bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tumor-suppressive MEG3 induces microRNA-493-5p expression to reduce arabinocytosine chemoresistance of acute myeloid leukemia cells by downregulating the METTL3/MYC axis
Authors: Wang Airong , Chen Yufei , Shi Luyao , Li Mengya , Li Lingling , Wang Shujuan , Wang Chong 
Published: June 2022

Abstract
Background
Chemoresistance serves as a huge obstacle for acute myeloid leukemia (AML) patients. To counteract the chemoresistance in AML cells, we discussed the role of maternally expressed gene 3 (MEG3) in arabinocytosine (AraC) chemoresistance in AML cells.

Methods
MEG3, microRNA (miR)-493-5p, methyltransferase-like 3 (METTL3) and MYC expression in AML cells was determined and then their interactions were also analyzed. Then, the viability and apoptosis of AML cells were determined through loss- and gain- function assay. The level of m6A modification in AML cells was examined. AML mouse models were also established to validate the potential roles of MEG3.

Results
MEG3 and miR-493-5p were downregulated in AML cells, and they were lower in resistant cells than in parental cells. MEG3 led to elevated expression of miR-493-5p which targeted METTL3. METTL3 increased expression of MYC by promoting its m6A levels. Overexpression of MEG3 and miR-493-5p or knockdown of METTL3 inhibited HL-60 and Molm13 cell proliferation and promoted their apoptosis. Overexpressed MEG3 induced heightened sensitivity of AML cells to AraC. However, the suppression of miR-493-5p reversed the effects of overexpressed MEG3 on AML cells.

Conclusions
Collectively, MEG3 could upregulate miR-493-5p expression and suppress the METTL3/MYC axis through MYC m6A methylation, by which MEG3 promoted the chemosensitivity of AML cells.
Inhibition of autophagy by chloroquine prevents resistance to PI3K/AKT inhibitors and potentiates their antitumor effect in combination with paclitaxel in triple negative breast cancer models
Authors: Cocco Stefania , Leone Alessandra , Roca Maria Serena , Lombardi Rita , Piezzo Michela , Caputo Roberta , Ciardiello Chiara , Costantini Susan , Bruzzese Francesca , Sisalli Maria José , Budillon Alfredo , De Laurentiis Michelino 
Published: June 2022

Abstract
Background
Triple negative breast cancer (TNBC) is an aggressive disease characterized by high risk of relapse and development of resistance to different chemotherapy agents. Several targeted therapies have been investigated in TNBC with modest results in clinical trials. Among these, PI3K/AKT inhibitors have been evaluated in addition to standard therapies, yielding conflicting results and making attempts on elucidating inherent mechanisms of resistance of great interest. Increasing evidences suggest that PI3K/AKT inhibitors can induce autophagy in different cancers. Autophagy represents a supposed mechanism of drug-resistance in aggressive tumors, like TNBC. We, therefore, investigated if two PI3K/AKT inhibitors, ipatasertib and taselisib, could induce autophagy in breast cancer models, and whether chloroquine (CQ), a well known autophagy inhibitor, could potentiate ipatasertib and taselisib anti-cancer effect in combination with conventional chemotherapy.

Methods
The induction of autophagy after ipatasertib and taselisib treatment was evaluated in MDAMB231, MDAM468, MCF7, SKBR3 and MDAB361 breast cancer cell lines by assaying LC3-I conversion to LC3-II through immunoblotting and immunofluorescence. Other autophagy-markers as p62/SQSTM1 and ATG5 were evaluated by immunoblotting. Synergistic antiproliferative effect of double and triple combinations of ipatasertib/taselisib plus CQ and/or paclitaxel were evaluated by SRB assay and clonogenic assay. Anti-apoptotic effect of double combination of ipatasertib/taselisib plus CQ was evaluated by increased cleaved-PARP by immunoblot and by Annexin V- flow cytometric analysis. In vivo experiments were performed on xenograft model of MDAMB231 in NOD/SCID mice.

Results
Our results suggested that ipatasertib and taselisib induce increased autophagy signaling in different breast cancer models. This effect was particularly evident in PI3K/AKT resistant TNBC cells, where the inhibition of autophagy by CQ potentiates the therapeutic effect of PI3K/AKT inhibitors in vitro and in vivo TNBC models, synergizing with taxane-based chemotherapy.

Conclusion
These data suggest that inhibition of authophagy with CQ could overcome mechanism of drug resistance to PI3K/AKT inhibitors plus paclitaxel in TNBC making the evaluation of such combinations in clinical trials warranted.
MHBSt167 induced autophagy promote cell proliferation and EMT by activating the immune response in L02 cells
Authors: Cheng Bin , Wang Qiong , Wei Zhiqiang , He Yulin , Li Ruiming , Liu Guohua , Zeng Shaobo , Meng Zhongji 
Published: June 2022

Abstract
Background
Hepatitis B virus can induce hepatocellular carcinoma (HCC) by inducing a host immune response against infected hepatocytes. C-terminally truncated middle surface protein (MHBSt) has been reported to contribute to HCC through transcriptional activation in epidemiology studies, while the underlying mechanism of MHBSt-induced HCC is unknown.

Methods
In this study, a premature stop at codon 167 in MHBS (MHBSt167) was investigated into eukaryotic expression plasmid pcDNA3.1(-). MHBSt167 expressed plasmid was transfected into the L02 cell line, cell proliferation was analyzed by CCK-8 and high-content screening assays, the cell cycle was analyzed by flow cytometry, and epithelial-to-mesenchymal transition and autophagy were analyzed by immunoblotting and immunofluorescence. NF-κB activation and the MHBSt167-induced immune response were analyzed by immunoblotting and immunofluorescence. IFN-α, IFN-β and IL-1α expression were analyzed by qPCR. Autophagy inhibitors were used to analyze the relationship between the immune response and autophagy.

Results
The results showed that MHBSt167 promoted L02 cell proliferation, accelerated cell cycle progression from the S to G2 phase and promoted epithelial-to-mesenchymal transition through ER-stress, leading to autophagy and NF-κB activation and increased immune-related factor expression. The MHBSt167-induced acceleration of cell proliferation and the cell cycle was abolished by autophagy or NF-κB inhibitors.

Conclusion
In summary, MHBSt167 could promote cell proliferation, accelerate cell cycle progression, induce EMT and activate autophagy through ER-stress to induce the host immune response, supporting a potential role of MHBSt167 in contributing to carcinogenesis.
Assessing organ at risk position variation and its impact on delivered dose in kidney SABR
Authors: Gaudreault Mathieu , Siva Shankar , Kron Tomas , Hardcastle Nicholas 
Published: June 2022

Abstract
Background
Delivered organs at risk (OARs) dose may vary from planned dose due to interfraction and intrafraction motion during kidney SABR treatment. Cases of bowel stricture requiring surgery post SABR treatment were reported in our institution. This study aims to provide strategies to reduce dose deposited to OARs during SABR treatment and mitigate risk of gastrointestinal toxicity.

Methods
Small bowel (SB), large bowel (LB) and stomach (STO) were delineated on the last cone beam CT (CBCT) acquired before any dose had been delivered (PRE CBCT) and on the first CBCT acquired after any dose had been delivered (MID CBCT). OAR interfraction and intrafraction motion were estimated from the shortest distance between OAR and the internal target volume (ITV). Adaptive radiation therapy (ART) was used if dose limits were exceeded by projecting the planned dose on the anatomy of the day.

Results
In 36 patients, OARs were segmented on 76 PRE CBCTs and 30 MID CBCTs. Interfraction motion was larger than intrafraction motion in STO (p-value = 0.04) but was similar in SB (p-value = 0.8) and LB (p-value = 0.2). LB was inside the planned 100% isodose in all PRE CBCTs and MID CBCTs in the three patients that suffered from bowel stricture. SB D0.03cc was exceeded in 8 fractions (4 patients). LB D1.5cc was exceeded in 4 fractions (2 patients). Doses to OARs were lowered and limits were all met with ART on the anatomy of the day.

Conclusions
Interfraction motion was responsible for OARs overdosage. Dose limits were respected by using ART with the anatomy of the day.
Australasian Malignant PLeural Effusion (AMPLE)-3 trial: study protocol for a multi-centre randomised study comparing indwelling pleural catheter (±talc pleurodesis) versus video-assisted thoracoscopic surgery for management of malignant pleural effusion
Authors: Fitzgerald Deirdre B. , Sidhu Calvin , Budgeon Charley , Tan Ai Ling , Read Catherine A. , Kwan Benjamin C. H. , Smith Nicola Ann , Fysh Edward T. , Muruganandan Sanjeevan , Saghaie Tajalli , Shrestha Ranjan , Badiei Arash , Nguyen Phan , Burke Andrew , Goddard John , Windsor Morgan , McDonald Julie , Wright Gavin , Czarnecka Kasia , Sivakumar Parthipan , Yasufuku Kazuhiro , Feller-Kopman David J. , Maskell Nick A. , Murray Kevin , Lee Y. C. Gary 
Published: June 2022

Abstract
Introduction
Malignant pleural effusions (MPEs) are common. MPE causes significant breathlessness and impairs quality of life. Indwelling pleural catheters (IPC) allow ambulatory drainage and reduce hospital days and re-intervention rates when compared to standard talc slurry pleurodesis. Daily drainage accelerates pleurodesis, and talc instillation via the IPC has been proven feasible and safe. Surgical pleurodesis via video-assisted thoracoscopic surgery (VATS) is considered a one-off intervention for MPE and is often recommended to patients who are fit for surgery. The AMPLE-3 trial is the first randomised trial to compare IPC (±talc pleurodesis) and VATS pleurodesis in those who are fit for surgery.

Methods and analysis
A multi-centre, open-labelled randomised trial of patients with symptomatic MPE, expected survival of ≥ 6 months and good performance status randomised 1:1 to either IPC or VATS pleurodesis. Participant randomisation will be minimised for (i) cancer type (mesothelioma vs non-mesothelioma); (ii) previous pleurodesis (vs not); and (iii) trapped lung, if known (vs not). Primary outcome is the need for further ipsilateral pleural interventions over 12 months or until death, if sooner. Secondary outcomes include days in hospital, quality of life (QoL) measures, physical activity levels, safety profile, health economics, adverse events, and survival. The trial will recruit 158 participants who will be followed up for 12 months.

Ethics and dissemination
Sir Charles Gairdner and Osborne Park Health Care Group (HREC) has approved the study (reference: RGS356). Results will be published in peer-reviewed journals and presented at scientific meetings.

Discussion
Both IPC and VATS are commonly used procedures for MPE. The AMPLE-3 trial will provide data to help define the merits and shortcomings of these procedures and inform future clinical care algorithms.

Trial registration
Australia New Zealand Clinical Trial Registry ACTRN12618001013257. Registered on 18 June 2018.
Protocol version: Version 3.00/4.02.19
Diagnosis of animal trypanosomoses: proper use of current tools and future prospects
Authors: Desquesnes Marc , Sazmand Alireza , Gonzatti Marisa , Boulangé Alain , Bossard Géraldine , Thévenon Sophie , Gimonneau Geoffrey , Truc Philippe , Herder Stéphane , Ravel Sophie , Sereno Denis , Waleckx Etienne , Jamonneau Vincent , Jacquiet Philippe , Jittapalapong Sathaporn , Berthier David , Solano Philippe , Hébert Laurent 
Published: June 2022

AbstractReliable diagnostic tools are needed to choose the appropriate treatment and proper control measures for animal trypanosomoses, some of which are pathogenic.Trypanosoma cruzi, for example, is responsible for Chagas disease in Latin America. Similarly, pathogenic animal trypanosomoses of African origin (ATAO), including a variety ofTrypanosomaspecies and subspecies, are currently found in Africa, Latin America and Asia. ATAO limit global livestock productivity and impact food security and the welfare of domestic animals. This review focusses on implementing previously reviewed diagnostic methods, in a complex epizootiological scenario, by critically assessing diagnostic results at the individual or herd level. In most cases, a single diagnostic method applied at a given time does not unequivocally identify the various parasitological and disease statuses of a host. These include “non-infected”, “asymptomatic carrier”, “sick infected”, “cured/not cured” and/or “multi-infected”. The diversity of hosts affected by these animal trypanosomoses and their vectors (or other routes of transmission) is such that integrative, diachronic approaches are needed that combine: (i) parasite detection, (ii) DNA, RNA or antigen detection and (iii) antibody detection, along with epizootiological information. The specificity of antibody detection tests is restricted to the genus or subgenus due to cross-reactivity with otherTrypanosomaspp. and Trypanosomatidae, but sensitivity is high. The DNA-based methods implemented over the last three decades have yielded higher specificity and sensitivity for active infection detection in hosts and vectors. However, no single diagnostic method can detect all active infections and/or trypanosome species or subspecies. The proposed integrative approach will improve the prevention, surveillance and monitoring of animal trypanosomoses with the available diagnostic tools. However, further developments are required to address specific gaps in diagnostic methods and the sustainable control or elimination of these diseases.Graphical Abstract
An introduction to spatial transcriptomics for biomedical research
Authors: Williams Cameron G. , Lee Hyun Jae , Asatsuma Takahiro , Vento-Tormo Roser , Haque Ashraful 
Published: June 2022

AbstractSingle-cell transcriptomics (scRNA-seq) has become essential for biomedical research over the past decade, particularly in developmental biology, cancer, immunology, and neuroscience. Most commercially available scRNA-seq protocols require cells to be recovered intact and viable from tissue. This has precluded many cell types from study and largely destroys the spatial context that could otherwise inform analyses of cell identity and function. An increasing number of commercially available platforms now facilitate spatially resolved, high-dimensional assessment of gene transcription, known as ‘spatial transcriptomics’. Here, we introduce different classes of method, which either record the locations of hybridized mRNA molecules in tissue, image the positions of cells themselves prior to assessment, or employ spatial arrays of mRNA probes of pre-determined location. We review sizes of tissue area that can be assessed, their spatial resolution, and the number and types of genes that can be profiled. We discuss if tissue preservation influences choice of platform, and provide guidance on whether specific platforms may be better suited to discovery screens or hypothesis testing. Finally, we introduce bioinformatic methods for analysing spatial transcriptomic data, including pre-processing, integration with existing scRNA-seq data, and inference of cell-cell interactions. Spatial -omics methods are already improving our understanding of human tissues in research, diagnostic, and therapeutic settings. To build upon these recent advancements, we provide entry-level guidance for those seeking to employ spatial transcriptomics in their own biomedical research.
Clinical experience and treatment strategy of leiomyosarcoma originating from the renal vein
Authors: Baheen Qais , Bi Hai , Wang Kai , Lu Min , Zhang Hongxian , Ma Lulin 
Published: June 2022

Abstract
Background
Leiomyosarcoma originating from the renal vein (RVLMS) is extremely rare. RVLMS lacks specific clinical manifestations and specific imaging features. This article discusses the epidemiological characteristics and diagnostic difficulties of RVLMS, as well as imaging features, differential diagnosis, treatment strategy, and prognostic factors of this disease.

Method
A case of RVLMS at our center, and 55 cases from the literature based on the PubMed search.

Results
Total operation time was 224 min, and total blood loss during the surgery was 200 ml. Resected tumor was irregular in shape, with negative margins. On the 6th day after the operation, the drainage tube was removed, and the patient was discharged from the hospital. Postoperative pathological results confirmed the renal vein leiomyosarcoma: spindle cell sarcoma, diffuse severe atypia, S-100 (-), SMA ( +), desmin ( +), CD34 (−), CD99 ( +). Twenty-seven months after the surgery, the patient is alive, and without local recurrence or distant metastases.

Conclusion
Unspecific clinical manifestations and imaging features make the diagnosis of RVLMS difficult. Most patients are diagnosed intra-operatively or following postoperative pathology. Differential diagnosis with paraganglioma (PG) and retroperitoneal sarcoma (RPS) should be made. Early and complete resection is considered as the first choice of treatment, and whether to preserve the kidney is based on the patient's condition. RVLMS is highly malignant, and may recur locally or metastasize to distant locations; therefore, adjuvant therapy and regular follow-up should be carried out after surgery.
Unravelling the construction of silver filigree spheres from a seventeenth century shipwreck using non-invasive imaging
Authors: van der Stok-Nienhuis Janneke , Beentjes Tonny , Ngan-Tillard Dominique , van Eijck Lambert , Joosten Ineke , van Bommel Maarten R. 
Published: June 2022

Abstract
The structure of five rare filigree spheres from a seventeenth century shipwreck was examined in order to unravel their condition, manufacturing process and function. This study focuses on the application of non-invasive imaging techniques: optical microscopy, X-radiography, X-ray micro-computed tomography and neutron computed tomography. A valuation of different aspects of the applied techniques was made, aiding stakeholders in decision-making on research and conservation. The combination of theory and scientific information was used to obtain an improved understanding of the manufacturing process and function of the filigree spheres.
A novel second-stage surgical strategy for severely obese patient with pancreatic neuroendocrine tumor: a case report
Authors: Umemura Akira , Sasaki Akira , Nitta Hiroyuki , Katagiri Hirokatsu , Kanno Shoji , Takeda Daiki , Ando Taro , Amano Satoshi , Nishiya Masao , Uesugi Noriyuki , Sugai Tamotsu 
Published: June 2022

Abstract
Background
Severely obese patients can have other diseases requiring surgical treatment. In such patients, bariatric surgeries are considered a precursor to operations targeting the original disease for the purpose of reducing severe perioperative complications. Pancreatic ectopic fat deposition increases pancreas volume (PV) and thickness, which can worsen insulin resistance and islet β cell function. To address this problem, we present a novel two-stage surgical strategy performed on a severely obese patient with pancreatic neuroendocrine tumor (PNET) consisting of laparoscopic sleeve gastrectomy (LSG) as a metabolic surgery followed by laparoscopic spleen-preserving distal pancreatectomy (LSPDP).

Case presentation
A 56-year-old man was referred to our hospital for further investigation of a pancreatic tumor. His initial body weight and body mass index (BMI) were 94.0 kg and 37.2 kg/m2, respectively. Contrast computed tomography revealed an enhanced tumor measuring 15 mm on the pancreatic body. The pancreas thickness and PV were 32 mm and 148 mL, respectively. An endoscopic ultrasonographic fine needle aspiration identified the tumor as PNET-G1. We first performed LSG, the patient’s body weight and BMI had decreased dramatically to 64.0 kg and 25.3 kg/m2 at 6 months after LSG. The pancreas thickness and PV had also decreased to 17 mm and 99 mL, respectively, with no tumor growth. Since LSG has been shown to reduce the perioperative risk factors of LSPDP, and to improve insulin resistance and recovery of islet β cell function, we performed LSPDP for PNET-G1 as a second-stage surgery. The postoperative course was unremarkable, and the patient was discharged on postoperative day 14 without symptomatic postoperative pancreatic fistula (POPF). He was followed without recurrence or type 2 diabetes (T2D) onset for 6 months after LSPDP.

Conclusions
We present a novel two-stage surgical strategy for a severely obese patient with PNET, consisting of LSG as a metabolic surgery for severe obesity, followed by LSPDP after confirmation of good weight loss and metabolic effects. LSG before pancreatectomy may have a potential to reduce pancreas thickness and recovery of islet β cell function in severely obese patients, thereby reducing the risk of clinically relevant POPF and post-pancreatectomy T2D onset.
A Proposed Framework to Describe Movement Variability within Sporting Tasks: A Scoping Review
Authors: Cowin Jake , Nimphius Sophia , Fell James , Culhane Peter , Schmidt Matthew 
Published: June 2022

AbstractMovement variability is defined as the normal variations in motor performance across multiple repetitions of a task. However, the term “movement variability” can mean different things depending on context, and when used by itself does not capture the specifics of what has been investigated. Within sport, complex movements are performed repeatedly under a variety of different constraints (e.g. different situations, presence of defenders, time pressure). Movement variability has implications for sport performance and injury risk management. Given the importance of movement variability, it is important to understand the terms used to measure and describe it. This broad term of “movement variability” does not specify the different types of movement variability that are currently being assessed in the sporting literature. We conducted a scoping review (1) to assess the current terms and definitions used to describe movement variability within sporting tasks and (2) to utilise the results of the review for a proposed framework that distinguishes and defines the different types of movement variability within sporting tasks. To be considered eligible, sources must have assessed a sporting movement or skill and had at least one quantifiable measure of movement variability. A total of 43 peer-reviewed journal article sources were included in the scoping review. A total of 280 terms relating to movement variability terminology were extracted using a data-charting form jointly developed by two reviewers. One source out of 43 (2%) supplied definitions for all types of movement variability discussed. Moreover, 169 of 280 terms (60%) were undefined in the source material. Our proposed theoretical framework explains three types of movement variability: strategic, execution, and outcome. Strategic variability describes the different approaches or methods of movement used to complete a task. Execution variability describes the intentional and unintentional adjustments of the body between repetitions within the same strategy. Outcome variability describes the differences in the result or product of a movement. These types emerged from broader frameworks in motor control and were adapted to fit the movement variability needs in sports literature. By providing specific terms with explicit definitions, our proposed framework can ensure like-to-like comparisons of previous terms used in the literature. The practical goal of this framework is to aid athletes, coaches, and support staff to gain a better understanding of how the different types of movement variability within sporting tasks contribute to performance. The framework may allow training methods to be tailored to optimise the specific aspects of movement variability that contribute to success. This review was retrospectively registered using the Open Science Framework (OSF) Registries (https://osf.io/q73fd).