bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of polyp regression and reduction on treatment efficacy in polypoidal choroidal vasculopathy treated with aflibercept
Authors: Sayanagi Kaori , Fujimoto Satoko , Hara Chikako , Fukushima Yoko , Maruyama Kazuichi , Kawasaki Ryo , Sato Shigeru , Nishida Kohji
Published: January 2024

Intravitreal injection of aflibercept (IVA) has successfully treated polypoidal choroidal vasculopathy (PCV), and polyp morphology is an important indicator of treatment efficacy. However, many studies have not reported the presence or absence of polyp regression and treatment outcomes, and few studies have reported polyp reduction and treatment outcomes in cases with residual polyps. We retrospectively measured the polyp area on indocyanine green angiography images before and after the IVA loading phase and investigated the regression and reduction of polyps and treatment outcomes of 81 eyes with PCV treated with IVA. We investigated the relationship between the presence or absence of complete regression of polyps and the percentage change in the polyp area and treatment outcomes. Eyes with complete polyp regression had significantly better visual acuity improvements compared with baseline at 12 months (P = 0.0108), fewer treatments (P = 0.0024), fewer recurrences during 12-months follow-up (P = 0.0010), and more “dry maculas” at 3 months (P = 0.0048) than eyes in which polyp regression did not occur. A significant correlation was seen only between the percentage of polyp regression and visual acuity at 3 months (P = 0.0395). Regarding IVA therapy for PCV, the presence or absence of complete polyp regression at the end of the loading phase affected the treatment outcome, whereas the degree of polyp reduction in cases of residual polyps had no effect.
Effects of Enterococcus faecium (R8a) on nonspecific immune gene expression, immunity and intestinal flora of giant tiger shrimp (Penaeus monodon)
Authors: Sun Xueliang , Fang Zhenzhen , Yu Hong , Zhao Honghao , Wang Yang , Zhou Falin , Zhao Lin , Sun Jingfeng , Tian Yunchen
Published: January 2024

In this study, Penaeus monodon were gave basic feed supplemented with three levels of Enterococcus faecium. Then, the expression of non-specific immunity-related genes, and the activities of total antioxidant capacity (T-AOC), superoxide dismutase (SOD), malondialdehyde (MDA), acid phosphatase (ACP), alkaline phosphatase (AKP), phenol oxidase (PO) were evaluated. Meanwhile, the disease resistance test and intestinal flora determination were conducted. The results showed that the MDA levels of 2% and 5% E. faecium groups were significantly lower than that of the control group (P < 0.05). While the SOD and T-AOC and ACP and AKP of experimental groups were significantly higher (P < 0.05), the PO of experimental groups were significantly lower than that of the control group (P < 0.05). In addition, the expressions of immunity-related genes (tlr22, dorsal, lysozyme, crustin, imd, and relish) in the 2% and 5% E. faecalis groups were significantly greater than those in the control group (P < 0.05). After P. monodon was challenged with Vibrio parahaemolyticus for 7 days, the average cumulative mortality of P. monodon in the 2% and 5% groups were significantly lower than that in the 0% group (P < 0.05). With the increase of feeding time, the number of effective OTUs in each group showed a downward trend. At the 14th d, Proteobacteria, Bacteroidetes and Firmicutes, the dominant flora in the intestinal tract of P. monodon. In summary, supplied with E. faecium could increase the expression of non-specific immunity-related genes, enhance the immune capacity of P. monodon.
Solid-state mechanochemistry for the rapid and efficient synthesis of tris-cyclometalated iridium(iii) complexes
Authors: Kubota Koji , Endo Tsubura , Ito Hajime
Published: January 2024

A two-step mechanochemical protocol using ball milling enables the rapid and efficient synthesis of various tris-cyclometalated iridium(iii) complexes without the use of significant amounts of organic solvent in air.
Piezoelectric dressings for advanced wound healing
Authors: Dai Jinjun , Shao Jin , Zhang Yi , Hang Ruiyue , Yao Xiaohong , Bai Long , Hang Ruiqiang
Published: January 2024

The treatment of chronic refractory wounds poses significant challenges and threats to both human society and the economy.
Role of extracellular polymeric substances in selenite and tellurite reduction by waste activated and anaerobic sludge
Authors: Saikia Sudeshna , Pakshirajan Kannan , Lens Piet N. L.
Published: January 2024

Simultaneous reduction and formation of EPS derived Se and Te NPs in individual and conjugated forms.
Retraction Note: Where Do Deceased Children Go? A Spiritual View
Authors: Çaksen Hüseyin
Published: January 2024

Retraction

An investigation by the publisher found a number of articles, including this one, published in Journal of Child Science in Volume 12, Number 01, e146–e147, on October 07, 2022 (DOI: 10.1055/s-0042-1757145), with a number of concerns, including but not limited to undeclared conflicts of interest and manipulated peer review procedures. As a result, the publisher has retracted and removed this article.
Reforming allied health service provision in residential aged care to improve the rehabilitation reach: a feasibility study
Authors: Brusco Natasha , Ekegren Christina , Rawson Helen , Taylor Nicholas F. , Morphet Julia , Hill Keith , Anderson Jennifer , Stephen Kelly , Crabtree Amelia , Levinger Pazit , Whittaker Sara L. , Soh Sze-Ee , Dulfer Fiona , Lawler Katherine
Published: January 2024

Objective My Therapy is an allied health guided, co-designed rehabilitation self-management program for residents of aged care facilities. This study aimed to determine the feasibility of implementing My Therapy in a residential aged care setting. Methods This observational study was conducted on a 30-bed wing, within a 90-bed metropolitan residential aged care facility, attached to a public health service, in Victoria, Australia. Staff and resident data were collected prospectively over 6 weeks (staff focus groups, patient surveys, and audits) to evaluate the feasibility domains of acceptability, reach and demand, practicality, integration, limited efficacy testing and adaptations. Results Twenty-six residents and five allied health staff (physiotherapy and occupational therapy) participated. My Therapy was acceptable to residents (survey) and staff (focus groups). Via initial My Therapy discussions between the resident and the therapists, to determine goals and resident preferences, My Therapy reached 26 residents (n = 26/26, 100% program reach), with 15 residents subsequently receiving a rehabilitation program (n = 15/26, 58% program demand). The remaining 11 residents did not participate due to resident preference or safety issues (n = 11/26, 42%). Collecting physical function outcome measures for limited efficacy testing was practical, and the cost of My Therapy was AUD$6 per resident per day, suggesting financial integration may be possible. Several adaptations were required, due to limited allied health staff, complex resident goal setting and program co-design. Conclusion My Therapy has the potential to improve the rehabilitation reach of allied health services in residential aged care. While introducing this low-cost intervention is feasible, adaptations were required for successful implementation.
Medicare Benefits Schedule (MBS) Review Advisory Committee post-implementation review of MBS telehealth items: abolition of initial telehealth consultations for non-general practitioner specialists
Authors: Looi Jeffrey C. L. , Allison Stephen , Bastiampillai Tarun , Kisely Steve , Pring William
Published: January 2024

In 2022, the Australian Federal Minister for Health and Aged Care commissioned the Medicare Benefits Schedule (MBS) Review Advisory Committee (MRAC) to conduct a post-implementation review of MBS telehealth services, including settings of video and telephone consultations. The MRAC has made a series of administrative recommendations for telehealth practice that appear at cross-purposes to the evidence-base on medical consultations and that would limit patient access to medical specialist assessment in Australia. These recommendations particularly underestimate the role of telehealth in rural and remote Australia and did not take into account high patient satisfaction with telehealth assessment and treatment during the ongoing coronavirus disease 2019 (COVID-19) pandemic. They also appear to contradict the Medical Board of Australia’s guidance on telehealth. On this basis, the recommendations for telehealth principles and abolition of reimbursement for telehealth for all initial non-general practitioner medical specialist consultations should be withdrawn.
Soil seed bank dynamics of two invasive alien plants in Nigeria: implications for ecosystem restoration
Authors: Akomolafe Gbenga F , Rosazlina Rusly , Omomoh Bernard
Published: January 2024

The assessment of seed banks could provide useful hints towards ensuring restoration planning and invasive species management. In this study, the impacts of two invaders such as Hyptis suaveolens and Urena lobata on the soil seed banks were investigated. We also assessed the seed characteristics of the invaders at the invaded sites. This was achieved using 10 sites each for H. suaveolens- and U. lobata-invaded habitats and -non-invaded habitats making a total of 30 sites. We collected 200 soil samples from each habitat type. A seedling emergence method was used to determine the seed bank recruitment of both invasive plants. The diversity indices of the above-ground vegetation of sites invaded by the two plants were significantly lower than those of the non-invaded sites. Only two plant species emerged from the seed banks of H. suaveolens and five plants from those of U. lobata when compared with non-invaded sites where 53 species emerged. A larger portion of the seeds was located in the soil’s lower layer at all the sites invaded by H. suaveolens while those of U. lobata and non-invaded sites were found in the upper layers and there are significant associations between the habitats. The lower soil layers of the two species have the highest percentage of viable seeds. These results help us to understand more about the invasiveness of both species as related to their impacts on the seed banks and native vegetation. It also indicates that the native species that emerged from the invaded seed banks could be used for the restoration of the invaded habitats.
SL-Miner: a web server for mining evidence and prioritization of cancer-specific synthetic lethality
Authors: Liu Xin , Hu Jieni , Zheng Jie
Published: January 2024

Synthetic lethality (SL) refers to a type of genetic interaction in which the simultaneous inactivation of two genes leads to cell death, while the inactivation of a single gene does not affect cell viability. It significantly expands the range of potential therapeutic targets for anti-cancer treatments. SL interactions are primarily identified through experimental screening and computational prediction. Although various computational methods have been proposed, they tend to ignore providing evidence to support their predictions of SL. Besides, they are rarely user-friendly for biologists who likely have limited programming skills. Moreover, the genetic context specificity of SL interactions is often not taken into consideration. Here, we introduce a web server called SL-Miner, which is designed to mine the evidence of SL relationships between a primary gene and a few candidate SL partner genes in a specific type of cancer, and to prioritize these candidate genes by integrating various types of evidence. For intuitive data visualization, SL-Miner provides a range of charts (e.g. volcano plot and box plot) to help users get insights from the data.

Availability and implementation

SL-Miner is available at https://slminer.sist.shanghaitech.edu.cn.
QATS: an ImageJ plugin for the quantification of toroidal nuclei in biological images
Authors: Pons Carles , Mauvezin Caroline
Published: January 2024

Motivation

The toroidal nucleus is a novel chromosomal instability (CIN) biomarker which complements the micronucleus. Understanding the specific biological stresses leading to the formation of each CIN-associated phenotype requires the evaluation of large panels of biological images collected from different genetic backgrounds and environmental conditions. However, the quantification of toroidal nuclei is currently a manual process which is unviable on a large scale.

Results

Here, we present QATS (QuAntification of Toroidal nuclei in biological imageS), a tool that automates the identification of toroidal nuclei, minimizing false positives while highly agreeing with the manual quantifications. Additionally, QATS identifies micronuclei for a convenient comparison of both CIN biomarkers. QATS is an open-source ImageJ plugin with a user-friendly interface that enables a wide scientific community to easily assess the frequency of CIN biomarkers for the determination of CIN levels in cellular models.

Availability and implementation

QATS is an ImageJ plugin freely available at http://www.toroidalnucleus.org/qats. The user manual and the images used for the evaluation of QATS are included in the website. Supplementary data are available at Bioinformatics online.
Conumee 2.0: enhanced copy-number variation analysis from DNA methylation arrays for humans and mice
Authors: Daenekas Bjarne , Pérez Eilís , Boniolo Fabio , Stefan Sabina , Benfatto Salvatore , Sill Martin , Sturm Dominik , Jones David T W , Capper David , Zapatka Marc , Hovestadt Volker
Published: January 2024

Motivation

Copy-number variations (CNVs) are common genetic alterations in cancer and their detection may impact tumor classification and therapeutic decisions. However, detection of clinically relevant large and focal CNVs remains challenging when sample material or resources are limited. This has motivated us to create a software tool to infer CNVs from DNA methylation arrays which are often generated as part of clinical routines and in research settings.

Results

We present our R package, conumee 2.0, that combines tangent normalization, an adjustable genomic binning heuristic, and weighted circular binary segmentation to utilize DNA methylation arrays for CNV analysis and mitigate technical biases and batch effects. Segmentation results were validated in a lung squamous cell carcinoma dataset from TCGA (n = 367 samples) by comparison to segmentations derived from genotyping arrays (Pearson’s correlation coefficient of 0.91). We further introduce a segmented block bootstrapping approach to detect focal alternations that achieved 60.9% sensitivity and 98.6% specificity for deletions affecting CDKN2A/B (60.0% and 96.9% for RB1, respectively) in a low-grade glioma cohort from TCGA (n = 239 samples). Finally, our tool provides functionality to detect and summarize CNVs across large sample cohorts.

Availability and implementation

Conumee 2.0 is available under open-source license at: https://github.com/hovestadtlab/conumee2.
Insights into the inner workings of transformer models for protein function prediction
Authors: Wenzel Markus , Grüner Erik , Strodthoff Nils
Published: January 2024

Motivation

We explored how explainable artificial intelligence (XAI) can help to shed light into the inner workings of neural networks for protein function prediction, by extending the widely used XAI method of integrated gradients such that latent representations inside of transformer models, which were finetuned to Gene Ontology term and Enzyme Commission number prediction, can be inspected too.

Results

The approach enabled us to identify amino acids in the sequences that the transformers pay particular attention to, and to show that these relevant sequence parts reflect expectations from biology and chemistry, both in the embedding layer and inside of the model, where we identified transformer heads with a statistically significant correspondence of attribution maps with ground truth sequence annotations (e.g. transmembrane regions, active sites) across many proteins.

Availability and Implementation

Source code can be accessed at https://github.com/markuswenzel/xai-proteins.
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

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

Motivation

Emerging 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.

Results

We 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 implementation

2dGBH 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

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

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

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

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

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 <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

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

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

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

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 < .001), anxiety score ≥8 (β −0.090, −0.110 to −0.069, P < .001), taking ≥10 medications (β −0.065, −0.085 to −0.046, P < .001), sarcopenia (β −0.062, −0.080 to −0.043, P < .001) haemoglobin <100 g/L (β −0.047, −0.085 to −0.010, P = .012) and pain (β −0.134, −0.152 to −0.117, P < .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

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 <60 ml/min/1.73 m2 or >60 ml/min/1.73 m2 with an ACR ≥30 mg/g) was 37% vs. 35.3% (P = 0.02) vs. 46.4% (P < 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 < 0.001) vs. 64.6 ± 17.4 ml/min/1.73 m2 (P < 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

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
Comparison of Endoscopic and Artificial Intelligence Diagnoses for Predicting the Histological Healing of Ulcerative Colitis in a Real-World Clinical Setting
Authors: Omori Teppei , Yamamoto Tomoko , Murasugi Shun , Koroku Miki , Yonezawa Maria , Nonaka Kouichi , Nagashima Yoji , Nakamura Shinichi , Tokushige Katsutoshi
Published: January 2024

Background

Artificial intelligence (AI)-assisted colonoscopy systems with contact microscopy capabilities have been reported previously; however, no studies regarding the clinical use of a commercially available system in patients with ulcerative colitis (UC) have been reported. In this study, the diagnostic performance of an AI-assisted ultra-magnifying colonoscopy system for histological healing was compared with that of conventional light non-magnifying endoscopic evaluation in patients with UC.

Methods

The data of 52 patients with UC were retrospectively analyzed. The Mayo endoscopic score (MES) was determined by 3 endoscopists. Using the AI system, healing of the same spot assessed via MES was defined as a predicted Geboes score (GS) < 3.1. The GS was then determined using pathology specimens from the same site.

Results

A total of 191 sites were evaluated, including 159 with a GS < 3.1. The MES diagnosis identified 130 sites as MES0. A total of 120 sites were determined to have healed based on AI. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of MES0 for the diagnosis of GS < 3.1 were 79.2%, 90.6%, 97.7%, 46.8%, and 81.2%, respectively. The AI system performed similarly to MES for the diagnosis of GS < 3.1: sensitivity, 74.2%; specificity: 93.8%; PPV: 98.3%; NPV: 42.3%; and accuracy: 77.5%. The AI system also significantly identified a GS of < 3.1 in the setting of MES1 (P = .0169).

Conclusions

The histological diagnostic yield the MES- and AI-assisted diagnoses was comparable. Healing decisions using AI may avoid the need for histological examinations.
Analysis and review of techniques and tools based on machine learning and deep learning for prediction of lysine malonylation sites in protein sequences
Authors: Ramazi Shahin , Tabatabaei Seyed Amir Hossein , Khalili Elham , Nia Amirhossein Golshan , Motarjem Kiomars
Published: January 2024

The post-translational modifications occur as crucial molecular regulatory mechanisms utilized to regulate diverse cellular processes. Malonylation of proteins, a reversible post-translational modification of lysine/k residues, is linked to a variety of biological functions, such as cellular regulation and pathogenesis. This modification plays a crucial role in metabolic pathways, mitochondrial functions, fatty acid oxidation and other life processes. However, accurately identifying malonylation sites is crucial to understand the molecular mechanism of malonylation, and the experimental identification can be a challenging and costly task. Recently, approaches based on machine learning (ML) have been suggested to address this issue. It has been demonstrated that these procedures improve accuracy while lowering costs and time constraints. However, these approaches also have specific shortcomings, including inappropriate feature extraction out of protein sequences, high-dimensional features and inefficient underlying classifiers. As a result, there is an urgent need for effective predictors and calculation methods. In this study, we provide a comprehensive analysis and review of existing prediction models, tools and benchmark datasets for predicting malonylation sites in protein sequences followed by a comparison study. The review consists of the specifications of benchmark datasets, explanation of features and encoding methods, descriptions of the predictions approaches and their embedding ML or deep learning models and the description and comparison of the existing tools in this domain. To evaluate and compare the prediction capability of the tools, a new bunch of data has been extracted based on the most updated database and the tools have been assessed based on the extracted data. Finally, a hybrid architecture consisting of several classifiers including classical ML models and a deep learning model has been proposed to ensemble the prediction results. This approach demonstrates the better performance in comparison with all prediction tools included in this study (the source codes of the models presented in this manuscript are available in https://github.com/Malonylation).

Database URL: https://github.com/A-Golshan/Malonylation
The chromosome-level genome of the submerged plantCryptocoryne crispatulaprovides insights into the terrestrial–freshwater transition in Araceae
Authors: Qian Zhi-Hao , Li Wei , Wang Qing-Feng , Liang Shi-Chu , Wu Shuang , Li Zhi-Zhong , Chen Jin-Ming
Published: January 2024

Plant terrestrialization (i.e. the transition to a terrestrial environment) is a significant evolutionary event that has been intensively studied. While certain plant lineages, particularly in angiosperms, have re-adapted to freshwater habitats after colonizing terrene, however, the molecular mechanism of the terrestrial–freshwater (T–F) transition remains limited. Here, the basal monocot Araceae was selected as the study object to explore the T–F transition adaptation mechanism by comparative genomic analysis. Our findings revealed that the substitution rates significantly increased in the lineage of freshwater Araceae, which may promote their adaptation to the freshwater habitat. Additionally, 20 gene sets across all four freshwater species displayed signs of positive selection contributing to tissue development and defense responses in freshwater plants. Comparative synteny analysis showed that genes specific to submerged plants were enriched in cellular respiration and photosynthesis. In contrast, floating plants were involved in regulating gene expression, suggesting that gene and genome duplications may provide the original material for plants to adapt to the freshwater environment. Our study provides valuable insights into the genomic aspects of the transition from terrestrial to aquatic environments in Araceae, laying the groundwork for future research in the angiosperm.
In-gallery social behaviors of the ambrosia beetle, Xylosandrus germanus (Coleoptera: Curculionidae)
Authors: Milbrath Lindsey R , Biazzo Jeromy , Mudrak Erika
Published: January 2024

The east Asian ambrosia beetle Xylosandrus germanus (Blanford) was first detected in the United States in 1932. It now occurs across much of eastern North America and parts of the Pacific Northwest. It attacks a broad range of stressed, woody hosts including ornamental and orchard species. The foundress tunnels into the sapwood of hosts where it cultures a symbiotic fungus as food for its offspring. A few other ambrosia beetles have been shown to possess a facultatively eusocial structure among gallery members, but this has not been described for Xylosandrus spp. Using a novel artificial diet arena, we quantified the behaviors of X. germanus larvae and adults (foundress and mature offspring) over 10 wk inside their galleries. Foundresses were responsible for constructing the gallery. They also initially tended the fungal garden and brood but eventually spent most of their time blocking the gallery entrance. Larvae were mainly observed to feed, crawl, or be inactive within the gallery, regardless of the absence or presence of adult siblings. Adult female offspring were primarily inactive, likely due to dormancy. Adult male offspring actively crawled and attempted to mate with their sisters before eventually dispersing out of the gallery. Cooperative hygienic behaviors (removal of frass, cannibalism of dead nest mates, grooming siblings) were observed but a division of labor among offspring was not clear. Rather, foundress behaviors were mostly distinct from offspring behaviors, particularly as the gallery aged. Because no overlap in generations occurred, X. germanus displays a quasisocial structure.