowel Disease: A Multi-site Case-control Study
Authors: Itzkowitz Steven , Farraye Francis A , Limburg Paul J , Gagrat Zubin , Olson Marilyn C , Zella Julia , Kisiel John B
Published: May 2023

Background and Aims

The FDA-approved multitarget stool-DNA [mt-sDNA] test is a successful colorectal cancer [CRC] screening tool in average-risk individuals but is not indicated for patients with inflammatory bowel disease [IBD]. We determined the performance of the mt-sDNA assay without the haemoglobin component [mt-sDNAHgb-] in patients with IBD, while measuring sensitivity for colorectal cancer and advanced colorectal neoplasia [ACRN].

Methods

This was a multi-centre, proof-of-concept investigation in persons aged 18–84 years with a diagnosis of IBD, or primary sclerosing cholangitis [PSC] with IBD. Enrolment occurred between March 2013 and May 2016. Stool was tested with the mt-sDNA molecular markers only, minus the immunochemical haemoglobin component.

Results

The analysis set contained 355 samples. The median age was 52 [range 39–62] years, 45.6% were female and 93% were White. Two-thirds [63%] had ulcerative colitis [UC] and 10.1% had PSC/IBD. Colonoscopy revealed cancer in 8.5% [N = 30], advanced precancerous lesions [APLs] in 9.3% [N = 33] and non-advanced precancerous lesions in 7.6% [N = 27], and three-quarters [74.7%, N = 265] had negative findings. mt-sDNAHgb- sensitivity was 73.3% for any stage cancers, and 76.2% for ACRN. Sensitivity was highest for IBD-associated high-grade dysplasia at 100% and 84.6% for IBD-associated low-grade dysplasia ≥1 cm. The test showed higher sensitivity and lower specificity in UC than in Crohn’s disease. Increasing inflammation score was associated with a significant decrease in mt-sDNAHgb- test score [ = 0.028] amongst neoplasia-negative individuals, but not in patients with ACRN.

Conclusions

These data highlight the potential of multitarget stool-DNA marker testing as an important addition to colorectal cancer surveillance by complementing colonoscopic evaluations in IBD patients.
Distinct Alterations in Central Pain Processing of Visceral and Somatic Pain in Quiescent Ulcerative Colitis Compared to Irritable Bowel Syndrome and Health
Authors: Öhlmann Hanna , Lanters Laura Ricarda , Theysohn Nina , Langhorst Jost , Engler Harald , Icenhour Adriane , Elsenbruch Sigrid
Published: May 2023

Background and Aims

Despite relevance to pain chronicity, disease burden, and treatment, mechanisms of pain perception for different types of acute pain remain incompletely understood in patients with inflammatory bowel disease [IBD]. Building on experimental research across pain modalities, we herein addressed behavioural and neural correlates of visceral versus somatic pain processing in women with quiescent ulcerative colitis [UC] compared to irritable bowel syndrome [IBS] as a patient control group and healthy women [HC].

Methods

Thresholds for visceral and somatic pain were assessed with rectal distensions and cutaneous thermal pain, respectively. Using functional magnetic resonance imaging, neural and behavioural responses to individually calibrated and intensity-matched painful stimuli from both modalities were compared.

Results

Pain thresholds were comparable across groups, but visceral thresholds correlated with gastrointestinal symptom severity and chronic stress burden exclusively within UC. Upon experience of visceral and somatic pain, both control groups demonstrated enhanced visceral pain-induced neural activation and greater perceived pain intensity, whereas UC patients failed to differentiate between pain modalities at both behavioural and neural levels.

Conclusions

When confronted with acute pain from multiple bodily sites, UC patients’ responses are distinctly altered. Their failure to prioritise pain arising from the viscera may reflect a lack of adaptive behavioural flexibility, possibly resulting from long-lasting central effects of repeated intestinal inflammatory insults persisting during remission. The role of psychological factors, particularly chronic stress, in visceral sensitivity and disease-specific alterations in the response to acute pain call for dedicated mechanistic research as a basis for tailoring interventions for intestinal and extraintestinal pain symptoms in IBD.
The AppCare-HF randomized clinical trial: a feasibility study of a novel self-care support mobile app for individuals with chronic heart failure
Authors: Yokota Takashi , Fukushima Arata , Tsuchihashi-Makaya Miyuki , Abe Takahiro , Takada Shingo , Furihata Takaaki , Ishimori Naoki , Fujino Takeo , Kinugawa Shintaro , Ohta Masayuki , Kakinoki Shigeo , Yokota Isao , Endoh Akira , Yoshino Masanori , Tsutsui Hiroyuki
Published: May 2023

Aims

We evaluated a self-care intervention with a novel mobile application (app) in chronic heart failure (HF) patients. To facilitate patient-centred care in HF management, we developed a self-care support mobile app to boost HF patients’ optimal self-care.

Methods and results

We conducted a multicentre, randomized, controlled study evaluating the feasibility of the self-care support mobile app designed for use by HF patients. The app consists of a self-monitoring assistant, education, and automated alerts of possible worsening HF. The intervention group received a tablet personal computer (PC) with the self-care support app installed, and the control group received a HF diary. All patients performed self-monitoring at home for 2 months. Their self-care behaviours were evaluated by the European Heart Failure Self-Care Behaviour Scale. We enrolled 24 outpatients with chronic HF (ages 31–78 years; 6 women, 18 men) who had a history of HF hospitalization. During the 2 month study period, the intervention group (n = 13) showed excellent adherence to the self-monitoring of each vital sign, with a median [interquartile range (IQR)] ratio of self-monitoring adherence for blood pressure, body weight, and body temperature at 100% (92–100%) and for oxygen saturation at 100% (91–100%). At 2 months, the intervention group’s self-care behaviour score was significantly improved compared with the control group (n = 11) [median (IQR): 16 (16–22) vs. 28 (20–36), P = 0.02], but the HF Knowledge Scale, the General Self-Efficacy Scale, and the Short Form-8 Health Survey scores did not differ between the groups.

Conclusion

The novel mobile app for HF is feasible.
Age moderates change in disease-related stress among congenital heart disease survivors: a 6-year follow-up
Authors: Swenski Taylor N , Fox Kristen R , Udaipuria Shivika , Korth Christina X , Daniels Curt J , Jackson Jamie L
Published: May 2023

Aims

As congenital heart disease (CHD) survivors age, they are confronted with elevated risk of cardiovascular morbidity and increasingly complex disease self-management demands. Given that stress is associated with poor physical and psychosocial outcomes, it is crucial to examine how disease-related stress changes over time in this population. However, this outcome has received little research attention to date. This study aimed to identify demographic and clinical predictors of change in disease-related stress over 6 years among CHD survivors.

Methods and results

Congenital heart disease survivors (N = 252, Mage = 25.6 ± 7.1, 52.9% female) completed the first 13 items of the Responses to Stress Questionnaire, adapted for use among CHD survivors, to assess disease-related stressors at study entry (T1) and 6-year follow-up (T2). Age, gender, estimated family income, and New York Heart Association (NYHA) functional class at T1 were entered into mixed linear models to determine their impact on change in disease-related stress. Older age (P < 0.001), lower income (P < 0.001), and presence of functional limitations (NYHA ≥ II) (P < 0.001) predicted greater increases in disease-related stress. When controlling for NYHA, functional class, and income, a significant time by age interaction was identified such that disease-related stress increased over time among those who were adolescents at T1 [b = 4.20, P = 0.010, 95% confidence interval (1.01, 7.40)], but remained stable among young adults.

Conclusion

The transition from adolescence to adulthood may be a period of increasing disease-related stress. Healthcare providers should consider screening adolescents for elevated disease-related stress during transition education and provide resources to bolster resilience.
Intertextual Irony: Between Relevance Theory and Umberto Eco
Authors: Brondino Andrea
Published: May 2023

This article discusses the advantages deriving from the interaction of pragmatics and literary theory in the study of literary irony. The first section argues that the current (mis)understanding of irony is the result of a centuries-long intertwinement between rhetorical and philosophical discourses. The paper then shows how the echoic theory of irony, devised by Dan Sperber and Deirdre Wilson within the broader framework of their Relevance Theory, provides literary scholars with a different and potentially useful notion of irony and its functions. The third section compares echoic irony to Umberto Eco’s definition of irony. Intertextual irony is then defined, and identified as a fourth type of irony, in addition to verbal, situational or dramatic ironies. Literary examples and implications of intertextual irony are also analysed. In the fourth and final section expressions of a diffuse sense of rejection of irony in contemporary culture are briefly discussed. By applying an innovative methodology to the study of figurative language, this article aims to introduce the concept of intertextual irony as a reader-oriented tool for literary analysis, as well as to emphasize the role that pragmatics can play in the refinement of the vocabulary of literary criticism and theory.
Estimating the thermal conductivity of plutonic rocks from major oxide composition using machine learning
Authors: Yu Ruyang , Jiang Shu , Fuchs Sven , Peng Peng , Li Yuanping , Wang Hu
Published: May 2023

The accurate estimation of temperature distribution in the earth's crust and modelling of heat-related processes in geodynamics requires knowledge of the thermal conductivity of plutonic rocks. This study compiled an extensive data set of 530 representative plutonic rock samples, including thermal conductivity, major oxide composition and (for two subsets of data) modal mineralogy. For the first time, three machine learning algorithms (ML; i.e. support vector regression, random forest and extreme gradient boosting) were employed to estimate the thermal conductivity of plutonic rocks using the major oxide composition feature as input variables. The performance of these ML-based models was evaluated against a geochemically compositional model and eight mineral-driven physically based empirical mixing models. Results show that the means of predicted thermal conductivity by the ML-based models and the geochemically compositional model are not significantly different from the measured thermal conductivity at a significance level of 5 per cent. However, the ML-based models outperformed the best-performing non-ML model, the geochemically compositional model. The highest prediction accuracy was achieved by extreme gradient boosting, which reduced the mean absolute percentage error and root mean square error by more than 50 per cent. Furthermore, SiO2 is confirmed as the most important independent variable, followed by Al2O3, TiO2, CaO and K2O. The turning point observed in the thermal conductivity trend with SiO2 wt per cent may be primarily attributed to variations in mineral composition within the subgroup of igneous rock types classified based on SiO2 wt per cent. This study explores, for the first time, the use of ML algorithms to estimate the thermal conductivity of plutonic rocks from their major oxide composition.
Impact of Vedolizumab on Extraintestinal Manifestations in Inflammatory Bowel Disease: Results From a Descriptive, Retrospective, Real-world Study
Authors: Kopylov Uri , Burisch Johan , Ben-Horin Shomron , Braegger Fiona , Fernández-Nistal Alonso , Lara Nuria , Heinrich Henriette Sophie , Vavricka Stephan R
Published: May 2023

Background

Patients with inflammatory bowel disease (IBD), including Crohn’s disease and ulcerative colitis, may develop extraintestinal manifestations (EIMs). The EMOTIVE study aimed to analyze the effect of vedolizumab on EIMs in a real-world cohort of patients with IBD.

Methods

This multicenter, descriptive, retrospective study was conducted in Belgium, Denmark, Israel, the Netherlands, and Switzerland in adults with moderately to severely active IBD and concurrent active EIMs at vedolizumab initiation (index date), with a ≥6-month follow-up after the index date. The primary endpoint was resolution of all EIMs within 6 months of vedolizumab initiation.

Results

In 99 eligible patients, the most frequent EIMs were arthralgia (69.7%), peripheral spondyloarthritis (21.2%), and axial spondyloarthritis (10.1%). Within 6 and 12 months of vedolizumab initiation, 19.2% and 25.3% of patients reported resolution of all EIMs, while 36.5% and 49.5% of all EIMs were reported to be improved (combination of resolution and partial response), respectively. Vedolizumab treatment persistence at 12 months was 82.8%. Adverse events were reported in 18.2% of patients, with the most frequent being arthralgia (4.0%).

Conclusions

This real-world study showed resolution of all EIMs in up to one-fourth of patients with IBD and improvement in up to half of EIMs within 12 months of vedolizumab treatment. Overall, vedolizumab was effective on EIMs in patients with IBD and showed a good safety profile.
The Function of the Mammal Extrinsic Tongue Musculature in the Transition from Suckling to Drinking
Authors: Steer K E , Johnson M L , Adjerid K , Bond L E , Howe S P , Khalif A , Nkachukwu K C , Edmonds C E , German R Z , Mayerl C J
Published: May 2023

Synopsis

The transition from suckling to drinking is a developmental pathway that all mammals take. In both behaviors, the tongue is the primary structure involved in acquiring, transporting, and swallowing the liquid. However, the two processes are fundamentally different: during suckling, the tongue must function as a pump to generate suction to move milk, whereas during drinking, the tongue moves backwards and forwards through the mouth to acquire and move water. Despite these fundamental differences, we have little understanding of how tongues role varies between these behaviors. We used an infant pig model to investigate the relationships between anatomy, physiology, and function of the tongue to examine how lingual function is modulated in the transition from infancy to adulthood. We found that while some muscles were proportionally largest at birth, others were proportionally larger at the time of weaning. Furthermore, we found variation in tongue movements between suckling and drinking along both the mediolateral and anteroposterior axes, resulting in differences in tongue deformation between the two behaviors. The extrinsic tongue muscles also changed in function differently between drinking and suckling. Genioglossus increased its activity and turned on and off earlier in the cycle during drinking, whereas hyoglossus fired at lower amplitudes during drinking, and turned on and off later in the cycle. Together, the data highlight the significant need for high neuroplasticity in the control of the tongue at a young age in mammals and suggest that the ability to do so is key in the ontogeny and evolution of feeding in these animals.
Organizational team formation: projects, structures, and transactive memory
Authors: Choi Seungho , Miller Kent
Published: May 2023

Team formation brings together organizational members with complementary capabilities to address projects. This study examines how project-based organizations form teams in response to an ongoing stream of different projects. We consider team formation a phenomenon shaped by organization structure, project attributes, and learning from project experience. We address the effects of two alternative organization structures (functional and team-based) and four project attributes (project size, heterogeneity, decomposability, and ambiguity) on the efficiency of project team staffing. We build these features into two agent-based models grounded on nine case studies of project-based organizations. These models highlight how organizations achieve efficiency in team formation over time as transactive memory develops in response to ongoing project variation. Our models explain how organization structure and particular project attributes affect the development and application of transactive memory.
Results and insights after 413 TAVI procedures performed by cardiac surgeons on their own
Authors: Malvindi Pietro Giorgio , Berretta Paolo , Capestro Filippo , Bifulco Olimpia , Alfonsi Jacopo , Cefarelli Mariano , Pierri Michele Danilo , Di Eusanio Marco
Published: May 2023

OBJECTIVES

Current evidence on transcatheter aortic valve implantation (TAVI) has been generated exclusively by cardiology studies and no operative data from cardiac surgeons are available. Here, we describe the development of our TAVI programme and report the results of transfemoral (TF) TAVI done by cardiac surgeons on their own.

METHODS

This study included all the TAVI procedures on native valve performed at Cardiac Surgery Unit, Ospedali Riuniti di Ancona, during the period October 2018 to July 2022. Relevant prospectively collected preoperative, intraprocedural and postoperative data were retrieved from the Institutional database.

RESULTS

A total of 413 patients were included in the study. Mean patients’ age was 82 years and among them 44% (180/413) were male. STS score was 3.1% (2.2–4.4). Eighty patients underwent transapical TAVI and 333 patients had a TF approach. We progressively moved from transapical TAVI towards TF procedures that are now routinely performed on conscious sedation and using a fully percutaneous approach. After TF TAVI, 30-day mortality rate was 1%, cerebral stroke occurred in 2% of the cases, permanent pacemaker implantation was necessary in 23% of the patients and in 6% of the cases there was a moderate/severe degree of aortic regurgitation. There was no association between operators performing TAVI and 30-day mortality.

CONCLUSIONS

The acquisition of catheter-based skills and an adequate training allowed cardiac surgeons to perform on their own awake and fully percutaneous TF TAVI with similar results when compared with major randomized clinical trials and registries’ experiences.
The net-zero and sustainability potential of SCC development, production and flowability in concrete structures
Authors: Onyelowe Kennedy C , Kontoni Denise-Penelope N
Published: May 2023

Climate action around the world has shifted to the potential of global warming contribution from the design and construction of infrastructures, especially those in demand for concrete. Concrete production and use have been identified as contributing to >5% of the world’s greenhouse gas (GHG) emissions. The main aim of this research work is to critically study the net-zero and sustainability potentials that the world can leverage on from the development, production and flowability of self-compacting concrete (SCC). Conventional concrete is made of >50% of ordinary cement, which contributes to >7% of the world’s GHG emissions. But in 1988, a fluidized concrete that compacts under its self-weight, known as SCC, was formed and developed to overcome the need for durability, skill and manpower that were dwindling in Japan at the time. This concrete created a pathway for cement to be replaced partially or totally by certain pozzolanic materials that function as viscosity-modifying admixture, high-water reducing agent or microencapsulated phase-change materials in the concrete mix. However, research findings have shown that for these materials to alter the flowability of SCC, there has to be reduced yield stress and moderate viscosity for allowable internal friction based on the Bingham model, and this has to be achieved under the same water–cement ratio. Fortunately, the implication of the use of these admixtures as replacements for cement is that there is a reduced demand for cement production and use in cleaner concrete production and, as such, a reduced CO2 emission associated with this process.
Who Feels They Can Understand and Have an Impact on Political Processes? Socio-demographic Correlates of Political Efficacy in 46 Countries, 1996–2016
Authors: Oser Jennifer , Feitosa Fernando , Dassonneville Ruth
Published: May 2023

While recent research has produced robust objective evidence of unequal representation in democracies, there is little evidence about whether this inequality is consistent with individuals’ subjective perceptions of their own political efficacy. To answer this question, we use all available data on political efficacy from the International Social Survey Programme modules for 46 countries (1996–2016) to investigate trends and correlates of external and internal political efficacy. We focus on socio-demographic characteristics that are central to recent literature on unequal representation: gender, education, and income. Our individual-level findings show that education and income are positively associated with both external and internal efficacy while being female is associated with lower levels of internal efficacy but unrelated to external efficacy. We complement these individual-level analyses with a contextual investigation of how descriptive representation contributes to efficacy gaps. Focusing on gender, we show that women feel that they have more of a say in governmental decisions in contexts with a higher level of female representation among elected representatives. We conclude by noting how future research can leverage cross-national data to identify contextual mechanisms that may have an impact upon persistent social gaps in political efficacy across contexts and over time.