bluuebunny/crossref_metadata_2025_split huggingface dataset:
ANKRD29, as a new prognostic and immunological biomarker of non–small cell lung cancer, inhibits cell growth and migration by regulating MAPK signaling pathway
Authors: Zhao Hanqing , Wang Yanbo , He Yaomei , Zhang Peng , Zeng Cheng , Du Tongxuan , Shen Qiushuo , Zhao Song 
Published: June 2023

Abstract
Background
The predominant cancer-related deaths worldwide are caused by lung cancer, particularly non-small cell lung cancer (NSCLC), despite the fact that numerous therapeutic initiatives have been devised to improve the outcomes. Ankyrin repeat domain (ANKRD) is one of the widespread protein structural motifs in eukaryotes but the functions of ANKRD proteins in NSCLC progression remains unclear.

Methods
We performed integrative bioinformatical analysis to determine the dysregulated expression of ANKRDs in multiple tumors and the association between ANKRD29 expression and the NSCLC tumor environment. Quantitative real-time PCR (qRT-PCR), western blot, immunohistochemistry (IHC), and tissue microarray (TMA) assays were used to investigate the expression of ANKRD29 in NSCLC cell lines. The role of ANKRD29 in NSCLC cell proliferation and migration in vitro was deteceted by 5-bromodeoxyuridine (BrdU) incorporation, colony formation, flow cytometry, would-healing, trans-well, and western blot experiment. RNA-seq technology was applied to deciper the molecular mechanism regulated by ANKRD29 in NSCLC.

Results
We constructed a valuable risk-score system for predicting the overall survival outcomes of NSCLC patients based on the expression of five hub ANKRD genes. And we found that the hub gene ANKRD29 was remarkedly decreased in NSCLC tissues and cell lines due to the promoter hypermethylation, and revealed that high ANKRD29 expression obviously correlated with patients’ better clinical outcome. Overexpression of ANKRD29 significantly inhibited cell proliferation and migration, promoted the cancerous cells’ sensitivity to carboplatin and enhanced the killing ability of T cells in NSCLC cells. Interestingly, ANKRD29 can be served as a biomarker to predict the response to immunotherapy in NSCLC. Mechanically, RNA-seq results showed that ANKRD29 could regulate MAPK signaling pathway. Moreover, we screened two potential agonists for ANKRD29.

Conclusions
ANKRD29 functions as a new tumor suppressor in NSCLC tumorigenesis and could be developed as a biomarker for prognostic prediction, immunotherapy response, and drug susceptibility evaluation of NSCLC in the future.
A phase IIb, open-label, randomized controlled dose ranging multi-centre trial to evaluate the safety, tolerability, pharmacokinetics and exposure-response relationship of different doses of delpazolid in combination with bedaquiline delamanid moxifloxacin in adult subjects with newly diagnosed, uncomplicated, smear-positive, drug-sensitive pulmonary tuberculosis
Authors: Dierig A , Hoelscher M , Schultz S , Hoffmann L , Jarchow-MacDonald A , Svensson EM , Te Brake L , Aarnoutse R , Boeree M , McHugh TD , Wildner LM , Gong X , Phillips PPJ , Minja LT , Ntinginya N , Mpagama S , Liyoyo A , Wallis RS , Sebe M , Mhimbira FA , Mbeya B , Rassool M , Geiter L , Cho YL , Heinrich N 
Published: June 2023

Abstract
Background
Linezolid is an effective, but toxic anti-tuberculosis drug that is currently recommended for the treatment of drug-resistant tuberculosis. Improved oxazolidinones should have a better safety profile, while preserving efficacy. Delpazolid is a novel oxazolidinone developed by LegoChem Biosciences Inc. that has been evaluated up to phase 2a clinical trials. Since oxazolidinone toxicity can occur late in treatment, LegoChem Biosciences Inc. and the PanACEA Consortium designed DECODE to be an innovative dose-ranging study with long-term follow-up for determining the exposure–response and exposure–toxicity relationship of delpazolid to support dose selection for later studies. Delpazolid is administered in combination with bedaquiline, delamanid and moxifloxacin.

Methods
Seventy-five participants with drug-sensitive, pulmonary tuberculosis will receive bedaquiline, delamanid and moxifloxacin, and will be randomized to delpazolid dosages of 0 mg, 400 mg, 800 mg, 1200 mg once daily, or 800 mg twice daily, for 16 weeks. The primary efficacy endpoint will be the rate of decline of bacterial load on treatment, measured by MGIT liquid culture time to detection from weekly sputum cultures. The primary safety endpoint will be the proportion of oxazolidinone class toxicities; neuropathy, myelosuppression, or tyramine pressor response.

Participants who convert to negative liquid media culture by week 8 will stop treatment after the end of their 16-week course and will be observed for relapse until week 52. Participants who do not convert to negative culture will receive continuation phase treatment with rifampicin and isoniazid to complete a six-month treatment course.

Discussion
DECODE is an innovative dose-finding trial, designed to support exposure-response modelling for safe and effective dose selection. The trial design allows assessment of occurrence of late toxicities as observed with linezolid, which is necessary in clinical evaluation of novel oxazolidinones. The primary efficacy endpoint is the change in bacterial load, an endpoint conventionally used in shorter dose-finding trials. Long-term follow-up after shortened treatment is possible through a safety rule excluding slow-and non-responders from potentially poorly performing dosages.

Trial registration
DECODE was registered in ClinicalTrials.gov before recruitment start on 22 October 2021 (NCT04550832).
More efficient and inclusive time-to-event trials with covariate adjustment: a simulation study
Authors: Momal Raphaëlle , Li Honghao , Trichelair Paul , Blum Michael G. B. , Balazard Félix 
Published: June 2023

AbstractAdjustment for prognostic covariates increases the statistical power of randomized trials. The factors influencing the increase of power are well-known for trials with continuous outcomes. Here, we study which factors influence power and sample size requirements in time-to-event trials. We consider both parametric simulations and simulations derived from the Cancer Genome Atlas (TCGA) cohort of hepatocellular carcinoma (HCC) patients to assess how sample size requirements are reduced with covariate adjustment. Simulations demonstrate that the benefit of covariate adjustment increases with the prognostic performance of the adjustment covariate (C-index) and with the cumulative incidence of the event in the trial. For a covariate that has an intermediate prognostic performance (C-index=0.65), the reduction of sample size varies from 3.1% when cumulative incidence is of 10% to 29.1% when the cumulative incidence is of 90%. Broadening eligibility criteria usually reduces statistical power while our simulations show that it can be maintained with adequate covariate adjustment. In a simulation of adjuvant trials in HCC, we find that the number of patients screened for eligibility can be divided by 2.4 when broadening eligibility criteria. Last, we find that the Cox-Snell $${R}_{\mathsf{C}\mathsf{S}}^{2}$$

R

C
S

2

is a conservative estimation of the reduction in sample size requirements provided by covariate adjustment. Overall, more systematic adjustment for prognostic covariates leads to more efficient and inclusive clinical trials especially when cumulative incidence is large as in metastatic and advanced cancers. Code and results are available at https://github.com/owkin/CovadjustSim.
End-ischemic hypothermic oxygenated perfusion for extended criteria donors in liver transplantation: a multicenter, randomized controlled trial—HOPExt
Authors: Pradat Pierre , Pantel Solene , Maynard Marianne , Lalande Laure , Thevenon Sylvie , Adam Rene , Allard Marc-Antoine , Robin Fabien , Rayar Michel , Boleslawski Emmanuel , Scatton Olivier , Chirica Mircea , Faitot François , Bachellier Philippe , Soubrane Olivier , Mohkam Kayvan , Mabrut Jean-Yves , Lesurtel Mickaël 
Published: June 2023

Abstract

Background
Given the scarce donor supply, an increasing number of so-called marginal or extended criteria donor (ECD) organs are used for liver transplantation. These ECD liver grafts are however known to be associated with a higher rate of early allograft dysfunction and primary non-function because of a greater vulnerability to ischemia–reperfusion injury. The end-ischemic hypothermic oxygenated machine perfusion (HOPE) technique may improve outcomes of liver transplantation with ECD grafts by decreasing reperfusion injury.

Methods
HOPExt trial is a comparative open-label, multicenter, national, prospective, randomized, controlled study, in two parallel groups, using static cold storage, the gold standard procedure, as control. The trial will enroll adult patients on the transplant waiting list for liver failure or liver cirrhosis and/or liver malignancy requiring liver transplantation and receiving an ECD liver graft from a brain-dead donor. In the experimental group, ECD liver grafts will first undergo a classical static cold (4 °C) storage followed by a hypothermic oxygenated perfusion (HOPE) for a period of 1 to 4 h. The control group will consist of the classic static cold storage which is the gold standard procedure in liver transplantation. The primary objective of this trial is to study the efficacy of HOPE used before transplantation of ECD liver grafts from brain-dead donors in reducing postoperative early allograft dysfunction within the first 7 postoperative days compared to simple cold static storage.

Discussion
We present in this protocol all study procedures in regard to the achievement of the HOPExt trial, to prevent biased analysis of trial outcomes and improve the transparency of the trial results. Enrollment of patients in the HOPExt trial has started on September 10, 2019, and is ongoing.

Trial registration
ClinicalTrials.gov NCT03929523. Registered on April 29, 2019, before the start of inclusion.
MicroRNA-29a-3p prevents Schistosoma japonicum-induced liver fibrosis by targeting Roundabout homolog 1 in hepatic stellate cells
Authors: Kong Hongyan , Song Qiqin , Hu Wenjiang , Guo Shusen , Xiang Dandan , Huang Shuaiwen , Xu Xin , He Jinan , Pan Lanyue , Tao Ran , Yu Haijing , Huang Jiaquan 
Published: June 2023

Abstract
Background
Schistosomiasis is a serious but neglected parasitic disease in humans that may lead to liver fibrosis and death. Activated hepatic stellate cells (HSCs) are the principal effectors that promote the accumulation of extracellular matrix (ECM) proteins during hepatic fibrosis. Aberrant microRNA-29 expression is involved in the development of fibrotic diseases. However, less is known about the role of miR-29 in Schistosoma japonicum (S. japonicum)-induced hepatic fibrosis.

Methods
The levels of microRNA-29a-3p (miR-29a-3p) and Roundabout homolog 1 (Robo1) were examined in liver tissues during S. japonicum infection. The possible involvement of the miR-29a-3p-Robo1 signaling pathway was determined. We used MIR29A conditional knock-in mice and mice injected with an miR-29a-3p agomir to investigate the role of miR-29a-3p in schistosomiasis-induced hepatic fibrosis. The functional contributions of miR-29a-3p-Robo1 signaling in liver fibrosis and HSC activation were investigated using primary mouse HSCs and the human HSC cell line LX-2.

Results
MiR-29a-3p was downregulated in humans and mice with schistosome-induced fibrosis, and Robo1 was upregulated in liver tissues. The miR-29a-3p targeted Robo1 and negatively regulated its expression. Additionally, the expression level of miR-29a-3p in schistosomiasis patients was highly correlated with the portal vein and spleen thickness diameter, which represent the severity of fibrosis. Furthermore, we demonstrated that efficient and sustained elevation of miR-29a-3p reversed schistosome-induced hepatic fibrosis. Notably, we showed that miR-29a-3p targeted Robo1 in HSCs to prevent the activation of HSCs during infection.

Conclusions
Our results provide experimental and clinical evidence that the miR-29a-3p-Robo1 signaling pathway in HSCs plays an important role in the development of hepatic fibrosis. Therefore, our study highlights the potential of miR-29a-3p as a therapeutic intervention for schistosomiasis and other fibrotic diseases.

Graphical Abstract
Imaging features of the postoperative spine: a guide to basic understanding of spine surgical procedures
Authors: Girão Marília Maria Vasconcelos , Miyahara Lucas Kenzo , Dwan Viviane Sayuri Yamachira , Baptista Eduardo , Taneja Atul Kumar , Gotfryd Alberto , do Amaral e Castro Adham 
Published: June 2023

Abstract
Spinal surgical procedures are becoming more common over the years, and imaging studies can be requested in the postoperative setting, such as a baseline study when implants are used, or when there is a new postoperative issue reported by the patient or even as routine surveillance. Therefore, it helps the surgeon in the appropriate management of cases. In this context, there is increasing importance of the radiologist in the adequate interpretation of postoperative images, as well as in the choice of the most appropriate modality for each case, especially among radiographs, computed tomography, magnetic resonance imaging and nuclear medicine. It is essential to be familiar with the main types of surgical techniques and imaging characteristics of each one, including the type and correct positioning of hardware involved, to differentiate normal and abnormal postoperative appearances. The purpose of this pictorial essay is to illustrate and discuss the more frequently used spine surgical interventions and their imaging characteristics, with an emphasis on classical decompression and fusion/stabilization procedures.

Graphical Abstract

Key points

Plain radiographs remain the main modality for baseline, dynamic evaluation, and follow-ups.

CT is the method of choice for assessing bone fusion, hardware integrity and loosening.

MRI should be used to evaluate bone marrow and soft tissue complications.

Radiologists should be familiar with most performed spinal procedures in order to differentiate normal and abnormal.

Critical relevance statement
This article discusses the main surgical procedures involved in the spine, which can be didactically divided into decompression, stabilization-fusion, and miscellaneous, as well as the role of diagnostic imaging methods and their main findings in this context.
New data on the marine Upper Triassic palaeobiota from the Polzberg Konservat-Lagerstätte in Austria
Authors: Lukeneder Alexander , Lukeneder Petra 
Published: June 2023

AbstractHere we report new data on the Upper Triassic Polzberg Konservat-Lagerstätte in the Northern Calcarous Alps of Lower Austria. We examined new fossil material obtained from bed-by-bed collections of the well-laminated Reingraben Shales. Over 5290 new fossils of various marine taxa were collected within the fossiliferous layers from the Early Carnian (Julian 2 Ib, Austrotrachyceras austriacum Zone). The newly collected assemblage comprises ammonoids (Austrotrachyceras, Paratrachyceras, Carnites, Simonyceras), belemnoids (Phragmoteuthis, Lunzoteuthis), bivalves (Halobia, div. indet taxa), gastropods (caenogastropods/heterobranchs), thylacocephalan arthropods (Austriocaris, Atropicaris), crustaceans (the decapod Platychela and isopods Obtusotelson, Discosalaputium), branchiopods (Euestheria), polychaetes (Palaeoaphrodite sp. and an unidentified eunicid polychaete), acytinopterygians (Saurichthys, Polzbergia, Peltopleurus, Habroichthys), cartilaginous fishes (Acrodus), coelacanth fish (“Coelacanthus”), a lungfish (Tellerodus), and numerous conodont clusters (Mosherella). Bromalites (coprolites and regurgitalites) produced by piscivorous actinopterygians and durophagous fish accompany the Polzberg palaeobiota along with rare plant remains (Voltzia, div. indet plants). Based on new findings the palaeobiota characterises an intermittent colonisation by abundant benthic halobiid bivalves and a predator-dominated (fish, belemnoids) nektic community. The prerequisites for high-quality preservation—calm and oxygen-depleted conditions—prevailed at the sea floor of the Polzberg Konservat-Lagerstätte. Normal marine conditions prevail in the Reifling Basin, occasionally interrupted by freshwater influx. New in situ findings of benthic and nektic taxa highlight the great value of the unique Polzberg palaeobiota and the autochthonous deposition of the inhabitants within the palaeohabitat. The fauna and flora from the Polzberg Konservat-Lagerstätte, deposited during the Carnian Pluvial Episode or Carnian Wet Intermezzo, points to a carbonate platform decline followed by the deposition of laminated deposits in warmer and wetter conditions.
Optimal distribution-free concentration for the log-likelihood function of Bernoulli variables
Authors: Ren Zhonggui 
Published: June 2023

AbstractThis paper aims to establish distribution-free concentration inequalities for the log-likelihood function of Bernoulli variables, which means that the tail bounds are independent of the parameters. Moreover, Bernstein’s and Bennett’s inequalities with optimal constants are obtained. The simulation study shows significant improvements over the previous results.
EIF4A3-induced Circ_0001187 facilitates AML suppression through promoting ubiquitin-proteasomal degradation of METTL3 and decreasing m6A modification level mediated by miR-499a-5p/RNF113A pathway
Authors: Yang Xinyu , Han Fengjiao , Hu Xiang , Li Guosheng , Wu Hanyang , Can Can , Wei Yihong , Liu Jinting , Wang Ruiqing , Jia Wenbo , ji Chunyan , Ma Daoxin 
Published: June 2023

AbstractAberrant expression of circRNAs has been proven to play a crucial role in the progression of acute myeloid leukemia (AML); however, its regulatory mechanism remains unclear. Herein, we identified a novel circRNA, Circ_0001187, which is downregulated in AML patients, and its low level contributes to a poor prognosis. We further validated their expression in large-scale samples and found that only the expression of Circ_0001187 was significantly decreased in newly diagnosed (ND) AML patients and increased in patients with hematological complete remission (HCR) compared with controls. Knockdown of Circ_0001187 significantly promoted proliferation and inhibited apoptosis of AML cells in vitro and in vivo, whereas overexpression of Circ _0001187 exerted the opposite effects. Interestingly, we found that Circ_0001187 decreases mRNA m6A modification in AML cells by enhancing METTL3 protein degradation. Mechanistically, Circ_0001187 sponges miR-499a-5p to enhance the expression of E3 ubiquitin ligase RNF113A, which mediates METTL3 ubiquitin/proteasome-dependent degradation via K48-linked polyubiquitin chains. Moreover, we found that the low expression of Circ _0001187 is regulated by promoter DNA methylation and histone acetylation. Collectively, our findings highlight the potential clinical implications of Circ _0001187 as a key tumor suppressor in AML via the miR-499a-5p/RNF113A/METTL3 pathway.
Oncofetal protein IGF2BPs in human cancer: functions, mechanisms and therapeutic potential
Authors: Zhu Tian-Yu , Hong Lian-Lian , Ling Zhi-Qiang 
Published: June 2023

AbstractN6-methyladenosine (m6A) is the most prevalent and well-characterized internal chemical modification in eukaryotic RNA, influencing gene expression and phenotypic changes by controlling RNA fate. Insulin-like growth factor-2 mRNA-binding proteins (IGF2BPs) preferentially function as m6A effector proteins, promoting stability and translation of m6A-modified RNAs. IGF2BPs, particularly IGF2BP1 and IGF2BP3, are widely recognized as oncofetal proteins predominantly expressed in cancer rather than normal tissues, playing a critical role in tumor initiation and progression. Consequently, IGF2BPs hold potential for clinical applications and serve as a good choice for targeted treatment strategies. In this review, we discuss the functions and mechanisms of IGF2BPs as m6A readers and explore the therapeutic potential of targeting IGF2BPs in human cancer.
Divergent migration routes reveal contrasting energy-minimization strategies to deal with differing resource predictability
Authors: Shuert Courtney R. , Hussey Nigel E. , Marcoux Marianne , Heide-Jørgensen Mads Peter , Dietz Rune , Auger-Méthé Marie 
Published: June 2023

AbstractBackgroundSeasonal long-distance movements are a common feature in many taxa allowing animals to deal with seasonal habitats and life-history demands. Many species use different strategies to prioritize time- or energy-minimization, sometimes employing stop-over behaviours to offset the physiological burden of the directed movement associated with migratory behaviour. Migratory strategies are often limited by life-history and environmental constraints, but can also be modulated by the predictability of resources en route. While theory on population-wide strategies (e.g. energy-minimization) are well studied, there are increasing evidence for individual-level variation in movement patterns indicative of finer scale differences in migration strategies.MethodsWe aimed to explore sources of individual variation in migration strategies for long-distance migrators using satellite telemetry location data from 41 narwhal spanning a 21-year period. Specifically, we aimed to determine and define the long-distance movement strategies adopted and how environmental variables may modulate these movements. Fine-scale movement behaviours were characterized using move-persistence models, where changes in move-persistence, highlighting autocorrelation in a movement trajectory, were evaluated against potential modulating environmental covariates. Areas of low move-persistence, indicative of area-restricted search-type behaviours, were deemed to indicate evidence of stop-overs along the migratory route.ResultsHere, we demonstrate two divergent migratory tactics to maintain a similar overall energy-minimization strategy within a single population of narwhal. Narwhal migrating offshore exhibited more tortuous movement trajectories overall with no evidence of spatially-consistent stop-over locations across individuals. Nearshore migrating narwhal undertook more directed routes, contrasted by spatially-explicit stop-over behaviour in highly-productive fjord and canyon systems along the coast of Baffin Island for periods of several days to several weeks.ConclusionsWithin a single population, divergent migratory tactics can achieve a similar overall energy-minimizing strategy within a species as a response to differing trade-offs between predictable and unpredictable resources. Our methodological approach, which revealed the modulators of fine-scale migratory movements and predicted regional stop-over sites, is widely applicable to a variety of other aquatic and terrestrial species. Quantifying marine migration strategies will be key for adaptive conservation in the face of climate change and ever increasing human pressures.