bluuebunny/crossref_metadata_2025_split huggingface dataset:
Using explainable machine learning to uncover the kinase–substrate interaction landscape
Authors: Zhou Zhongliang , Yeung Wayland , Soleymani Saber , Gravel Nathan , Salcedo Mariah , Li Sheng , Kannan Natarajan 
Published: January 2024

Abstract

Motivation
Phosphorylation, a post-translational modification regulated by protein kinase enzymes, plays an essential role in almost all cellular processes. Understanding how each of the nearly 500 human protein kinases selectively phosphorylates their substrates is a foundational challenge in bioinformatics and cell signaling. Although deep learning models have been a popular means to predict kinase–substrate relationships, existing models often lack interpretability and are trained on datasets skewed toward a subset of well-studied kinases.

Results
Here we leverage recent peptide library datasets generated to determine substrate specificity profiles of 300 serine/threonine kinases to develop an explainable Transformer model for kinase–peptide interaction prediction. The model, trained solely on primary sequences, achieved state-of-the-art performance. Its unique multitask learning paradigm built within the model enables predictions on virtually any kinase–peptide pair, including predictions on 139 kinases not used in peptide library screens. Furthermore, we employed explainable machine learning methods to elucidate the model’s inner workings. Through analysis of learned embeddings at different training stages, we demonstrate that the model employs a unique strategy of substrate prediction considering both substrate motif patterns and kinase evolutionary features. SHapley Additive exPlanation (SHAP) analysis reveals key specificity determining residues in the peptide sequence. Finally, we provide a web interface for predicting kinase–substrate associations for user-defined sequences and a resource for visualizing the learned kinase–substrate associations.

Availability and implementation
All code and data are available at https://github.com/esbgkannan/Phosformer-ST. Web server is available at https://phosformer.netlify.app.
2dGBH: Two-dimensional group Benjamini–Hochberg procedure for false discovery rate control in two-way multiple testing of genomic data
Authors: Yang Lu , Wang Pei , Chen Jun 
Published: January 2024

AbstractMotivationEmerging omics technologies have introduced a two-way grouping structure in multiple testing, as seen in single-cell omics data, where the features can be grouped by either genes or cell types. Traditional multiple testing methods have limited ability to exploit such two-way grouping structure, leading to potential power loss.ResultsWe propose a new 2D Group Benjamini–Hochberg (2dGBH) procedure to harness the two-way grouping structure in omics data, extending the traditional one-way adaptive GBH procedure. Using both simulated and real datasets, we show that 2dGBH effectively controls the false discovery rate across biologically relevant settings, and it is more powerful than the BH or q-value procedure and more robust than the one-way adaptive GBH procedure.Availability and implementation2dGBH is available as an R package at: https://github.com/chloelulu/tdGBH. The analysis code and data are available at: https://github.com/chloelulu/tdGBH-paper.
Efficient nonparametric estimation of Toeplitz covariance matrices
Authors: Klockmann K , Krivobokova T 
Published: January 2024

Abstract
A new efficient nonparametric estimator for Toeplitz covariance matrices is proposed. This estimator is based on a data transformation that translates the problem of Toeplitz covariance matrix estimation to the problem of mean estimation in an approximate Gaussian regression. The resulting Toeplitz covariance matrix estimator is positive definite by construction, fully data driven and computationally very fast. Moreover, this estimator is shown to be minimax optimal under the spectral norm for a large class of Toeplitz matrices. These results are readily extended to estimation of inverses of Toeplitz covariance matrices. Also, an alternative version of the Whittle likelihood for the spectral density based on the discrete cosine transform is proposed.
State-of-the-art for contrast-enhanced mammography
Authors: Covington Matthew F , Salmon Samantha , Weaver Bradley D , Fajardo Laurie L 
Published: January 2024

Abstract
Contrast-enhanced mammography (CEM) is an emerging breast imaging technology with promise for breast cancer screening, diagnosis, and procedural guidance. However, best uses of CEM in comparison with other breast imaging modalities such as tomosynthesis, ultrasound, and MRI remain inconclusive in many clinical settings. This review article summarizes recent peer-reviewed literature, emphasizing retrospective reviews, prospective clinical trials, and meta-analyses published from 2020 to 2023. The intent of this article is to supplement prior comprehensive reviews and summarize the current state-of-the-art of CEM.
Enhancing quality assurance in radiotherapy for gynaecological cancers: implementation of an on-demand peer review process
Authors: Bhattacharyya Tapesh , Chakraborty Santam , Achari Rimpa Basu , Mallick Indranil , Arunsingh Moses , Shenoy Shashank , Harilal Vishnu , Phesao Vezokhoto , Maulik Shaurav , Manjunath Nisarga Vontikoppal , Mukherjee Prattusha , Sarkar Nivedita , Sinha Avinaba , Sarkar Sebanti , Vashistha Bhanu , Khanum Hashmath , Chatterjee Sanjoy 
Published: January 2024

Abstract

Objectives
Ensuring high-quality radiotherapy requires peer-reviewing target volumes. The Royal College of Radiologists recommends peer review specifically for individual target volumes in cases of gynaecological cancers. This study presents the outcomes of implementing an on-demand peer review system for gynaecological cancers within our institute.

Methods
The peer review process was planned for gynaecological cancer cases intended for curative radiotherapy. After junior clinical oncologists (COs) completed the segmentation, two senior COs specializing in gynaecological cancers conducted the peer review. All peer review outcomes were recorded prospectively. The audit process compliance, the proportion of patients requiring major and minor modifications in target volumes, the direction of changes, and the factors influencing these changes were reported.

Results
A total of 230 patients were eligible, and out of these, 204 (88.3%) patients underwent at least one peer review. Among the patients, 108 required major modifications in their target volumes. P-charts revealed a stabilization in the need for major modifications at the end of three months, indicating that 38.2% and 28% of patients still required major modifications for the nodal and primary CTV, respectively. Multivariable analysis demonstrated that major modifications were associated with the use of extended field radiotherapy and radical radiation in non-cervical primary cases.

Conclusions
An on-demand peer review system was feasible and resulted in clinically meaningful, major modifications in the target volumes for 53% of patients.

Advances in knowledge
Gynaecological cancers require ongoing peer review to ensure quality of care in radiotherapy. A flexible on-demand system not only ensures that patient treatment start is not delayed but also has an important educational role for junior trainees.
Racemose neurocysticercosis: a case series
Authors: Sharma Srishti , Singh Anuradha , Mani Vinita Elizabeth , Mishra Sarvesh Chandra , Chaturvedi Pragya , Jain Shweta , Kumar Sunil , Jain Neeraj 
Published: January 2024

Abstract
Neurocysticercosis (NCC) is a common parasitic condition of the central nervous system in certain parts of the world. The racemose variety of NCC is distinct from the commonly seen parenchymal form. It frequently infiltrates the basal cisterns and Sylvian fissures. Imaging plays a vital role in the diagnosis; however, as their signal intensity is similar to cerebrospinal fluid and due to the absence of enhancement in most cases, imaging diagnosis is often difficult on the conventional MRI sequences. Here, we present five cases of racemose NCC to emphasize the importance of a heavily T2-weighted sequence (Fast Imaging Employing Steady-state Acquisition) sequence in the diagnosing this entity.
Maximizing aged photovoltaic array power: a computer modelling study
Authors: Sibai Fadi N 
Published: January 2024

Abstract
Photovoltaic (PV) modules age with time for various reasons such as corroded joints and terminals and glass coating defects, and their ageing degrades the PV array power. With the help of the PV array numerical model, this paper explores the effects of PV module ageing on the PV array power, and the power gains and costs of rearranging and recabling aged PV modules in a PV array. The numerical PV array model is first revised to account for module ageing, rearrangement and recabling, with the relevant equations presented herein. The updated numerical model is then used to obtain the array powers for seven different PV arrays. The power results are then analysed in view of the attributes of the seven PV array examples. A guiding method to recommend recabling after rearranging aged modules is then proposed, leading to further significant power gains, while eliminating intra-row mismatches. When certain conditions are met, it was shown that recabling PV modules after rearranging them may lead to further significant power gains, reaching 57% and 98% in two considered PV array examples. Higher gains are possible in other arrays. A cost–benefit analysis weighing annual power gains versus estimated recabling costs is also given for the seven considered PV array examples to guide recabling decisions based on technical and economic merits. In the considered examples, recabling costs can be recovered in &lt;4 years. Compared with the powers of the aged arrays, power gains due to our proposed rearranging and recabling the PV arrays ranged between 73% and 131% in the considered examples—well over the gains reported in the literature. Moreover, the cost of our static module rearrangement and recabling method outshines the costs of dynamic reconfiguration methods recently published in the literature.
Organoids as a tool to study the impact of heterogeneity in gastrointestinal epithelium on host–pathogen interactions
Authors: Paužuolis Mindaugas , Samperio Ventayol Pilar , Neyazi Mastura , Bartfeld Sina 
Published: January 2024

Summary
The epithelium of the gastrointestinal (GI) tract has been extensively characterized using advanced histological and RNA sequencing techniques, which has revealed great cellular diversity. Pathogens, such as viruses and bacteria, are highly adapted to their host and often exhibit not only species-specificity but also a preference or tropism for specific GI segments or even cell types—some of these preferences are so specific, that these pathogens still cannot be cultured invitro. Organoid technology now provides a tool to generate human cell types, which enables the study of host cell tropism. Focussing on the GI tract, we provide an overview about cellular differentiation in vivo and in organoids and how differentiation in organoids and their derived models is used to advance our understanding of viral, bacterial, and parasitic infection. We emphasize that it is central to understand the composition of the model, as the alteration of culture conditions yields different cell types which affects infection. We examine future directions for wider application of cellular heterogeneity and potential advanced model systems for GI tract infection studies.
Basis of executive functions in fine-grained architecture of cortical and subcortical human brain networks
Authors: Assem Moataz , Shashidhara Sneha , Glasser Matthew F , Duncan John 
Published: January 2024

Abstract
Theoretical models suggest that executive functions rely on both domain-general and domain-specific processes. Supporting this view, prior brain imaging studies have revealed that executive activations converge and diverge within broadly characterized brain networks. However, the lack of precise anatomical mappings has impeded our understanding of the interplay between domain-general and domain-specific processes. To address this challenge, we used the high-resolution multimodal magnetic resonance imaging approach of the Human Connectome Project to scan participants performing 3 canonical executive tasks: n-back, rule switching, and stop signal. The results reveal that, at the individual level, different executive activations converge within 9 domain-general territories distributed in frontal, parietal, and temporal cortices. Each task exhibits a unique topography characterized by finely detailed activation gradients within domain-general territory shifted toward adjacent resting-state networks; n-back activations shift toward the default mode, rule switching toward dorsal attention, and stop signal toward cingulo-opercular networks. Importantly, the strongest activations arise at multimodal neurobiological definitions of network borders. Matching results are seen in circumscribed regions of the caudate nucleus, thalamus, and cerebellum. The shifting peaks of local gradients at the intersection of task-specific networks provide a novel mechanistic insight into how partially-specialized networks interact with neighboring domain-general territories to generate distinct executive functions.
Dynamic reconfiguration of brain coactivation states that underlying working memory correlates with cognitive decline in clinically unimpaired older adults
Authors: Li Linling , Chen Zaili , Zhang Li , Zhang Min , Liu Honghai , Wu Donghui , Ren Ping , Zhang Zhiguo 
Published: January 2024

Abstract
Impairments in working memory (WM) are evident in both clinically diagnosed patients with mild cognitive decline and older adults at risk, as indicated by lower scores on neuropsychological tests. Examining the WM-related neural signatures in at-risk older adults becomes essential for timely intervention. WM functioning relies on dynamic brain activities, particularly within the frontoparietal system. However, it remains unclear whether the cognitive decline would be reflected in the decreased dynamic reconfiguration of brain coactivation states during WM tasks. We enrolled 47 older adults and assessed their cognitive function using the Montreal Cognitive Assessment. The temporal dynamics of brain coactivations during a WM task were investigated through graph-based time-frame modularity analysis. Four primary recurring states emerged: two task-positive states with positive activity in the frontoparietal system (dorsal attention and central executive); two task-negative states with positive activity in the default mode network accompanied by negative activity in the frontoparietal networks. Heightened WM load was associated with increased flexibility of the frontoparietal networks, but the cognitive decline was correlated with reduced capacity for neuroplastic changes in response to increased task demands. These findings advance our understanding of aberrant brain reconfiguration linked to cognitive decline, potentially aiding early identification of at-risk individuals.
Potentially modifiable factors associated with health-related quality of life among people with chronic kidney disease: baseline findings from the National Unified Renal Translational Research Enterprise CKD (NURTuRE-CKD) cohort
Authors: Phillips Thomas , Harris Scott , Aiyegbusi Olalekan Lee , Lucas Bethany , Benavente Melissa , Roderick Paul J , Cockwell Paul , Kalra Philip A , Wheeler David C , Taal Maarten W , Fraser Simon D S 
Published: January 2024

ABSTRACT

Background
Many non-modifiable factors are associated with poorer health-related quality of life (HRQoL) experienced by people with chronic kidney disease (CKD). We hypothesize that potentially modifiable factors for poor HRQoL can be identified among CKD patients, providing potential targets for intervention.

Method
The National Unified Renal Translational Research Enterprise Chronic Kidney Disease (NURTuRE-CKD) cohort study recruited 2996 participants from nephrology centres with all stages of non-dialysis-dependent CKD. Baseline data collection for sociodemographic, anthropometric, biochemical and clinical information, including Integrated Palliative care Outcome Scale renal, Hospital Anxiety and Depression score (HADS) and the 5-level EuroQol-5D (EQ-5D-5L) as HRQoL measure, took place between 2017 and 2019. EQ-5D-5L dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression) were mapped to an EQ-5D-3L value set to derive index value. Multivariable mixed effects regression models, adjusted for known factors affecting HRQoL with recruitment region as a random effect, were fit to assess potentially modifiable factors associated with index value (linear) and within each dimension (logistic).

Results
Among the 2958/2996 (98.7%) participants with complete EQ-5D data, 2201 (74.4%) reported problems in at least one EQ-5D-5L dimension. Multivariable linear regression identified independent associations between poorer HRQoL (EQ-5D-3L index value) and obesity (body mass index ≥30.0 kg/m2, β −0.037, 95% CI −0.058 to −0.016, P = .001), HADS depression score ≥8 (β −0.159, −0.182 to −0.137, P &lt; .001), anxiety score ≥8 (β −0.090, −0.110 to −0.069, P &lt; .001), taking ≥10 medications (β −0.065, −0.085 to −0.046, P &lt; .001), sarcopenia (β −0.062, −0.080 to −0.043, P &lt; .001) haemoglobin &lt;100 g/L (β −0.047, −0.085 to −0.010, P = .012) and pain (β −0.134, −0.152 to −0.117, P &lt; .001). Smoking and prescription of prednisolone independently associated with problems in self-care and usual activities respectively. Renin–angiotensin system inhibitor (RASi) prescription associated with fewer problems with mobility and usual activities.

Conclusion
Potentially modifiable factors including obesity, pain, depression, anxiety, anaemia, polypharmacy, smoking, steroid use and sarcopenia associated with poorer HRQoL in this cohort, whilst RASi use was associated with better HRQoL in two dimensions.
Comparison of three creatinine-based equations to predict adverse outcome in a cardiovascular high-risk cohort: an investigation using the SPRINT research materials
Authors: Emrich Insa E , Pickering John W , Götzinger Felix , Kramann Rafael , Kunz Michael , Lauder Lucas , Papademetriou Vasilios , Böhm Michael , Heine Gunnar H , Mahfoud Felix 
Published: January 2024

ABSTRACT

Background
Novel creatinine-based equations have recently been proposed but their predictive performance for cardiovascular outcomes in participants at high cardiovascular risk in comparison to the established CKD-EPI 2009 equation is unknown.

Method
In 9361 participants from the United States included in the randomized controlled SPRINT trial, we calculated baseline estimated glomerular filtration rate (eGFR) using the CKD-EPI 2009, CKD-EPI 2021, and EKFC equations and compared their predictive value of cardiovascular events. The statistical metric used is the net reclassification improvement (NRI) presented separately for those with and those without events.

Results
During a mean follow-up of 3.1 ± 0.9 years, the primary endpoint occurred in 559 participants (6.0%). When using the CKD-EPI 2009, the CKD-EPI 2021, and the EKFC equations, the prevalence of CKD (eGFR &lt;60 ml/min/1.73 m2 or &gt;60 ml/min/1.73 m2 with an ACR ≥30 mg/g) was 37% vs. 35.3% (P = 0.02) vs. 46.4% (P &lt; 0.001), respectively. The corresponding mean eGFR was 72.5 ± 20.1 ml/min/1.73 m2 vs. 73.2 ± 19.4 ml/min/1.73 m2 (P &lt; 0.001) vs. 64.6 ± 17.4 ml/min/1.73 m2 (P &lt; 0.001). Neither reclassification according to the CKD-EPI 2021 equation [CKD-EPI 2021 vs. CKD-EPI 2009: NRIevents: −9.5% (95% confidence interval (CI) −13.0% to −5.9%); NRInonevents: 4.8% (95% CI 3.9% to 5.7%)], nor reclassification according to the EKFC equation allowed better prediction of cardiovascular events compared to the CKD-EPI 2009 equation (EKFC vs. CKD-EPI 2009: NRIevents: 31.2% (95% CI 27.5% to 35.0%); NRInonevents: −31.1% (95% CI −32.1% to −30.1%)).

Conclusion
Substituting the CKD-EPI 2009 with the CKD-EPI 2021 or the EKFC equation for calculation of eGFR in participants with high cardiovascular risk without diabetes changed the prevalence of CKD but was not associated with improved risk prediction of cardiovascular events for both those with and without the event.
Association Between Smoking Status and the Efficacy and Safety of Tofacitinib in Patients with Ulcerative Colitis
Authors: Rubin David T , Torres Joana , Regueiro Miguel , Reinisch Walter , Prideaux Lani , Kotze Paulo G , Tan Fiona H , Gardiner Sean , Mundayat Rajiv , Cadatal Mary Jane , Ng Siew C 
Published: January 2024

Abstract

Background
Tofacitinib is an oral Janus kinase inhibitor for the treatment of ulcerative colitis (UC). This analysis assessed the impact of cigarette smoking on tofacitinib efficacy and safety in the UC clinical program.

Methods
Efficacy endpoints and adverse events (AEs) were evaluated by smoking status (ever smokers [current and ex-smokers] and never smokers) in the phase (P)2 induction study (baseline demographics and safety only), P3 studies (OCTAVE Induction 1&2, OCTAVE Sustain, OCTAVE Open), and P3/4b RIVETING study.

Results
This post hoc analysis included 1156 patients (ever smokers, n = 416 [36.0%; current smokers, n = 59 (5.1%); ex-smokers, n = 357 (30.9%)]; never smokers, n = 740 [64.0%]; median [range] treatment duration 654 [1–2712] and 615.5 [1–2850] days, respectively). Similar proportions of ever smokers and never smokers achieved efficacy endpoints. AEs were reported in 88.7% of ever smokers and 83.8% of never smokers. Overall, 60.6% of ever smokers had an infection (serious infections, 5.5%; herpes zoster [nonserious and serious], 10.8%; Clostridioides difficile infection, 12.0%; lower respiratory tract infection, 19.5%: corresponding values among never smokers were 53.1%, 3.9%, 6.8%, 8.5%, and 11.4%). Major adverse cardiovascular events were reported in 1.0% of ever smokers and 0.7% of never smokers and thromboembolism events (venous and arterial) in 1.0% of ever smokers and 0.9% never smokers. Deaths, malignancies (excluding non-melanoma skin cancer [NMSC]), and NMSC occurred infrequently in ever smokers (0.5%, 2.5%, and 3.7%, respectively) and never smokers (0.1%, 1.5%, and 1.0%, respectively). Colorectal cancer was reported in 0.6% of never smokers; no cases occurred in ever smokers.

Conclusions
Efficacy and safety of tofacitinib were generally similar in ever smokers and never smokers. Overall, serious AEs and, as expected, infections were more frequent in ever smokers versus never smokers. This may inform treatment selection and monitoring strategies.

ClinicalTrials.gov
NCT00787202;NCT01465763;NCT01458951;NCT01458574;NCT01470612;NCT03281304