bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tumors after kidney transplantation: a population study
Authors: Ietto Giuseppe , Gritti Mattia , Pettinato Giuseppe , Carcano Giulio , Gasperina Daniela Dalla 
Published: January 2023

AbstractOne of the main causes of post-transplant-associated morbidity and mortality is cancer. The aims of the project were to study the neoplastic risk within the kidney transplant population and identify the determinants of this risk. A cohort of 462 renal transplant patients from 2010 to 2020 was considered. The expected incidence rates of post-transplant cancer development in the referenced population, the standardized incidence ratios (SIR) taking the Italian population as a comparison, and the absolute risk and the attributable fraction were extrapolated from these cohorts of patients. Kidney transplant recipients had an overall cancer risk of approximately three times that of the local population (SIR 2.8). A significantly increased number of cases were observed for Kaposi’s sarcoma (KS) (SIR 195) and hematological cancers (SIR 6.8). In the first 3 years post-transplant, the risk to develop either KS or hematological cancers was four times higher than in the following years; in all cases of KS, the diagnosis was within 2 years from the transplant. Post-transplant immunosuppression represents the cause of 99% of cases of KS and 85% of cases of lymphomas, while only 39% is represented by solid tumors. Data related to the incidence, the percentages attributable to post-transplant immunosuppression, and the time of onset of neoplasms, particularly for KS and hematological tumors could help improve the management for the follow-up in these patients.
The potential use of mesenchymal stem cells-derived exosomes as microRNAs delivery systems in different diseases
Authors: Oveili Elham , Vafaei Somayeh , Bazavar Haniyeh , Eslami Yeganeh , Mamaghanizadeh Ehsan , Yasamineh Saman , Gholizadeh Omid 
Published: January 2023

AbstractMicroRNAs (miRNAs) are a group of small non-coding RNAs that regulate gene expression by targeting mRNA. Moreover, it has been shown that miRNAs expression are changed in various diseases, such as cancers, autoimmune disease, infectious diseases, and neurodegenerative Diseases. The suppression of miRNA function can be easily attained by utilizing of anti-miRNAs. In contrast, an enhancement in miRNA function can be achieved through the utilization of modified miRNA mimetics. The discovery of appropriate miRNA carriers in the body has become an interesting subject for investigators. Exosomes (EXOs) therapeutic efficiency and safety for transferring different cellular biological components to the recipient cell have attracted significant attention for their capability as miRNA carriers. Mesenchymal stem cells (MSCs) are recognized to generate a wide range of EXOs (MSC-EXOs), showing that MSCs may be effective for EXO generation in a clinically appropriate measure as compared to other cell origins. MSC-EXOs have been widely investigated because of their immune attributes, tumor-homing attributes, and flexible characteristics. In this article, we summarized the features of miRNAs and MSC-EXOs, including production, purification, and miRNA loading methods of MSC-EXOs, and the modification of MSC-EXOs for targeted miRNA delivery in various diseases.
Graphical abstract
Extracellular matrix stiffness mediates uterine repair via the Rap1a/ARHGAP35/RhoA/F-actin/YAP axis
Authors: Zhang Tao , Hu Ruiting , Wang Yan , Guo Shuai , Wu Zhimin , Liu Junfeng , Han Chunyang , Qiu Changwei , Deng Ganzhen 
Published: January 2023

AbstractThe integrity of the structure and function of the endometrium is essential for the maintenance of fertility. However, the repair mechanisms of uterine injury remain largely unknown. Here, we showed that the disturbance of mechanical cue homeostasis occurs after uterine injury. Applying a multimodal approach, we identified YAP as a sensor of biophysical forces that drives endometrial regeneration. Through protein activation level analysis of the combinatorial space of mechanical force strength and of the presence of particular kinase inhibitors and gene silencing reagents, we demonstrated that mechanical cues related to extracellular matrix rigidity can turn off the Rap1a switch, leading to the inactivation of ARHGAP35and then induced activation of RhoA, which in turn depends on the polymerization of the agonist protein F-actin to activate YAP. Further study confirmed that mechanotransduction significantly accelerates remodeling of the uterus by promoting the proliferation of endometrial stromal cells in vitro and in vivo. These studies provide new insights into the dynamic regulatory mechanisms behind uterine remodeling and the function of mechanotransduction.
Panomics reveals patient individuality as the major driver of colorectal cancer progression
Authors: Praus Friederike , Künstner Axel , Sauer Thorben , Kohl Michael , Kern Katharina , Deichmann Steffen , Végvári Ákos , Keck Tobias , Busch Hauke , Habermann Jens K. , Gemoll Timo 
Published: January 2023

Abstract
Background
Colorectal cancer (CRC) is one of the most prevalent cancers, with over one million new cases per year. Overall, prognosis of CRC largely depends on the disease stage and metastatic status. As precision oncology for patients with CRC continues to improve, this study aimed to integrate genomic, transcriptomic, and proteomic analyses to identify significant differences in expression during CRC progression using a unique set of paired patient samples while considering tumour heterogeneity.

Methods
We analysed fresh-frozen tissue samples prepared under strict cryogenic conditions of matched healthy colon mucosa, colorectal carcinoma, and liver metastasis from the same patients. Somatic mutations of known cancer-related genes were analysed using Illumina's TruSeq Amplicon Cancer Panel; the transcriptome was assessed comprehensively using Clariom D microarrays. The global proteome was evaluated by liquid chromatography-coupled mass spectrometry (LC‒MS/MS) and validated by two-dimensional difference in-gel electrophoresis. Subsequent unsupervised principal component clustering, statistical comparisons, and gene set enrichment analyses were calculated based on differential expression results.

Results
Although panomics revealed low RNA and protein expression of CA1, CLCA1, MATN2, AHCYL2, and FCGBP in malignant tissues compared to healthy colon mucosa, no differentially expressed RNA or protein targets were detected between tumour and metastatic tissues. Subsequent intra-patient comparisons revealed highly specific expression differences (e.g., SRSF3, OLFM4, and CEACAM5) associated with patient-specific transcriptomes and proteomes.

Conclusion
Our research results highlight the importance of inter- and intra-tumour heterogeneity as well as individual, patient-paired evaluations for clinical studies. In addition to changes among groups reflecting CRC progression, we identified significant expression differences between normal colon mucosa, primary tumour, and liver metastasis samples from individuals, which might accelerate implementation of precision oncology in the future.
Role of acyl-coenzyme A: cholesterol transferase 1 (ACAT1) in retinal neovascularization
Authors: Zaidi Syed A. H. , Lemtalsi Tahira , Xu Zhimin , Santana Isabella , Sandow Porsche , Labazi Leila , Caldwell Robert W. , Caldwell Ruth B. , Rojas Modesto A. 
Published: January 2023

Abstract
Background
We have investigated the efficacy of a new strategy to limit pathological retinal neovascularization (RNV) during ischemic retinopathy by targeting the cholesterol metabolizing enzyme acyl-coenzyme A: cholesterol transferase 1 (ACAT1). Dyslipidemia and cholesterol accumulation have been strongly implicated in promoting subretinal NV. However, little is known about the role of cholesterol metabolism in RNV. Here, we tested the effects of inhibiting ACAT1 on pathological RNV in the mouse model of oxygen-induced retinopathy (OIR).

Methods
In vivo studies used knockout mice that lack the receptor for LDL cholesterol (LDLR−/−) and wild-type mice. The wild-type mice were treated with a specific inhibitor of ACAT1, K604 (10 mg/kg, i.p) or vehicle (PBS) during OIR. In vitro studies used human microglia exposed to oxygen–glucose deprivation (OGD) and treated with the ACAT1 inhibitor (1 μM) or PBS.

Results
Analysis of OIR retinas showed that increased expression of inflammatory mediators and pathological RNV were associated with significant increases in expression of the LDLR, increased accumulation of neutral lipids, and formation of toxic levels of cholesterol ester (CE). Deletion of the LDLR completely blocked OIR-induced RNV and significantly reduced the AVA. The OIR-induced increase in CE formation was accompanied by significant increases in expression of ACAT1, VEGF and inflammatory factors (TREM1 and MCSF) (p < 0.05). ACAT1 was co-localized with TREM1, MCSF, and macrophage/microglia makers (F4/80 and Iba1) in areas of RNV. Treatment with K604 prevented retinal accumulation of neutral lipids and CE formation, inhibited RNV, and decreased the AVA as compared to controls (p < 0.05). The treatment also blocked upregulation of LDLR, ACAT1, TREM1, MCSF, and inflammatory cytokines but did not alter VEGF expression. K604 treatment of microglia cells also blocked the effects of OGD in increasing expression of ACAT1, TREM1, and MCSF without altering VEGF expression.

Conclusions
OIR-induced RNV is closely associated with increases in lipid accumulation and CE formation along with increased expression of LDLR, ACAT1, TREM1, and MCSF. Inhibiting ACAT1 blocked these effects and limited RNV independently of alterations in VEGF expression. This pathway offers a novel strategy to limit vascular injury during ischemic retinopathy.

Graphical Abstract
Elective adhesiolysis for chronic abdominal pain reduces long-term risk of adhesive small bowel obstruction
Authors: van den Beukel Barend A. W. , Toneman Masja K. , van Veelen Fleur , van Oud-Alblas Marjolein Blusse , van Dongen Koen , Stommel Martijn W. J. , van Goor Harry , ten Broek Richard P. G. 
Published: January 2023

Abstract
Background
Selected patients with adhesion-related chronic abdominal pain can be treated effectively by adhesiolysis with the application of adhesion barriers. These patients might also have an increased risk to develop adhesive small bowel obstruction (ASBO). It is unknown how frequently these patients develop ASBO, and how elective adhesiolysis for pain impacts the risk of ASBO.

Methods
Patients with adhesion-related chronic pain were included in this cohort study with long-term follow-up. The diagnosis of adhesions was confirmed using CineMRI. The decision for operative treatment of adhesions was made by shared agreement based on the correlation of complaints with CineMRI findings. The primary outcome was the 5-years incidence of readmission for ASBO. Incidence was compared between patients with elective adhesiolysis and those treated non-operatively and between patients with and without previous ASBO. Univariable and multivariable Cox regression analysis was performed to identify predictive factors for ASBO. Secondary outcomes included reoperation for ASBO and self-reported pain and other abdominal symptoms.

Results
A total of 122 patients were included, 69 patients underwent elective adhesiolysis. Thirty patients in both groups had previous episodes of ASBO in history. During 5-year follow-up, the readmission rate for ASBO was 6.5% after elective adhesiolysis compared to 26.9% after non-operative treatment (p = 0.012). These percentages were 13.3% compared to 40% in the subgroup of patients with previous episodes of ASBO (p = 0.039). In multivariable analysis, elective adhesiolysis was associated with a decreased risk of readmission for ASBO with an odds ratio of 0.21 (95% CI 0.07–0.65), the risk was increased in patients with previous episodes with a odds ratio of 19.2 (95% CI 2.5–144.4). There was no difference between the groups in the prevalence of self-reported abdominal pain. However, in surgically treated patients the impact of pain on daily activities was lower, and the incidence of other symptoms was lower.

Conclusion
More than one in four patients with chronic adhesion-related pain develop episodes of ASBO when treated non-operatively. Elective adhesiolysis reduces the incidence of ASBO in patients with chronic adhesion-related symptoms, both in patients with and without previous episodes of ASBO in history.
Trial registration The study was registered at Clinicaltrials.gov under NCT01236625.
An atlas of lamina-associated chromatin across twelve human cell types reveals an intermediate chromatin subtype
Authors: Shah Parisha P. , Keough Kathleen C. , Gjoni Ketrin , Santini Garrett T. , Abdill Richard J. , Wickramasinghe Nadeera M. , Dundes Carolyn E. , Karnay Ashley , Chen Angela , Salomon Rachel E. A. , Walsh Patrick J. , Nguyen Son C. , Whalen Sean , Joyce Eric F. , Loh Kyle M. , Dubois Nicole , Pollard Katherine S. , Jain Rajan 
Published: January 2023

Abstract
Background
Association of chromatin with lamin proteins at the nuclear periphery has emerged as a potential mechanism to coordinate cell type-specific gene expression and maintain cellular identity via gene silencing. Unlike many histone modifications and chromatin-associated proteins, lamina-associated domains (LADs) are mapped genome-wide in relatively few genetically normal human cell types, which limits our understanding of the role peripheral chromatin plays in development and disease.

Results
To address this gap, we map LAMIN B1 occupancy across twelve human cell types encompassing pluripotent stem cells, intermediate progenitors, and differentiated cells from all three germ layers. Integrative analyses of this atlas with gene expression and repressive histone modification maps reveal that lamina-associated chromatin in all twelve cell types is organized into at least two subtypes defined by differences in LAMIN B1 occupancy, gene expression, chromatin accessibility, transposable elements, replication timing, and radial positioning. Imaging of fluorescently labeled DNA in single cells validates these subtypes and shows radial positioning of LADs with higher LAMIN B1 occupancy and heterochromatic histone modifications primarily embedded within the lamina. In contrast, the second subtype of lamina-associated chromatin is relatively gene dense, accessible, dynamic across development, and positioned adjacent to the lamina. Most genes gain or lose LAMIN B1 occupancy consistent with cell types along developmental trajectories; however, we also identify examples where the enhancer, but not the gene body and promoter, changes LAD state.

Conclusions
Altogether, this atlas represents the largest resource to date for peripheral chromatin organization studies and reveals an intermediate chromatin subtype.
Update to the study protocol Face Your Fears: Virtual reality-based cognitive behavioral therapy (VR-CBT) versus standard CBT for paranoid ideations in patients with schizophrenia spectrum disorders: a randomized clinical trial
Authors: Jeppesen U. N. , Due A. S. , Mariegaard L. , Pinkham A. , Vos M. , Veling W. , Nordentoft M. , Glenthøj L. B. 
Published: January 2023

AbstractWe unfortunately need to make an update to our published study protocol that describes a significant change in the design of the study. The Committee on Health Research Ethics of the Capital Region Denmark recently rejected the approval of changing the primary outcome in the trial, on the invariable grounds that the trial has already commenced. It is therefore necessary to retain the Green Paranoid Thought Scale (GPTS) part B, ideas of persecution, as our primary outcome, and GPTS part A, ideas of social reference, as a secondary outcome, which is described opposite in our published study protocol. The exchange of outcomes has not affected participation in our trial or the informed consent. Intervention in both groups and assessments are unchanged. The two outcomes together constitute GPTS and the unifying concept we attempt to treat, namely paranoid ideations. As this is a blinded, methodologically rigorous trial, we did not have—and still do not have—access to preliminary data, and therefore, we have no knowledge of the distribution of our two intervention groups nor the potential effect of the intervention. The power calculation remains unchanged irrespective of the selection of the primary outcome. We have been fully transparent with the changes in primary and secondary outcomes on ClinicalTrials.gov throughout the trial. Due to the considerations mentioned above, we assumed that there would not be any ethical implications of the change of primary outcome. We sincerely apologize for the irregularity caused because of this assumption.Trial registrationClinicalTrials.gov NCT04902066. Initial release April 19th, 2021.
The influence of receptor expression and clinical subtypes on baseline [18F]FDG uptake in breast cancer: systematic review and meta-analysis
Authors: de Mooij Cornelis M. , Ploumen Roxanne A. W. , Nelemans Patty J. , Mottaghy Felix M. , Smidt Marjolein L. , van Nijnatten Thiemo J. A. 
Published: January 2023

Abstract
Background
To quantify the relationship between [18F]FDG uptake of the primary tumour measured by PET-imaging with immunohistochemical (IHC) expression of ER, PR, HER2, Ki-67, and clinical subtypes based on these markers in breast cancer patients.

Methods
PubMed and Embase were searched for studies that compared SUVmax between breast cancer patients negative and positive for IHC expression of ER, PR, HER2, Ki-67, and clinical subtypes based on these markers. Two reviewers independently screened the studies and extracted the data. Standardized mean differences (SMD) and 95% confidence intervals (CIs) were estimated by using DerSimonian-Laird random-effects models. P values less than or equal to 5% indicated statistically significant results.

Results
Fifty studies were included in the final analysis. SUVmax is significantly higher in ER-negative (31 studies, SMD 0.66, 0.56–0.77, P < 0.0001), PR-negative (30 studies, SMD 0.56; 0.40–0.71, P < 0.0001), HER2-positive (32 studies, SMD − 0.29, − 0.49 to − 0.10, P = 0.0043) or Ki-67-positive (19 studies, SMD − 0.77; − 0.93 to − 0.61, P < 0.0001) primary tumours compared to their counterparts. The majority of clinical subtypes were either luminal A (LA), luminal B (LB), HER2-positive or triple negative breast cancer (TNBC). LA is associated with significantly lower SUVmax compared to LB (11 studies, SMD − 0.49, − 0.68 to − 0.31, P = 0.0001), HER2-positive (15 studies, SMD − 0.91, − 1.21 to − 0.61, P < 0.0001) and TNBC (17 studies, SMD − 1.21, − 1.57 to − 0.85, P < 0.0001); and LB showed significantly lower uptake compared to TNBC (10 studies, SMD − 0.77, − 1.05 to − 0.49, P = 0.0002). Differences in SUVmax between LB and HER2-positive (9 studies, SMD − 0.32, − 0.88 to 0.24, P = 0.2244), and HER2-positive and TNBC (17 studies, SMD − 0.29, − 0.61 to 0.02, P = 0.0667) are not significant.

Conclusion
Primary tumour SUVmax is significantly higher in ER-negative, PR-negative, HER2-positive and Ki-67-positive breast cancer patients. Luminal tumours have the lowest and TNBC tumours the highest SUVmax. HER2 overexpression has an intermediate effect.
Extremely boosted neural network for more accurate multi-stage Cyber attack prediction in cloud computing environment
Authors: Dalal Surjeet , Manoharan Poongodi , Lilhore Umesh Kumar , Seth Bijeta , Mohammed alsekait Deema , Simaiya Sarita , Hamdi Mounir , Raahemifar Kaamran 
Published: January 2023

AbstractThere is an increase in cyberattacks directed at the network behind firewalls. An all-inclusive approach is proposed in this assessment to deal with the problem of identifying new, complicated threats and the appropriate countermeasures. In particular, zero-day attacks and multi-step assaults, which are made up of a number of different phases, some malicious and others benign, illustrate this problem well. In this paper, we propose a highly Boosted Neural Network to detect the multi-stageattack scenario. This paper demonstrated the results of executing various machine learning algorithms and proposed an enormously boosted neural network. The accuracy level achieved in the prediction of multi-stage cyber attacks is 94.09% (Quest Model), 97.29% (Bayesian Network), and 99.09% (Neural Network). The evaluation results of the Multi-Step Cyber-Attack Dataset (MSCAD) show that the proposed Extremely Boosted Neural Network can predict the multi-stage cyber attack with 99.72% accuracy. Such accurate prediction plays a vital role in managing cyber attacks in real-time communication.
Enhanced correlation-based linking of biosynthetic gene clusters to their metabolic products through chemical class matching
Authors: Louwen Joris J. R. , Medema Marnix H. , van der Hooft Justin J. J. 
Published: January 2023

Abstract
Background
It is well-known that the microbiome produces a myriad of specialised metabolites with diverse functions. To better characterise their structures and identify their producers in complex samples, integrative genome and metabolome mining is becoming increasingly popular. Metabologenomic co-occurrence-based correlation scoring methods facilitate the linking of metabolite mass fragmentation spectra (MS/MS) to their cognate biosynthetic gene clusters (BGCs) based on shared absence/presence patterns of metabolites and BGCs in paired omics datasets of multiple strains. Recently, these methods have been made more readily accessible through the NPLinker platform. However, co-occurrence-based approaches usually result in too many candidate links to manually validate. To address this issue, we introduce a generic feature-based correlation method that matches chemical compound classes between BGCs and MS/MS spectra.

Results
To automatically reduce the long lists of potential BGC-MS/MS spectrum links, we match natural product (NP) ontologies previously independently developed for genomics and metabolomics and developed NPClassScore: an empirical class matching score that we also implemented in the NPLinker platform. By applying NPClassScore on three paired omics datasets totalling 189 bacterial strains, we show that the number of links is reduced by on average 63% as compared to using a co-occurrence-based strategy alone. We further demonstrate that 96% of experimentally validated links in these datasets are retained and prioritised when using NPClassScore.

Conclusion
The matching genome-metabolome class ontologies provide a starting point for selecting plausible candidates for BGCs and MS/MS spectra based on matching chemical compound class ontologies. NPClassScore expedites genome/metabolome data integration, as relevant BGC-metabolite links are prioritised, and researchers are faced with substantially fewer proposed BGC-MS/MS links to manually inspect. We anticipate that our addition to the NPLinker platform will aid integrative omics mining workflows in discovering novel NPs and understanding complex metabolic interactions in the microbiome.