bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of endometrial embryokines on the preimplantation bovine embryo to create a gene expression signature consistent with a high competence phenotype
Authors: Maldonado Mariângela Bueno Cordeiro , Rabaglino Maria Belen , Cannon Gabrielle Heather , Hansen Peter James 
Published: January 2025

Abstract
Optimal embryonic development depends upon cell-signaling molecules released by the maternal reproductive tract called embryokines. The identity of specific embryokines that enhance the competence of the embryo for sustained survival is largely lacking. The current objective was to evaluate the effects of three putative embryokines in cattle on embryonic development to the blastocyst stage. The molecules tested were vascular endothelial growth factor A (VEGFA), C-X-C motif chemokine ligand 12 (CXCL12), and interleukin-6 (IL6). Molecules were added from day 4 to 7.5 of culture at 50 ng/mL (VEGFA and CXCL12) or 100 ng/mL (IL6). Endpoints were development to the blastocyst stage and transcript abundance for 94 specific genes involved in lineage commitment, epigenetic regulation, and other functions. Among the genes examined were eight whose transcript abundance has been related to embryo competence for survival after embryo transfer. None of the molecules increased the proportion of putative zygotes or cleaved embryos becoming blastocysts at day 7.5 of development. An embryo competence index based on a Bayesian multiple regression formula to weigh transcript abundance of the eight biomarker genes was not affected by treatment with VEGFA but was increased by both CXCL12 and IL6. The transcript abundance of 5 genes was modified by VEGFA, 19 by CXCL12, and 19 by IL6. A total of 11 genes were modified in a similar manner by CXCL12 and IL6. Most differentially expressed genes for CXCL12 and IL6 were downregulated, suggesting that the embryokines may promote a less energetically demanding metabolic state than would be the case in their absence.
White matter connections within the central sulcus subserving the somato-cognitive action network
Authors: Skandalakis Georgios P , Viganò Luca , Neudorfer Clemens , Rossi Marco , Fornia Luca , Cerri Gabriella , Kinsman Kelsey P , Bajouri Zabiullah , Tavakkoli Armin D , Koutsarnakis Christos , Lani Evgenia , Komaitis Spyridon , Stranjalis George , Zadeh Gelareh , Barrios-Martinez Jessica , Yeh Fang-Cheng , Serletis Demitre , Kogan Michael , Hadjipanayis Constantinos G , Hong Jennifer , Simmons Nathan , Gordon Evan M , Dosenbach Nico U F , Horn Andreas , Bello Lorenzo , Kalyvas Aristotelis , Evans Linton T 
Published: January 2025

Abstract
The somato-cognitive action network (SCAN) consists of three nodes interspersed within Penfield’s motor effector regions. The configuration of the somato-cognitive action network nodes resembles the one of the ‘plis de passage’ of the central sulcus: small gyri bridging the precentral and postcentral gyri. Thus, we hypothesize that these may provide a structural substrate of the somato-cognitive action network.
Using microdissections of 16 human hemispheres, we consistently identified a chain of three distinct plis de passage with increased underlying white matter in locations analogous to the somato-cognitive action network nodes. We mapped localizations of plis de passage into standard stereotactic space to seed functional MRI connectivity across 9000 resting-state functional MRI scans, which demonstrated the connectivity of these sites with the somato-cognitive action network. Intraoperative recordings during direct electrical central sulcus stimulation further identified inter-effector regions corresponding to plis de passage locations.
This work provides a critical step towards an improved understanding of the somato-cognitive action network in both structural and functional terms. Furthermore, our work has the potential to guide the development of refined motor cortex stimulation techniques for treating brain disorders and operative resective techniques for complex surgery of the motor cortex.
Cortical involvement of lateral trunk flexion and verticality misperception in Parkinson’s disease
Authors: Kohsaka Masayuki , Oeda Tomoko , Takaya Shigetoshi , Tomita Satoshi , Park Kwiyoung , Yamamoto Kenji , Fukuyama Hidenao , Sawada Hideyuki 
Published: January 2025

Abstract
Lateral trunk flexion is a common form of postural abnormality in Parkinson’s disease and could be associated with verticality misperception. However, the mechanisms underlying lateral trunk flexion and verticality misperception in Parkinson’s disease remain unclear. In the current study, we examined whether lateral trunk flexion is associated with verticality misperception in patients with Parkinson’s disease. We also identified the brain regions involved in lateral trunk flexion and altered verticality perception. In this cross-sectional study, we evaluated the verticality perception using the subjective visual vertical test in 81 patients with Parkinson’s disease and 14 age-matched healthy controls. According to the 97.5th percentile upper reference limit of the body tilt angle in the healthy controls, patients with Parkinson’s disease were grouped into 37 patients with lateral trunk flexion and 44 patients without lateral trunk flexion. The mean of absolute subjective visual vertical angles was compared between patients with Parkinson’s disease with lateral trunk flexion, those without lateral trunk flexion, and the healthy controls, and the impact of verticality misperception on lateral trunk flexion was evaluated using multivariate logistic regression models. We further performed a voxel-wise comparison of regional cerebral blood flow using N-isopropyl-p-[123I] iodoamphetamine single-photon emission computed tomography (height threshold of P &lt; 0.001, uncorrected for multiple comparisons, extent threshold of 100 voxels) to identify the brain regions associated with lateral trunk flexion, and to investigate the relationship between verticality misperception and regional hypoperfusion. The mean of absolute subjective visual vertical angles was larger in patients with Parkinson’s disease with and without lateral trunk flexion than in healthy controls (P &lt; 0.001 and P &lt; 0.001). Additionally, the subjective visual vertical angle was associated with the presence of lateral trunk flexion (odds ratio 2.25, 95% confidence interval 1.51–3.36, P &lt; 0.001). The regional cerebral blood flow in patients with Parkinson’s disease with lateral trunk flexion was decreased in the right inferior parietal lobule, right superior parietal lobule, right superior temporal gyrus, and right dorsal posterior cingulate cortex compared with those without lateral trunk flexion. The subjective visual vertical angle was inversely correlated with regional cerebral blood flow in these regions, except for the dorsal posterior cingulate cortex. Our study reveals that hypofunction in the right temporoparietal association cortices is involved in verticality misperception and the development of lateral trunk flexion in patients with Parkinson’s disease. These results provide insights into potential therapeutic targets for addressing lateral trunk flexion.
Optimizing arrhythmia identification using chaos theory and deep learning analysis
Authors: Eldakhly Nabil M 
Published: January 2025

Abstract
Optimal heart function is crucial for quality life. Electrocardiograms are indispensable for diagnosing cardiac irregularities and analyzing heartbeat signals. This study unveils three novel machine learning (ML) techniques enhancing diagnostic precision. The first method scrutinizes raw ECG data and its time-series metrics, while the second incorporates historical patient health data for direct ECG classification. The third technique transforms ECG signals into insightful features, focusing on QRS complex waves. Uniquely combining these strategies, our research pioneers in advanced feature selection for cardiac diagnosis. Experiments were conducted to compare the integration of clinical data, QRS characteristics, and chaos preprocessing impact on the diagnosis. For classification assessment, five algorithms were utilized: Support Vector Machine, Decision Tree, Naïve Bayes, Neural Network, and Convolutional Neural Networks (CNNs). Implementing chaos theory, we converted QRS features into deterministic metrics. Notably, our Chaos-Enhanced CNN model exhibited outstanding performance, achieving a remarkable 99.8% accuracy rate, outshining other models.
Certolizumab Pegol Treatment in Patients With Crohn’s Disease: Final Safety Data From the SECURE Registry
Authors: Lichtenstein Gary R , Lee Scott D , Feagan Brian G , Loftus Edward V , Ng Samson , Dehlin Kaitlin , Quinn Paul , Coarse Jason , Rosario-Jansen Theresa , Arendt Catherine , Stark Jeffrey L 
Published: January 2025

Abstract

Background
Crohn’s disease (CD) treatment is associated with increased risks of infection and malignancies. Although the safety of certolizumab pegol (CZP) is well established, long-term data from community-based observational studies are lacking.

Aim
This study aimed to evaluate long-term safety outcomes of patients from the SECURE registry receiving CZP relative to other CD treatments, including corticosteroids, immunosuppressants, and biologics. The primary outcome of this observational study was the evaluation of malignancies.

Methods
Adult patients with CD were prospectively monitored for up to 8 years. Pre-specified data were collected for all enrolled patients. Adverse events of interest (AEoIs) were reported per 100 patient-years (PY) of exposure. Incidence rate ratios (IRRs) were calculated for AEoIs using multivariate regression analysis accounting for exposure to multiple treatments. Malignancies reported after any exposure to CZP were attributed to CZP. Post-hoc analyses were conducted to evaluate non-melanoma skin cancer (NMSC), lymphoma, and pregnancy outcomes.

Results
A total of 3072 patients were enrolled in the study. The risk of AEoIs was similar between patients with only CZP exposure versus comparator exposure. Among patients with any CZP exposure, there was a higher frequency of serious infections (IRR: 2.56 [95% confidence interval (CI): 2.00, 3.29]) and hypersensitivity or anaphylactic reactions (IRR: 4.11 [95% CI: 1.80, 9.38]) versus patients with comparator exposure. Malignancy rates were similar across groups; however, concomitant use of thiopurines was associated with higher odds of NMSC (odds ratio: 2.30 [95% CI: 1.09, 4.89]). Most cases of lymphoma (5/7) occurred in patients with exposure to thiopurines. Pregnancy outcomes were similar across groups.

Conclusions
No new safety signals were identified for CZP; the use of thiopurines was identified as a risk factor for NMSC.

Trial registration
NCT00844285.
Prognostic significance of subcarinal lymph node involvement in patients with Siewert type I and II gastro-esophageal junctional adenocarcinoma: an analysis of 698 patients undergoing Ivor-Lewis esophagectomy
Authors: Walmsley James A , Abdelrahman Mohamed , Ariyarathenam Arun , Berrisford Richard , Humphreys Lee , Sanders Grant , Tham Ji Chung , Wheatley Tim , Chan David S Y 
Published: January 2025

Summary
Gastro-esophageal junction (GOJ) adenocarcinoma is increasingly common and despite significant changes in management over the past decade, overall survival remains poor. Determining factors that influence survival is important for optimizing curative surgery. The prognostic significance of subcarinal lymph node involvement is unclear. The purpose of this study was to assess the prognostic significance of subcarinal lymph node involvement in patients undergoing curative resection of GOJ adenocarcinoma. Consecutive patients undergoing curative 2-stage Ivor-Lewis esophagectomy between February 2010 and January 2022 were analyzed retrospectively from a prospectively maintained database for Siewert type I and II GOJ adenocarcinoma confirmed on histopathology. Outcomes were compared based on subcarinal node involvement confirmed on histopathology. A total of 698 patients with Siewert type I (n = 314) and II (n = 384) adenocarcinoma were analyzed [median age 68 (31–85), 604 males (87%) neo-adjuvant use 491 (74.4%)]. Eighteen patients (2.6%) had subcarinal lymph node involvement. These patients had more advanced overall stage of disease and positive node involvement than those without and a significantly lower median survival of 6 months (&lt;1–25) compared to 53 months (41–65) (p &lt; 0.001). On multivariate analysis, pathological T stage, para-gastric and subcarinal lymph node involvement were found to be the independent and significant factors influencing survival. Subcarinal lymph node involvement is an indicator of advanced disease and high positive node burden. It is an independent prognostic factor in patients undergoing curative surgery for Siewert type I and II GOJ adenocarcinoma.
Impact of a personalized, strike early and strong lipid-lowering approach on low-density lipoprotein-cholesterol levels and cardiovascular outcome in patients with acute myocardial infarction
Authors: Patti Giuseppe , Cumitini Luca , Bosco Manuel , Marengo Alessandra , D'Amario Domenico , Mennuni Marco , Solli Martina , Grisafi Leonardo 
Published: January 2025

Abstract

Aims
Considering the lack of evidence, we evaluated the impact on cardiovascular outcome of the systematic introduction in our institution of a personalized strike early and strong (SES) approach for lipid-lowering therapy (LLT) in patients admitted for acute myocardial infarction (MI).

Methods and results
We retrospectively analysed data from 500 consecutive patients hospitalized across three periods: Period A (N = 198, January–June 2019), when the low-density lipoprotein cholesterol (LDL-C) goal was &lt;70 mg/dL and a stepwise LLT approach was recommended; Period B (N = 180, January–June 2021), when the LDL-C goal was &lt;55 mg/dL and a stepwise approach was recommended; Period C (N = 122, January–June 2023), when the LDL-C goal was &lt;55 mg/dL and our SES protocol was implemented. Primary endpoints were achievement of the LDL-C goal during follow-up and 1-year incidence of major adverse cardiovascular events (MACE). Compared to the other periods, in Period C, there was a higher use of potent statins, alone or in combination with ezetimibe, and of proprotein convertase subtilisin/kexin type 9 inhibitor inhibitors at discharge. This translated into higher achievement of the LDL-C goal (83% vs. 55% in Period A and 43% in Period B; P &lt; 0.001) and reduced incidence of MACE (3% vs. 12% and 11%; P = 0.026). MACE rates were lowest in patients with early and sustained LDL-C &lt;55 mg/dL and in those achieving both LDL-C &lt;55 mg/dL and ≥50% LDL-C reduction.

Conclusion
The systematic introduction of a personalized, SES strategy for LLT in patients with acute MI led to greater achievement of LDL-C goal and lower risk of MACE at 1 year vs. the stepwise approach.
Prognostic value of computed tomography-derived myocardial extracellular volume in aortic stenosis: a meta-analysis of all-cause mortality and heart failure hospitalization
Authors: Kirigaya Jin , Kato Shingo , Matsushita Kensuke , Horita Nobuyuki , Utsunomiya Daisuke , Hibi Kiyoshi 
Published: January 2025

Abstract

Aims
Pre-existing myocardial fibrosis before aortic valve replacement (AVR) is a major cause of postoperative heart failure (HF). Evaluation of fibrosis by computed tomography extracellular volume (CT-ECV) may allow risk stratification for patients with severe aortic stenosis (AS) scheduled for transaortic AVR (TAVR) or surgical AVR (SAVR). We performed a meta-analysis to determine the prognostic value of CT-ECV for the prediction of adverse events in patients with severe AS scheduled for AVR.

Methods and results
Electronic database searches of PubMed, Web of Science Core Collection, Cochrane advanced search, and EMBASE were performed. A comprehensive literature review was conducted to examine the association between CT-ECV and prognosis in patients with severe AS who underwent AVR. The diagnostic performance of CT-ECV for predicting composite adverse events (all-cause death and hospitalization for HF) was assessed using a pooled odds ratio (OR). Data from 902 patients with severe AS were extracted from six studies, including 881 TAVR and 21 SAVR cases. The pooled OR of abnormal CT-ECV for predicting adverse events was 4.53 [95% confidence interval (CI): 3.13–6.57 (I2 = 10%, P for heterogeneity = 0.50)]. We performed an OR meta-analysis on five studies with only TAVR cases (n = 807). The pooled OR of abnormal CT-ECV for predicting adverse events in TAVR patients was 4.85 [95% CI: 3.26–7.21 (I² = 0%, P &lt; 0.001)].

Conclusion
Considering the high prognostic ability and versatility of CT-ECV, it may be used to predict postoperative adverse events in patients with severe AS who underwent AVR.
Impact of cardiac position, morphology and operative technique on long-term Fontan outcomes in heterotaxy
Authors: Kadowaki Sachiko , Fan Chun-Po Steve , Zahiri Yasmin , Yap Kok Hooi , Tocharoenchok Teerapong , Dipchand Anne I , Honjo Osami , Barron David J 
Published: January 2025

Abstract

OBJECTIVES
This study aimed to assess the outcomes of heterotaxy patients who underwent the Fontan operation, focusing on morphological features and surgical techniques.

METHODS
Eighty-two consecutive heterotaxy patients who underwent the Fontan operation from 1985 to 2021 were compared to 150 patients with tricuspid atresia (TA) and 144 patients with hypoplastic left heart syndrome (HLHS). The Kaplan–Meier method and Cox proportional hazard model were used to analyse transplant-free survival and predictor of outcomes.

RESULTS
The 20-year transplant-free survival rates were comparable between right atrial isomerism (RAI, n = 45) and left atrial isomerism (LAI, n = 37) [RAI versus LAI, 76% (95% confidence interval, 57–87%) vs 68% (47–82%), P = 0.22], although more pulmonary vein interventions at Fontan were needed in RAI. Surgical techniques included extracardiac conduit in 66%, intra-atrial conduit in 9% and lateral tunnel in 18% of the cases. Cardiac position and apicocaval juxtaposition did not influence outcomes, but the inferior vena cava (IVC)-contralateral pulmonary artery (PA) Fontan was associated with 100% survival, while the IVC-ipsilateral PA Fontan at the cardiac apex showed a 67% (34–87%) survival rate at 20 years. In-hospital mortality was higher in heterotaxy [9.8% (5–19%)] compared to TA [1.3% (0.3–5.3%), P&lt;0.01) and HLHS [2.8% (1.1–7.3%), P = 0.02], with no early death after 2000 in any group. The 20-year transplant-free survival in heterotaxy [72% (59–82%)] was similar to that in HLHS [80% (69–87%), P = 0.11].

CONCLUSIONS
Various routing techniques can be successfully applied to overcome anatomical challenges in heterotaxy. Despite higher in-hospital mortality, overall survival was similar to HLHS. RAI had comparable survival to LAI with more pulmonary vein interventions at Fontan.
One-minute sit-to-stand test cut-offs for risk stratification based on six-minute walk test thresholds in pulmonary hypertension
Authors: Kronberger Christina , Mousavi Roya Anahita , Ermolaev Nikita , Willixhofer Robin , Rassoulpour Nima , Kaya Musa Bedirxan , Poledniczek Michael , Eslami Mahshid , Krall Christoph , Litschauer Brigitte , Grzeda Mariusz Tadeusz , McKenna Ian , Badr Eslam Roza 
Published: January 2025

Abstract

Aims
We aimed to establish 1-min sit-to-stand test (1-min STST) cut-off values that align with the guideline-recommended 6-min walk test (6MWT) thresholds (165 and 440 m) for 1-year mortality risk stratification in pulmonary hypertension (PH) patients. Furthermore, we aimed to compare clinical characteristics and long-term mortality among patients stratified by these proposed 1-min STST cut-offs.

Methods and results
All patients performed the 1-min STST and 6MWT. Receiver operating characteristics analysis was performed to determine 1-min STST cut-offs corresponding to the 6MWT thresholds. Patients were stratified into three groups based on these cut-offs. Among 114 PH patients (mean age 66 ± 14 years, 57% female), the mean number of 1-min STST repetitions was 17 ± 6 and the mean 6MWT distance was 354 ± 133 m. The aligning 1-min STST cut-off for the &lt;165 m 6MWT threshold was 14 repetitions (sensitivity 69%; specificity 100%) with an area under the curve (AUC) of 0.90 [95% confidence interval (CI) 0.84–0.97]. For the &gt;440 m threshold, 20 repetitions (sensitivity 81%; specificity 84%) aligned with an AUC of 0.85 (95% CI 0.75–0.94). Patients performing ≤14 repetitions had worse N-terminal prohormone of brain natriuretic peptide levels (P &lt; 0.001), World Health Organization functional class (P &lt; 0.001), mean pulmonary artery pressure (P = 0.050), and health-related quality of life (P &lt; 0.001) and a higher rate of mortality than those performing ≥20 repetitions (P = 0.020).

Conclusion
The 1-min STST cut-offs aligning with the 6MWT thresholds of 165 and 440 m are 14 and 20 repetitions, respectively. Patients performing ≤14 repetitions demonstrated worse clinical parameters and higher mortality rates, making the 1-min STST a potential risk stratification tool in PH patients.

Lay summary
This study identified cut-off values for the 1-min sit-to-stand test (1-min STST) that align with the 6-min walk test (6MWT) thresholds used to predict 1-year mortality risk in pulmonary hypertension (PH) patients, proposing the 1-min STST as a practical alternative for risk stratification.
Management of intrahepatic cholangiocarcinoma: a review for clinicians
Authors: Colangelo Matteo , Di Martino Marcello , Polidoro Michela Anna , Forti Laura , Tober Nastassja , Gennari Alessandra , Pagano Nico , Donadon Matteo 
Published: January 2025

Abstract
Intrahepatic cholangiocarcinoma (iCCA) is an aggressive liver malignancy that arises from second-order biliary epithelial cells. Its incidence is gradually increasing worldwide. Well-known risk factors have been described, although in many cases, they are not identifiable. Treatment options are continuously expanding, but the prognosis of iCCA remains dismal. R0 liver resection remains the only curative treatment, but only a limited number of patients can benefit from it. Frequently, major hepatectomies are needed to completely remove the tumour. This could contraindicate surgery or increase postoperative morbidity in patients with chronic liver disease and small remnant liver volume. In cases of anticipated inadequate future liver remnant, regenerative techniques may be used to expand resectability. The role and extent of lymphadenectomy in iCCA are still matters of debate. Improvements in iCCA diagnosis and better understanding of genetic profiles might lead to optimized surgical approaches and drug therapies. The role of neoadjuvant and adjuvant therapies is broadening, gaining more and more acceptance in clinical practice. Combining surgery with locoregional therapies and novel drugs, such as checkpoint-inhibitors and molecular-targeted molecules, might improve treatment options and survival rates. Liver transplantation, after very poor initial results, is now receiving attention for the treatment of patients with unresectable very early iCCA (i.e. &lt;2 cm) in cirrhotic livers, showing survival outcomes comparable to those of hepatocellular carcinoma. Ongoing prospective protocols are testing the efficacy of liver transplantation for patients with unresectable, advanced tumours confined to the liver, with sustained response to neoadjuvant treatment. In such a continuously changing landscape, the aim of our work is to review the state-of-the-art in the surgical and medical treatment of iCCA.