bluuebunny/crossref_metadata_2025 huggingface dataset:
Determining epitope specificity of T-cell receptors with transformers
Authors: Khan Abdul Rehman , Reinders Marcel J T , Khatri Indu
Published: October 2023

T-cell receptors (TCRs) on T cells recognize and bind to epitopes presented by the major histocompatibility complex in case of an infection or cancer. However, the high diversity of TCRs, as well as their unique and complex binding mechanisms underlying epitope recognition, make it difficult to predict the binding between TCRs and epitopes. Here, we present the utility of transformers, a deep learning strategy that incorporates an attention mechanism that learns the informative features, and show that these models pre-trained on a large set of protein sequences outperform current strategies. We compared three pre-trained auto-encoder transformer models (ProtBERT, ProtAlbert, and ProtElectra) and one pre-trained auto-regressive transformer model (ProtXLNet) to predict the binding specificity of TCRs to 25 epitopes from the VDJdb database (human and murine). Two additional modifications were performed to incorporate gene usage of the TCRs in the four transformer models. Of all 12 transformer implementations (four models with three different modifications), a modified version of the ProtXLNet model could predict TCR–epitope pairs with the highest accuracy (weighted F1 score 0.55 simultaneously considering all 25 epitopes). The modification included additional features representing the gene names for the TCRs. We also showed that the basic implementation of transformers outperformed the previously available methods, i.e. TCRGP, TCRdist, and DeepTCR, developed for the same biological problem, especially for the hard-to-classify labels. We show that the proficiency of transformers in attention learning can be made operational in a complex biological setting like TCR binding prediction. Further ingenuity in utilizing the full potential of transformers, either through attention head visualization or introducing additional features, can extend T-cell research avenues.

Availability and implementation

Data and code are available on https://github.com/InduKhatri/tcrformer.
MosaiCatcher v2: a single-cell structural variations detection and analysis reference framework based on Strand-seq
Authors: Weber Thomas , Cosenza Marco Raffaele , Korbel Jan
Published: October 2023

Single-cell DNA template strand sequencing (Strand-seq) allows a range of various genomic analysis including chromosome length haplotype phasing and structural variation (SV) calling in individual cells. Here, we present MosaiCatcher v2, a standardized workflow and reference framework for single-cell SV detection using Strand-seq. This framework introduces a range of functionalities, including: an automated upstream Quality Control (QC) and assembly sub-workflow that relies on multiple genome assemblies and incorporates a multistep normalization module, integration of the single-cell nucleosome occupancy and genetic variation analysis SV functional characterization and of the ArbiGent SV genotyping modules, platform portability, as well as a user-friendly and shareable web report. These new features of MosaiCatcher v2 enable reproducible computational processing of Strand-seq data, which are increasingly used in human genetics and single-cell genomics, toward production environments. MosaiCatcher v2 is compatible with both container and conda environments, ensuring reproducibility and robustness and positioning the framework as a cornerstone in computational processing of Strand-seq data.

Availability and implementation

MosaiCatcher v2 is a standardized workflow, implemented using the Snakemake workflow management system. The pipeline is available on GitHub: https://github.com/friendsofstrandseq/mosaicatcher-pipeline/ and on the snakemake-workflow-catalog: https://snakemake.github.io/snakemake-workflow-catalog/?usage=friendsofstrandseq/mosaicatcher-pipeline. Strand-seq example input data used in the publication can be found in the Data availability statement. Additionally, a lightweight dataset for test purposes can be found on the GitHub repository.
Automated calibration of consensus weighted distance-based clustering approaches using sharp
Authors: Bodinier Barbara , Vuckovic Dragana , Rodrigues Sabrina , Filippi Sarah , Chiquet Julien , Chadeau-Hyam Marc
Published: October 2023

Motivation

In consensus clustering, a clustering algorithm is used in combination with a subsampling procedure to detect stable clusters. Previous studies on both simulated and real data suggest that consensus clustering outperforms native algorithms.

Results

We extend here consensus clustering to allow for attribute weighting in the calculation of pairwise distances using existing regularized approaches. We propose a procedure for the calibration of the number of clusters (and regularization parameter) by maximizing the sharp score, a novel stability score calculated directly from consensus clustering outputs, making it extremely computationally competitive. Our simulation study shows better clustering performances of (i) approaches calibrated by maximizing the sharp score compared to existing calibration scores and (ii) weighted compared to unweighted approaches in the presence of features that do not contribute to cluster definition. Application on real gene expression data measured in lung tissue reveals clear clusters corresponding to different lung cancer subtypes.

Availability and implementation

The R package sharp (version ≥1.4.3) is available on CRAN at https://CRAN.R-project.org/package=sharp.
EVRC: reconstruction of chromosome 3D structure models using error-vector resultant algorithm with clustering coefficient
Authors: Wang Xiao , Gu Wei-Cheng , Li Jie , Ma Bin-Guang
Published: October 2023

Motivation

Reconstruction of 3D structure models is of great importance for the study of chromosome function. Software tools for this task are highly needed.

Results

We present a novel reconstruction algorithm, called EVRC, which utilizes co-clustering coefficients and error-vector resultant for chromosome 3D structure reconstruction. As an update of our previous EVR algorithm, EVRC now can deal with both single and multiple chromosomes in structure modeling. To evaluate the effectiveness and accuracy of the EVRC algorithm, we applied it to simulation datasets and real Hi-C datasets. The results show that the reconstructed structures have high similarity to the original/real structures, indicating the effectiveness and robustness of the EVRC algorithm. Furthermore, we applied the algorithm to the 3D conformation reconstruction of the wild-type and mutant Arabidopsis thaliana chromosomes and demonstrated the differences in structural characteristics between different chromosomes. We also accurately showed the conformational change in the centromere region of the mutant compared with the wild-type of Arabidopsis chromosome 1. Our EVRC algorithm is a valuable software tool for the field of chromatin structure reconstruction, and holds great promise for advancing our understanding on the chromosome functions.

Availability and implementation

The software is available at https://github.com/mbglab/EVRC.
Luteinizing hormone stimulates ingression of mural granulosa cells within the mouse preovulatory follicle
Authors: Owen Corie M , Jaffe Laurinda A
Published: October 2023

Luteinizing hormone (LH) induces ovulation by acting on its receptors in the mural granulosa cells that surround a mammalian oocyte in an ovarian follicle. However, much remains unknown about how activation of the LH receptor modifies the structure of the follicle such that the oocyte is released and the follicle remnants are transformed into the corpus luteum. The present study shows that the preovulatory surge of LH stimulates LH receptor-expressing granulosa cells, initially located almost entirely in the outer layers of the mural granulosa, to rapidly extend inwards, intercalating between other cells. The cellular ingression begins within 30 min of the peak of the LH surge, and the proportion of LH receptor-expressing cell bodies in the inner half of the mural granulosa layer increases until the time of ovulation, which occurs at about 10 h after the LH peak. During this time, many of the initially flask-shaped cells appear to detach from the basal lamina, acquiring a rounder shape with multiple filipodia. Starting at about 4 h after the LH peak, the mural granulosa layer at the apical surface of the follicle where ovulation will occur begins to thin, and the basolateral surface develops invaginations and constrictions. Our findings raise the question of whether LH stimulation of granulosa cell ingression may contribute to these changes in the follicular structure that enable ovulation.
Robustness of quantifying mediating effects of genetically regulated expression on complex traits with mediated expression score regression
Authors: Lin Chen , Liu Wei , Jiang Wei , Zhao Hongyu
Published: October 2023

Genetic association signals have been mostly found in noncoding regions through genome-wide association studies (GWAS), suggesting the roles of gene expression regulation in human diseases and traits. However, there has been limited success in colocalizing expression quantitative trait locus (eQTL) with disease-associated variants. Mediated expression score regression (MESC) is a recently proposed method to quantify the proportion of trait heritability mediated by genetically regulated gene expressions (GReX). Applications of MESC to GWAS results have yielded low estimation of mediated heritability for many traits. As MESC relies on stringent independence assumptions between cis-eQTL effects, gene effects, and nonmediated SNP effects, it may fail to characterize the true relationships between those effect sizes, which leads to biased results. Here, we consider the robustness of MESC to investigate whether the low fraction of mediated heritability inferred by MESC reflects biological reality for complex traits or is an underestimation caused by model misspecifications. Our results suggest that MESC may lead to biased estimates of mediated heritability with misspecification of gene annotations leading to underestimation, whereas misspecification of SNP annotations may lead to overestimation. Furthermore, errors in eQTL effect estimates may lead to underestimation of mediated heritability.
Janus kinase inhibitor for anti-transcription intermediary factor 1-γ positive cancer-associated dermatomyositis
Authors: Wu Wanlong , Chen Jinju , Zhu Linling , Sha Yaping , Wang Kaiwen , Zhao Jiangfeng , Ye Chunhua , Ye Shuang
Published: October 2023

In this retrospective case series, off-label use of Janus kinase inhibitor rapidly and significantly ameliorated the active cutaneous disease in all five glucocorticoid-resistant patients with cancer-associated dermatomyositis who had anti-transcription intermediary factor 1-γ antibodies, showing a promising steroid-sparing effect and a generally well-tolerated safety profile beyond 1-year follow-up.
Subcortical contributions to the sense of body ownership
Authors: Crucianelli Laura , Reader Arran T , Ehrsson H Henrik
Published: October 2023

The sense of body ownership (i.e. the feeling that our body or its parts belong to us) plays a key role in bodily self-consciousness and is believed to stem from multisensory integration. Experimental paradigms such as the rubber hand illusion have been developed to allow the controlled manipulation of body ownership in laboratory settings, providing effective tools for investigating malleability in the sense of body ownership and the boundaries that distinguish self from other.

Neuroimaging studies of body ownership converge on the involvement of several cortical regions, including the premotor cortex and posterior parietal cortex. However, relatively less attention has been paid to subcortical structures that may also contribute to body ownership perception, such as the cerebellum and putamen. Here, on the basis of neuroimaging and neuropsychological observations, we provide an overview of relevant subcortical regions and consider their potential role in generating and maintaining a sense of ownership over the body. We also suggest novel avenues for future research targeting the role of subcortical regions in making sense of the body as our own.
Rapid response of erythrodermic pityriasis rubra pilaris to tildrakizumab
Authors: Villa-Gonzalez Jose Maria , Gonzalez-Hermosa Maria Rosario , Atxutegi-Ayesta Xabier , Ratón Nieto Juan Antonio , Gardeazabal García Jesús , Lasa Elgezua Olatz
Published: October 2023

The cases of two patients with erythrodermic pityriasis rubra pilaris that showed a rapid and virtually complete response to tildrakizumab are presented. Treatment of pityriasis rubra pilaris remains challenging and there is very little evidence about use of interleukin-23 blockers in this condition. These cases may contribute to extending the available therapeutic options, especially when a fast clearance of the lesions is needed.
Tubulo-interstitial inflammation increases the risk of graft loss after the recurrence of IgA nephropathy
Authors: Rodrigo Emilio , Quintana Luis F , Vázquez-Sánchez Teresa , Sánchez-Fructuoso Ana , Buxeda Anna , Gavela Eva , Cazorla Juan M , Cabello Sheila , Beneyto Isabel , López-Oliva María O , Diekmann Fritz , Gómez-Ortega José M , Calvo Romero Natividad , Pérez-Sáez María J , Sancho Asunción , Mazuecos Auxiliadora , Espí-Reig Jordi , Jiménez Carlos , Hernández Domingo
Published: October 2023

Background

Immunoglobulin A nephropathy (IgAN) is the most frequent recurrent disease in kidney transplant recipients and its recurrence contributes to reducing graft survival. Several variables at the time of recurrence have been associated with a higher risk of graft loss. The presence of clinical or subclinical inflammation has been associated with a higher risk of kidney graft loss, but it is not precisely known how it influences the outcome of patients with recurrent IgAN.

Methods

We performed a multicentre retrospective study including kidney transplant recipients with biopsy-proven recurrence of IgAN in which Banff and Oxford classification scores were available. ‘Tubulo-interstitial inflammation’ (TII) was defined when ‘t’ or ‘i’ were ≥2. The main endpoint was progression to chronic kidney disease (CKD) stage 5 or to death censored-graft loss (CKD5/DCGL).

Results

A total of 119 kidney transplant recipients with IgAN recurrence were included and 23 of them showed TII. Median follow-up was 102.9 months and 39 (32.8%) patients reached CKD5/DCGL. TII related to a higher risk of CKD5/DCGL (3 years 18.0% vs 45.3%, log-rank 7.588, P = .006). After multivariate analysis, TII remained related to the risk of CKD5/DCGL (HR 2.344, 95% CI 1.119–4.910, P = .024) independently of other histologic and clinical variables.

Conclusions

In kidney transplant recipients with IgAN recurrence, TII contributes to increasing the risk of CKD5/DCGL independently of previously well-known variables. We suggest adding TII along with the Oxford classification to the clinical variables to identify recurrent IgAN patients at increased risk of graft loss who might benefit from intensified immunosuppression or specific IgAN therapies.
Brugada phenocopy with altered ST-segment elevation in pericardial diffuse large B-cell lymphoma and effusive–constrictive pericarditis: a case report
Authors: Ishibashi Yohei , Zhang Shanshan , Tamura Shuntaro , Ishii Hideki
Published: October 2023

Background

Cardiac lymphoma is a rare disease. Effusive–constrictive pericarditis can be a characteristic of pericardial involvement in patients with this disease. Conversely, a phenotype with electrocardiogram changes similar to those of Brugada syndrome is called Brugada phenocopy, and these changes improve after treatment.

Case summary

A 71-year-old man was transported to our hospital with chest pain, hypotension, and ST-segment elevation in V1 and V2 leads during maintenance dialysis for renal failure. After arrival at the hospital, his ST-segment elevation disappeared, and emergency coronary angiography scan revealed no significant coronary artery stenoses or obstructions. His computed tomography and echocardiography scans revealed pericardial effusion and an intrapericardial mass. Further, his blood pressure dropped and ST-segment elevation recurred during dialysis after 7 days. Thus, pericardiocentesis was performed, but haemodynamic improvement was insufficient, and right catheterization findings suggested effusive–constrictive pericarditis. Meanwhile, flow cytometry of the pericardial fluid suggested the diagnosis of B-cell lymphoma; however, radical chemoradiotherapy was impossible because of cardiogenic shock. The patient died on Day 17. Further, autopsy revealed diffuse large B-cell lymphoma with pericardial and myocardial infiltration.

Discussion

Cardiac lymphoma is rare but can be associated with effusive–constrictive pericarditis, which may be difficult to manage even with pericardial drainage. In such cases, radical treatment, including chemotherapy, should be promptly considered, if possible. Our patient presented with Brugada-type electrocardiogram but no syncope or family history, suggesting Brugada phenocopy and not true Brugada syndrome due to cardiac lymphoma. Notably, temporary improvement in ST-segment elevation was observed despite the absence of treatment.
Improving cardiovascular risk prediction through machine learning modelling of irregularly repeated electronic health records
Authors: Li Chaiquan , Liu Xiaofei , Shen Peng , Sun Yexiang , Zhou Tianjing , Chen Weiye , Chen Qi , Lin Hongbo , Tang Xun , Gao Pei
Published: October 2023

Aims

Existing electronic health records (EHRs) often consist of abundant but irregular longitudinal measurements of risk factors. In this study, we aim to leverage such data to improve the risk prediction of atherosclerotic cardiovascular disease (ASCVD) by applying machine learning (ML) algorithms, which can allow automatic screening of the population.

Methods and results

A total of 215 744 Chinese adults aged between 40 and 79 without a history of cardiovascular disease were included (6081 cases) from an EHR-based longitudinal cohort study. To allow interpretability of the model, the predictors of demographic characteristics, medication treatment, and repeatedly measured records of lipids, glycaemia, obesity, blood pressure, and renal function were used. The primary outcome was ASCVD, defined as non-fatal acute myocardial infarction, coronary heart disease death, or fatal and non-fatal stroke. The eXtreme Gradient boosting (XGBoost) algorithm and Least Absolute Shrinkage and Selection Operator (LASSO) regression models were derived to predict the 5-year ASCVD risk. In the validation set, compared with the refitted Chinese guideline–recommended Cox model (i.e. the China-PAR), the XGBoost model had a significantly higher C-statistic of 0.792, (the differences in the C-statistics: 0.011, 0.006–0.017, P < 0.001), with similar results reported for LASSO regression (the differences in the C-statistics: 0.008, 0.005–0.011, P < 0.001). The XGBoost model demonstrated the best calibration performance (men: Dx = 0.598, P = 0.75; women: Dx = 1.867, P = 0.08). Moreover, the risk distribution of the ML algorithms differed from that of the conventional model. The net reclassification improvement rates of XGBoost and LASSO over the Cox model were 3.9% (1.4–6.4%) and 2.8% (0.7–4.9%), respectively.

Conclusion

Machine learning algorithms with irregular, repeated real-world data could improve cardiovascular risk prediction. They demonstrated significantly better performance for reclassification to identify the high-risk population correctly.
Safety and care of no fasting prior to catheterization laboratory procedures: a non-inferiority randomized control trial protocol (SCOFF trial)
Authors: Ferreira David , Hardy Jack , Meere Will , Butel-Simoes Lloyd , McGee Michael , Whitehead Nicholas , Healey Paul , Ford Tom , Oldmeadow Christopher , Attia John , Wilsmore Bradley , Collins Nicholas , Boyle Andrew
Published: October 2023

Aims

Cardiac catheterization procedures are typically performed with local anaesthetic and proceduralist guided sedation. Various fasting regimens are routinely implemented prior to these procedures, noting the absence of prospective evidence, aiming to reduce aspiration risk. However, there are additional risks from fasting including patient discomfort, intravascular volume depletion, stimulus for neuro-cardiogenic syncope, glycaemic outcomes, and unnecessary fasting for delayed/cancelled procedures.

Methods and results

This is an investigator-initiated, multicentre, randomized trial with a prospective, open-label, blinded endpoint (PROBE) assessment based in New South Wales, Australia. Patients will be randomized 1:1 to fasting (6 h solid food and 2 h clear liquids) or to no fasting requirements. The primary outcome will be a composite of hypotension, hyperglycaemia, hypoglycaemia, and aspiration pneumonia. Secondary outcomes will include patient satisfaction, contrast-induced nephropathy, new intensive care admission, new non-invasive or invasive ventilation requirement post procedure, and 30-day mortality and readmission.

Conclusions

This is a pragmatic and clinically relevant randomised trial designed to compare fasting verse no fasting prior to cardiac catheterisation procedures. Routine fasting may not reduce peri-procedural adverse events in this setting.
The cardiovascular disease burden attributable to low physical activity in the Western Pacific Region, 1990–2019: an age–period–cohort analysis of the Global Burden of Disease study
Authors: Liu Zeye , Li Ziping , Xie Jing , Xia Ruibing , Li Yakun , Zhang Fengwen , Ouyang Wenbin , Wang Shouzheng , Pan Xiangbin
Published: October 2023

Aims

To increase the comprehensive understanding of trends in the burden of cardiovascular disease (CVD) attributable to low physical activity in the Western Pacific Region.

Methods and results

Based on data from the Global Burden of Disease study for the years 1990–2019, an age–period–cohort analysis was conducted to investigate trends in CVD-related mortality attributable to low physical activity in the Western Pacific Region and associations with age, period, and birth cohort. We also used joinpoint regression analysis to identify the periods with the most substantial changes. The results show that, the Western Pacific Region witnessed a substantial increase in CVD deaths attributable to low physical activity, accompanied by a rise in all-age CVD-related mortality. However, the age-standardized death rate was lower in the region than the global level, highlighting the importance of considering the age composition of CVD burden in the region. Countries with higher socio-demographic index (SDI) levels exhibited lower mortality than those with lower SDI levels. The longitudinal analysis using the age–period–cohort model indicated an overall improvement in CVD-related mortality attributable to low physical activity in the region, but with differences between sexes and CVD subtypes. Specific period in which CVD-related mortality decreased significantly was 2011–16, for the average annual percentage change for the period was −0.69%.

Conclusion

The study highlights the significance of addressing low physical activity as a modifiable risk factor for CVD burden in the Western Pacific Region. Further research is essential to understand the factors contributing to inter-country variations, sex disparities, and CVD subtypes distinctions.
Metabolic reconstruction of the human pathogen Candida auris: using a cross-species approach for drug target prediction
Authors: Viana Romeu , Carreiro Tiago , Couceiro Diogo , Dias Oscar , Rocha Isabel , Teixeira Miguel Cacho
Published: October 2023

Candida auris is an emerging human pathogen, associated with antifungal drug resistance and hospital candidiasis outbreaks. In this work, we present iRV973, the first reconstructed Genome-scale metabolic model (GSMM) for C. auris. The model was manually curated and experimentally validated, being able to accurately predict the specific growth rate of C. auris and the utilization of several sole carbon and nitrogen sources. The model was compared to GSMMs available for other pathogenic Candida species and exploited as a platform for cross-species comparison, aiming the analysis of their metabolic features and the identification of potential new antifungal targets common to the most prevalent pathogenic Candida species. From a metabolic point of view, we were able to identify unique enzymes in C. auris in comparison with other Candida species, which may represent unique metabolic features. Additionally, 50 enzymes were identified as potential drug targets, given their essentiality in conditions mimicking human serum, common to all four different Candida models analysed. These enzymes represent interesting drug targets for antifungal therapy, including some known targets of antifungal agents used in clinical practice, but also new potential drug targets without any human homolog or drug association in Candida species.
Genomics of the relict species Baronia brevicornis sheds light on its demographic history and genome size evolution across swallowtail butterflies
Authors: Marino Alba , Reboud Eliette L , Chevalier Emmanuelle , Tilak Marie-Ka , Contreras-Garduño Jorge , Nabholz Benoit , Condamine Fabien L
Published: October 2023

Relict species, like coelacanth, gingko, tuatara, are the remnants of formerly more ecologically and taxonomically diverse lineages. It raises the questions of why they are currently species-poor, have restrained ecology, and are often vulnerable to extinction. Estimating heterozygosity level and demographic history can guide our understanding of the evolutionary history and conservation status of relict species. However, few studies have focused on relict invertebrates compared to vertebrates. We sequenced the genome of Baronia brevicornis (Lepidoptera: Papilionidae), which is an endangered species, the sister species of all swallowtail butterflies, and is the oldest lineage of all extant butterflies. From a dried specimen, we were able to generate both long-read and short-read data and assembled a genome of 406 Mb for Baronia. We found a fairly high level of heterozygosity (0.58%) compared to other swallowtail butterflies, which contrasts with its endangered and relict status. Taking into account the high ratio of recombination over mutation, demographic analyses indicated a sharp decline of the effective population size initiated in the last million years. Moreover, the Baronia genome was used to study genome size variation in Papilionidae. Genome sizes are mostly explained by transposable elements activities, suggesting that large genomes appear to be a derived feature in swallowtail butterflies as transposable elements activity is recent and involves different transposable elements classes among species. This first Baronia genome provides a resource for assisting conservation in a flagship and relict insect species as well as for understanding swallowtail genome evolution.
Longitudinal Changes of Cognition and Frailty With All-Cause and Cause-Specific Mortality in Chinese Older Adults: An 11-Year Cohort Study
Authors: Chen Chen , Li Xinwei , Wang Jun , Zhou Jinhui , Wei Yuan , Luo Yufei , Xu Lanjing , Liu Zuyun , Lv Yuebin , Shi Xiaoming
Published: October 2023

Background and Objectives

Physical function deterioration is always accompanied by a cognitive decline in older adults. However, evidence is lacking for the long-term simultaneous changing patterns of cognition and physical frailty and their associations with mortality among older adults.

Research Design and Methods

This study included 8,231 adults aged ≥65 with a baseline and at least one follow-up assessment of both cognition and physical frailty from the 2007–2018 Chinese Longitudinal Healthy Longevity Survey. Physical frailty (FRAIL phenotype) and cognition (Mini-Mental State Examination) were applied. Group-based joint trajectory modeling was used to fit the joint trajectories of cognition and physical frailty. Cox proportional hazards model was used to evaluate the trajectory-mortality associations.

Results

Three distinct joint trajectories were identified: no joint progression (34.4%), moderate joint progression (47.0%), and rapid joint progression (18.6%). During a median follow-up of 8.3 years, the rapid joint progression group, compared to the no joint progression, had the highest risk for all-cause mortality (hazard ratio (HR), 3.37 [95% CI: 2.99–3.81]), cardiovascular (CVD) mortality (3.21 [2.08–4.96]) and non-CVD mortality (2.99 [2.28–3.92]), respectively. Joint trajectory was found to be more predictive of mortality as compared to baseline measures of cognition and/or frailty (C-statistic ranged from 0.774 to 0.798). Higher changing rates of cognition and frailty were observed among all-cause decedents compared to CVD and non-CVD decedents over a 45-year span (aged 65–110) before death.

Discussion and Implications

Our study suggested that subjects with the worst cognitive decline and severest physical frailty progression were at the highest risk for all-cause and cause-specific mortality. Our findings expand the limited prior knowledge on the dynamic course of cognition and frailty.
Active deformation in the Makran region using geological, geodetic and stress direction data sets
Authors: Ghadimi Homa , Khodaverdian Alireza , Zafarani Hamid
Published: October 2023

Neotectonic flow of the Makran subduction zone is estimated using a kinematic modelling technique based on iterated weighted least-squares that fits to all kinematic data from both geological and geophysical sources. The kinematic data set includes 87 geodetic velocities, 1962 principal stress directions, 90 fault traces, 56 geological heave rates and velocity boundary conditions. Low seismicity of western Makran compared to its eastern part, may indicate that either the subduction interface is currently locked, accumulating elastic strain or aseismic slip (creep) occurs along this part of the plate boundary. Therefore, we define two different models to evaluate the possibility of creep in the western Makran. Models define a locked subduction zone versus a steady creeping subduction for the western Makran. The locking depth of the subducting fault is also investigated, and a locking between 14 and 40–45 km depth provided the best consistency with geodetic observations. The 2 kinematic models provide long-term fault slip rates. The models estimated the shortening rate of 16.6–22.5 mm yr−1 and the strike-slip movement of 0.2–6.0 mm yr−1 for six segments along the subduction fault. The steady creeping subduction model predicts a 1–2 mm yr−1 lower shortening rate than the locked model for the Makran subduction fault (MSF). To verify the results, the estimated fault slip rates are compared to slip rates based on the geodetical and geological studies, which have not been used as model inputs. Our estimated rates fall within the range of geodetic rates and are even more consistent with geological rates than previous GPS-based estimates. In addition, the model provides the long-term velocity, and distributed permanent strain rates in the region. Based on the SHIFT hypotheses, long-term seismicity rates are computed for both models based on the estimated strain rate. These maps were compared with seismic catalogues. The estimated seismicity rate for the western part of Makran from the creeping subduction model is more compatible with the observation. The results of two deformation models lead us to a coupling ratio of ∼0.1 for the western MSF.
Tn antigen interactions of macrophage galactose-type lectin (MGL) in immune function and disease
Authors: Tumoglu Berna , Keelaghan Aidan , Avci Fikri Y
Published: October 2023

Protein-carbohydrate interactions are essential in maintaining immune homeostasis and orchestrating inflammatory and regulatory immune processes. This review elucidates the immune interactions of macrophage galactose-type lectin (MGL, CD301) and Tn carbohydrate antigen. MGL is a C-type lectin receptor (CLR) primarily expressed by myeloid cells such as macrophages and immature dendritic cells. MGL recognizes terminal O-linked N-acetylgalactosamine (GalNAc) residue on the surface proteins, also known as Tn antigen (Tn). Tn is a truncated form of the elongated cell surface O-glycan. The hypoglycosylation leading to Tn may occur when the enzyme responsible for O-glycan elongation—T-synthase—or its associated chaperone—Cosmc—becomes functionally inhibited. As reviewed here, Tn expression is observed in many different neoplastic and non-neoplastic diseases, and the recognition of Tn by MGL plays an important role in regulating effector T cells, immune suppression, and the recognition of pathogens.
Growing administrative complexity in the 340B program and the rise of third-party administrators
Authors: Nikpay Sayeh , Halvorson Lucas
Published: October 2023

The 1992 340B drug discount program lowers drug costs and provides a source of revenue for safety-net providers by entitling them to discounts on drugs for all patients, including those with insurance. As 340B has grown so has the administrative complexity of the program, creating a market for third-party administrators (TPAs) to manage both formal and informal requirements in exchange for fees. Although TPAs are playing an important role in the 340B ecosystem, the TPA market is poorly understood, along several dimensions including its size, specialization, competitiveness, and scope of services offered. In this brief report, we report the results of original market research on TPA firms to address unanswered questions and identify gaps in knowledge. We identify 48 TPA firms, including 8 owned by private equity firms, 2 owned by software companies, and 6 owned by a variety of vertically integrated health care stakeholders such as pharmacies, pharmaceutical benefit managers, and pharmaceutical wholesalers. We identified 7 services offered by TPAs including patient discount cards (13), enrollment (31), auditing (45), revenue capture (42), referral management (9), inventory management (19), and 340B ESP assistance (9). Our results suggest that TPAs are involved in many diverse functions related to 340B.
Corporate governance, sustainability and ethics
Authors: Crowe Jonathan , Bradshaw Tony
Published: October 2023

This chapter considers the issues that the provision of high-quality financial information encompasses. It explains what corporate governance is, its significance, and the reporting requirements. In addition, the chapter also explores the five key areas of corporate governance included in the Financial Reporting Council's (FRC) UK Corporate Governance Code 2014. The chapter also looks at the increasing significance of corporate sustainability issues for companies and their stakeholders. Then, it presents how corporate sustainability issues may be reported. Lastly, it delves into how ethical behaviour is integral to the financial reporting chain.
Published financial statements of companies
Authors: jennifer maynard
Published: October 2023

This chapter examines the requirements of the standards for the presentation of the statements of financial position, comprehensive income, and changes in equity, including alternative presentations. IAS 1 Presentation of Financial Statements sets out the overall requirements for the presentation of the statements of financial position, comprehensive income and changes in equity, guidelines for their structure, and requirements for their content. IAS 7 Statement of Cash Flows sets out the same requirements for the statement of cash flows. IAS 8 Accounting Policies, Changes in Accounting Estimates and Errors specifies further details of how companies should select and disclose the accounting policies that underpin their financial numbers. Most importantly, the chapter illustrates how the financial statements are drawn up and presented through the use of examples and company annual reports.
Techniques for the interpretation of financial statements
Authors: Maynard Jennifer
Published: October 2023

This chapter provides details on a range of standard analytical techniques that can be applied in financial statement interpretation. These techniques are used to explain the implication of accounting methods specified by financial reporting standards for users' interpretation of the financial information provided. The chapter introduces the horizontal, vertical, and ratio analytical techniques. Moreover, it considers the calculations and interpretations of the main ratios in order to analyze profitability, liquidity, efficiency, gearing, and investor returns. Lastly, it tackles how the statement of cash flow is interpreted and the limitations of ratio analysis.
Intangible assets
Authors: jennifer maynard
Published: October 2023

This chapter looks into the accounting methods for intangible assets, an identifiable non-monetary asset without physical substance. It begins with a discussion of the importance of intangible assets and the issues in their accounting and valuation. Then, it explores how intangible assets are accounted for in accordance with International Accounting Standard (IAS) 38 Intangible Assets at the point of recognition. In addition to the definition of intangible assets, the chapter also provides the principles on how to distinguish between those purchased externally, acquired as part of a business combination, and internally generated. The latter part of the chapter delves into the financial reporting and disclosure of intangible assets and how they affect the users of the statements of financial position.
Interpretation of financial statements revisited
Authors: jennifer maynard
Published: October 2023

This chapter revisits the techniques for the interpretation of financial statements, which were introduced in Chapter 5. It uses the basic analytical tools discussed in the chapter together with details of what constitutes published financial statements, and knowledge of the accounting methods used in the recognition and measurement of many of the key figures in financial statements. It then introduces the CORE approach (context, overview, ratios, and evaluation), a model for interpretation which uses all information in financial statements. The indicators for financial distress are discussed. Issues on the effect of recognition and measurement methods and changes in accounting policies are also explored.
Introducing Business Ethics
Authors: Crane Andrew , Matten Dirk , Glozer Sarah , Spence Laura J.
Published: October 2023

This chapter presents a basic introduction to the concept of business ethics and its importance both at an academic level and in terms of practical management in different types of organizations. It starts by describing the relationship between business ethics and the law, then distinguishes between ethics, morality, and ethical theory. The chapter then introduces two of the main themes of the book: globalization and sustainability. It argues that business ethics has been recontextualized by the forces of globalization, necessitating a distinctly global view of ethical problems and practices in business. Ultimately, the chapter explains how the ‘triple bottom line’ of sustainability is a key goal for business ethics. It also elaborates on different international perspectives on business ethics, including European, Asian, and North American perspectives.
Suppliers, Competitors, and Business Ethics
Authors: Crane Andrew , Matten Dirk , Glozer Sarah , Spence Laura J.
Published: October 2023

This chapter highlights the ethical issues arising in relation to firms' suppliers and competitors. It looks at the problems such as conflict of interest, bribery, and unfair competition, and moves on to discuss the global supply-chain and ethical sourcing. The chapter also narrates the ethical challenges of global business networks, including from the perspective of small firms. It then demonstrates the role of corporations in influencing the social and environmental choices of suppliers and competitors through their business relationships. The chapter concludes by exploring the challenges of sustainable supply-chain management and industrial ecosystems. It also points out the implications for sustainability of relationships with suppliers and competitors.
Civil Society and Business Ethics
Authors: Crane Andrew , Matten Dirk , Glozer Sarah , Spence Laura J.
Published: October 2023

This chapter shows the relationships between businesses and civil society organizations (CSOs), addressing the changing patterns of relationships between these traditionally adversarial institutions. It looks at the role played by various types of CSOs as stakeholders of corporations, both directly and indirectly. The chapter also explores the ethics of pressure group tactics, business–CSO collaboration, and social enterprise. The chapter then jumps to review the impacts of globalization on the nature and extent of the role played by civil society towards corporations. It further examines the different relationships between business and civil society and their impact on corporate responsibility. Ultimately, the chapter discusses the role of civil society in enhancing corporate sustainability.
Accounting for Depreciation and Bad Debts
Authors: Carey Mary , Knowles Cathy
Published: October 2023

This chapter explores accounting for depreciation and bad debts. It highlights the importance of depreciating non-current assets through the straight-line and the reducing-balance methods of providing. Next, the chapter explains the need for providing for bad and doubtful debts. It describes the process of a final adjusted statement of profit or loss and a statement of financial position. The chapter also points out the limits of a statement of financial position by citing historical costs, estimates, judgements, and mining assets. It looks into key accounting concepts such as the entity concept, the money measurement concept, the matching concept, the prudence concept, and the consistency concept.
The Statement of Cash Flows
Authors: Carey Mary , Knowles Cathy
Published: October 2023

This chapter looks into the statement of cash flows. It highlights the importance of cash to a business. Sources of cash flow vary and include operating activities, investing activities, and financing activities. The chapter then differentiates between profit and cash. It shows how working capital is the amount invested in the short-term assets of a business. Additionally, the chapter discusses the process of preparing a statement of cash flows by referencing depreciation and purchasing non-current assets. It cites how companies will often make significant cash payments to pay for tax, interest, and dividends. The chapter also mentions the significance of liquidity.
Interpreting Financial Statements
Authors: Carey Mary , Knowles Cathy
Published: October 2023

This chapter explores financial statements. It looks into types of ratio analysis which is used to highlight underlying trends based on figures from the following areas: profitability, liquidity, and efficiency. The chapter notes the formula in calculating return on capital employed (ROCE) in line with profitability ratios, while the equation for liquidity ratio is focused on assets and liabilities. The chapter discusses the working capital cycle as well. After this, the chapter highlights the importance of care in terms of interpreting ratios. An individual ratio is difficult to analyse without comparison from last year's figures.
Short-term Decision Making
Authors: Carey Mary , Knowles Cathy
Published: October 2023

This chapter focuses on short-term decision making. It cites marginal costing techniques as being relevant in short-term decision making. Decision making is about looking to the future and assessing the impact of a decision. The chapter also looks into the process of organizations buying products by referencing revenues and costs. Then, the chapter looks at the prioritization of products in terms of limited resources. Relevant costs should include only opportunity costs, future, cash, and incremental expenses. The chapter notes when a product should be discontinued or have the location closed by referencing profitability analysis and contribution analysis. The chapter talks about the importance of considering upgrading equipment.
Investment Appraisal Techniques
Authors: Carey Mary , Knowles Cathy
Published: October 2023

This chapter looks into investment appraisal techniques. It explores the nature and significance of appraising long-term investments. Next, the chapter lists the advantages and disadvantages of investment appraisal techniques which are used to assess and compare products. It notes that the accounting rate of return calculates the average annual profit for a project expressed as a percentage return on the average funds invested in the project, while the payback period is the duration of cash inflows from a project covering the initial investment. Additionally, net present value takes into account all cash flows and allows for the time value of money. The chapter also cites the internal rate of return as an investment appraisal technique.
Measuring and Reporting Performance
Authors: Carey Mary , Knowles Cathy
Published: October 2023

This chapter explores the measuring and reporting of performance. It looks into the corporate strategy of businesses as a tool used for setting out long-term plans, while operational plans are more focused on short-term objectives. Additionally, the chapter explores the use of benchmarking to improve performance. It mentions how a balanced scorecard is used to combine non-financial performance with financial data. The chapter also looks into customer profitability analysis, while highlighting the role of integrated reporting, environmental accounting, and carbon reporting. It notes the need for corporate governance as ethical and environmental concerns should be considered.
Case Study: Management Accounting
Authors: Carey Mary , Knowles Cathy
Published: October 2023

Case Study: Management Accounting

Orchid is a personal products company manufacturing shampoo, conditioner, and liquid soap. As it faces tough competition in a static market with no price inflation, the managing director and his team are considering how best to improve its financial performance. They...
Financial Accounting in Context
Authors: Winfield Jimmy , Graham Mark , Miller Taryn
Published: October 2023

This chapter provides an overview of financial accounting. Accounting is the recording and reporting of financial information about an entity. Management accounting and financial accounting both make use of the recording function, but the reporting produced by these two sub-disciplines is very different because the former is intended to inform the decisions of management, while the latter is intended to inform the decisions of existing and potential investors, lenders, and other creditors. The reports generated by financial accounting are called financial statements, and these consist of the statement of financial position, the statement of comprehensive income, the statement of cash flows, and the statement of changes in equity. There are many business forms, including several different types of companies, the most influential of which are typically designated as ‘public interest entities’. These must prepare their annual financial statements according to International Financial Reporting Standards (IFRS).