bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multimodality imaging of renal lymphoma and its mimics
Authors: Nguyen Trinh , Gupta Akshya , Bhatt Shweta 
Published: August 2022

AbstractLymphomatous involvement of the genitourinary system, particularly the kidneys, is commonly detected on autopsies; yet on conventional diagnostic imaging renal lymphoma is significantly underestimated and underreported, in part due to its variable imaging appearance and overlapping features with other conditions. We present a spectrum of typical and atypical appearances of renal lymphoma using multimodality imaging, while reviewing the roles of imaging in the detection, diagnosis, staging, and surveillance of patients with lymphoma. We also illustrate a breadth of benign and malignant entities with similar imaging features confounding the diagnosis of renal lymphoma, emphasizing the role of percutaneous image-guided biopsy. Understanding the spectrum of appearances of renal lymphoma and recognizing the overlapping entities will help radiologists improve diagnostic confidence and accuracy.
Cost-effectiveness of the implementation of [68Ga]Ga-PSMA-11 PET/CT at initial prostate cancer staging
Authors: van der Sar Esmée C. A. , Keusters Willem R. , van Kalmthout Ludwike W. M. , Braat Arthur J. A. T. , de Keizer Bart , Frederix Geert W. J. , Kooistra Anko , Lavalaye Jules , Lam Marnix G. E. H. , van Melick Harm H. E. 
Published: August 2022

Abstract
Background
Despite its high specificity, PSMA PET/CT has a moderate to low sensitivity of 40–50% for pelvic lymph node detection, implicating that a negative PSMA PET/CT cannot rule out lymph node metastases. This study investigates a strategy of implementing PSMA PET/CT for initial prostate cancer staging and treatment planning compared to conventional diagnostics. In this PSMA PET/CT strategy, a bilateral extended pelvic lymph node dissection (ePLND) is only performed in case of a negative PSMA PET/CT; in case of a positive scan treatment planning is solely based on PSMA PET/CT results.

Method
A decision table and lifetime state transition model were created. Quality-adjusted life years and health care costs were modelled over lifetime.

Results
The PSMA PET/CT strategy of treatment planning based on initial staging with [68Ga]Ga-PSMA-11 PET/CT results in cost-savings of €674 and a small loss in quality of life (QoL), 0.011 QALY per patient. The positive effect of [68Ga]Ga-PSMA-11 PET/CT was caused by abandoning both an ePLND and unnecessary treatment in iM1 patients, saving costs and resulting in higher QoL. The negative effect was caused by lower QoL and high costs in the false palliative state, due to pN1lim patients (≤ 4 pelvic lymph node metastases) being falsely diagnosed as iN1ext (> 4 pelvic lymph node metastases). These patients received subsequently palliative treatment instead of potentially curative therapy.

Conclusion
Initial staging and treatment planning based on [68Ga]Ga-PSMA-11 PET/CT saves cost but results in small QALY loss due to the rate of false positive findings.
Mesenchymal stromal cells pretreated with proinflammatory cytokines enhance skin wound healing via IL-6-dependent M2 polarization
Authors: Liu Chenyang , Xu Yan , Lu Yichi , Du Pan , Li Xiaoxiao , Wang Chengchun , Guo Peng , Diao Ling , Lu Guozhong 
Published: August 2022

AbstractBackgroundNumerous studies have shown that mesenchymal stromal cells (MSCs) promote cutaneous wound healing via paracrine signaling. Our previous study found that the secretome of MSCs was significantly amplified by treatment with IFN-γ and TNF-α (IT). It has been known that macrophages are involved in the initiation and termination of inflammation, secretion of growth factors, phagocytosis, cell proliferation, and collagen deposition in wound, which is the key factor during wound healing. In this study, we aim to test whether the supernatant of MSCs pretreated with IT (S-IT MSCs) possesses a more pronounced effect on improving wound healing and describe the interplay between S-IT MSCs and macrophages as well as the potential mechanism in skin wound healing.MethodsIn the present study, we used a unique supernatant of MSCs from human umbilical cord-derived MSCs (UC-MSCs) pretreated with IT, designated S-IT MSCs, subcutaneously injected into a mice total skin excision. We evaluated the effect of S-IT MSCs on the speed and quality of wound repair via IT MSCs-derived IL-6-dependent M2 polarization in vivo by hematoxylin–eosin staining (H&E), immunohistochemistry (IHC), immunofluorescence (IF), Masson’s trichrome staining, Sirius red staining, quantitative real-time PCR (qPCR). In addition, the effect of S-IT MSCs on the polarization of macrophages toward M2 phenotype and the potential mechanism of it were also investigated in vitro by flow cytometry (FCM), enzyme-linked immunosorbent assay (ELISA), tube formation assay, and western blot analysis.ResultsCompared with control supernatant (S-MSCs), our H&E and IF results showed that S-IT MSCs were more effectively in promoting macrophages convert to the M2 phenotype and enhancing phagocytosis of M2 macrophages. Meanwhile, the results of tube formation assay, IHC, Masson’s trichrome staining, Sirius red staining showed that the abilities of M2 phenotype to promote vascularization and collagen deposition were significantly enhanced by S-IT MSCs-treated, thereby accelerating higher quality wound healing. Further, our ELISA, FCM, qPCR and western blot results showed that IL-6 was highly enriched in S-IT MSCs and acted as a key regulator to induce macrophages convert to the M2 phenotype through IL-6-dependent signaling pathways, ultimately achieving the above function of promoting wound repair.ConclusionsThese findings provide the first evidence that the S-IT MSCs is more capable of eliciting M2 polarization of macrophages via IL-6-dependent signaling pathways and accelerating wound healing, which may represent a new strategy for optimizing the therapeutic effect of MSCs on wound healing.
How the mechanical microenvironment of stem cell growth affects their differentiation: a review
Authors: Zhang Xiaofang , Zhang Sibo , Wang Tianlu 
Published: August 2022

AbstractStem cell differentiation is of great interest in medical research; however, specifically and effectively regulating stem cell differentiation is still a challenge. In addition to chemical factors, physical signals are an important component of the stem cell ecotone. The mechanical microenvironment of stem cells has a huge role in stem cell differentiation. Herein, we describe the knowledge accumulated to date on the mechanical environment in which stem cells exist, which consists of various factors, including the extracellular matrix and topology, substrate stiffness, shear stress, hydrostatic pressure, tension, and microgravity. We then detail the currently known signalling pathways that stem cells use to perceive the mechanical environment, including those involving nuclear factor-kB, the nicotinic acetylcholine receptor, the piezoelectric mechanosensitive ion channel, and hypoxia-inducible factor 1α. Using this information in clinical settings to treat diseases is the goal of this research, and we describe the progress that has been made. In this review, we examined the effects of mechanical factors in the stem cell growth microenvironment on stem cell differentiation, how mechanical signals are transmitted to and function within the cell, and the influence of mechanical factors on the use of stem cells in clinical applications.
Single-cell transcriptomics reveals the cell fate transitions of human dopaminergic progenitors derived from hESCs
Authors: Liang Lingmin , Tian Yao , Feng Lin , Wang Chaoqun , Feng Guihai , Stacey Glyn Nigel , Shyh-Chang Ng , Wu Jun , Hu Baoyang , Li Wei , Hao Jie , Wang Liu , Wang Yukai 
Published: August 2022

Abstract
Background
Midbrain dopaminergic (DA) progenitors derived from human pluripotent stem cells are considered to be a promising treatment for Parkinson’s disease (PD). However, the differentiation process produces undesired cell types, which influence the in vivo evaluation of DA cells. In this paper, we analyze the cell fate choice during differentiation and provide valuable information on cell preparation.

Methods
Human embryonic stem cells were differentiated into DA progenitors. We applied single-cell RNA sequencing (scRNA-seq) of the differentiation cells at different time points and investigated the gene expression profiles. Based on the differentially expressed genes between DA and non-DA cells, we investigated the impact of LGI1 (DA enriched) overexpression on DA differentiation and the enrichment effect of CD99 (non-DA enriched) sorting.

Results
Transcriptome analyses revealed the DA differentiation trajectory as well as non-DA populations and three key lineage branch points. Using genetic gain- and loss-of-function approaches, we found that overexpression of LGI1, which is specific to EN1+ early DA progenitors, can promote the generation of TH+ neurons. We also found that choroid plexus epithelial cells and DA progenitors are major components of the final product (day 25), and CD99 was a specific surface marker of choroid plexus epithelial cells. Sorting of CD99− cells eliminated major contaminant cells and improved the purity of DA progenitors.

Conclusions
Our study provides the single-cell transcriptional landscape of in vitro DA differentiation, which can guide future improvements in DA preparation and quality control for PD cell therapy.
Biological activity reduction and mitochondrial and lysosomal dysfunction of mesenchymal stem cells aging in vitro
Authors: Zhang Ge , Wang Yuli , Lin Jianhua , Wang Bo , Mohsin Ali , Cheng Zhimin , Hao Weijie , Gao Wei-Qiang , Xu Huiming , Guo Meijin 
Published: August 2022

Abstract
Background
Mesenchymal stem cells (MSCs) have been extensively used for the treatment of various diseases in preclinical and clinical trials. In vitro propagation is needed to attain enough cells for clinical use. However, cell aging and viability reduction caused by long-time culture have not been thoroughly investigated, especially for the function of mitochondria and lysosomes. Therefore, this study was designed to detect mitochondrial and lysosomal activity, morphological and functional changes in human umbilical cord MSCs (UMSCs) after long-time culture.

Methods
First, we examined cell activities, including proliferation and immigration ability, differentiation potential, and immunosuppressive capacity of UMSCs at an early and late passages as P4 (named UMSC-P4) and P9 (named UMSC-P9), respectively. Then, we compared the mitochondrial morphology of UMSC-P4 and UMSC-P9 using the electronic microscope and MitoTracker Red dyes. Furthermore, we investigated mitochondrial function, including mitochondrial membrane potential, antioxidative ability, apoptosis, and ferroptosis detected by respective probe. Cell energy metabolism was tested by mass spectrometry. In addition, we compared the lysosomal morphology of UMSC-P4 and UMSC-P9 by electronic microscope and lysoTracker Red dyes. Finally, the transcriptome sequence was performed to analyze the total gene expression of these cells.

Results
It was found that UMSC-P9 exhibited a reduced biological activity and showed an impaired mitochondrial morphology with disordered structure, reduced mitochondrial crista, and mitochondrial fragments. They also displayed decreased mitochondrial membrane potential, antioxidative ability, tricarboxylic acid cycle activity and energy production. At the same time, apoptosis and ferroptosis were increased. In addition, UMSC-P9, relative to UMSC-P4, showed undegraded materials in their lysosomes, the enhancement in lysosomal membrane permeability, the reduction in autophagy and phagocytosis. Moreover, transcriptome sequence analysis also revealed a reduction of cell function, metabolism, mitochondrial biogenesis, DNA replication and repair, and an increase of gene expression related to cell senescence, cancer, diseases, and infection in UMSC-P9.

Conclusion
This study indicates that in vitro long-time culturing of MSCs can cause mitochondrial and lysosomal dysfunction, probably contributing to the decline of cell activity and cell aging. Therefore, the morphology and function of mitochondria and lysosomes can be regarded as two important parameters to monitor cell viability, and they can also serve as two important indicators for optimizing in vitro culture conditions.
Using Jupyter Notebooks for re-training machine learning models
Authors: Smajić Aljoša , Grandits Melanie , Ecker Gerhard F. 
Published: August 2022

AbstractMachine learning (ML) models require an extensive, user-driven selection of molecular descriptors in order to learn from chemical structures to predict actives and inactives with a high reliability. In addition, privacy concerns often restrict the access to sufficient data, leading to models with a narrow chemical space. Therefore, we propose a framework of re-trainable models that can be transferred from one local instance to another, and further allow a less extensive descriptor selection. The models are shared via a Jupyter Notebook, allowing the evaluation and implementation of a broader chemical space by keeping most of the tunable parameters pre-defined. This enables the models to be updated in a decentralized, facile, and fast manner. Herein, the method was evaluated with six transporter datasets (BCRP, BSEP, OATP1B1, OATP1B3, MRP3, P-gp), which revealed the general applicability of this approach.
OpenVar: functional annotation of variants in non-canonical open reading frames
Authors: Brunet Marie A. , Leblanc Sébastien , Roucou Xavier 
Published: August 2022

Abstract
Background
Recent technological advances have revealed thousands of functional open reading frames (ORF) that have eluded reference genome annotations. These overlooked ORFs are found throughout the genome, in any reading frame of transcripts, mature or non-coding, and can overlap annotated ORFs in a different reading frame. The exploration of these novel ORFs in genomic datasets and of their role in genetic traits is hindered by a lack of software.

Results
Here, we present OpenVar, a genomic variant annotator that mends that gap and fosters meaningful discoveries. To illustrate the potential of OpenVar, we analysed all variants within SynMicDB, a database of cancer-associated synonymous mutations. By including non-canonical ORFs in the analysis, OpenVar yields a 33.6-fold, 13.8-fold and 8.3-fold increase in high impact variants over Annovar, SnpEff and VEP respectively. We highlighted an overlapping non-canonical ORF in the HEY2 gene where variants significantly clustered.

Conclusions
OpenVar integrates non-canonical ORFs in the analysis of genomic variants, unveiling new research avenues to better understand the genotype–phenotype relationships.
Kinetics of capillary refill time after fluid challenge
Authors: Raia Lisa , Gabarre Paul , Bonny Vincent , Urbina Tomas , Missri Louai , Boelle Pierre-Yves , Baudel Jean-Luc , Guidet Bertrand , Maury Eric , Joffre Jeremie , Ait-Oufella Hafid 
Published: August 2022

Abstract
Background
Capillary refill time (CRT) is a valuable tool for triage and to guide resuscitation. However, little is known about CRT kinetics after fluid infusion.

Methods
We conducted a prospective observational study in a tertiary teaching hospital. First, we analyzed the intra-observer variability of CRT. Next, we monitored fingertip CRT in sepsis patients during volume expansion within the first 24 h of ICU admission. Fingertip CRT was measured every 2 min during 30 min following crystalloid infusion (500 mL over 15 min).

Results
First, the accuracy of repetitive fingertip CRT measurements was evaluated on 40 critically ill patients. Reproducibility was excellent, with an intra-class correlation coefficient of 99.5% (CI 95% [99.3, 99.8]). A CRT variation larger than 0.2 s was considered as significant. Next, variations of CRT during volume expansion were evaluated on 29 septic patients; median SOFA score was 7 [5–9], median SAPS II was 57 [45–72], and ICU mortality rate was 24%. Twenty-three patients were responders as defined by a CRT decrease  > 0.2 s at 30 min after volume expansion, and 6 were non-responders. Among responders, we observed that fingertip CRT quickly improved with a significant decrease at 6–8 min after start of crystalloid infusion, the maximal improvement being observed after 10–12 min (−0.7 [−0.3;−0.9] s) and maintained at 30 min. CRT variations significantly correlated with baseline CRT measurements (R = 0.39, P = 0.05).

Conclusions
CRT quickly improved during volume expansion with a significant decrease 6–8 min after start of fluid infusion and a maximal drop at 10–12 min.
Thoracolumbar retrolaminar block in seven dogs undergoing spinal surgery
Authors: Pentsou Kyratsoula , Huuskonen Vilhelmiina 
Published: August 2022

AbstractBackgroundThoracolumbar intervertebral disc extrusion is a common neurologic complaint in dogs and is associated with debilitating pain that requires careful analgesic management to avoid the transition to a chronic pain state. Recently, there has been an increased effort to incorporate regional anaesthetic techniques whenever possible, both for perioperative analgesia management and for prevention of chronic pain. A novel regional anaesthetic technique named retrolaminar block is a fascial plane block where the local anaesthetic is injected directly on top of the dorsal aspect of the vertebral lamina, in the fascial plane between the lamina and the epaxial muscles. The technique was recently described in humans and it is claimed to provide analgesia in patients undergoing thoracic and lumbar procedures. To the authors’ knowledge, the retrolaminar block has not been previously reported in live dogs.Case presentationSeven dogs presented to our hospital for suspected thoracolumbar intervertebral disc extrusion were anaesthetised using an anaesthetic premedication and induction protocol tailored for each individual animal. Once the suspected diagnosis was confirmed, all seven dogs were placed in sternal recumbency, and the target thoracolumbar vertebral spinous process was identified with palpation. A unilateral retrolaminar block was performed in all dogs with 2 mg/kg of 0.25% bupivacaine. Physiologic parameters, as well as responses to nociceptive stimuli, were monitored throughout the anaesthetic event.Intraoperatively, one dog required a bolus of fentanyl to control nociceptive stimulation while the epaxial muscles were retracted. No further intraoperative rescue analgesia was required in any of the cases. The postoperative pain was assessed using the Short Form of Glasgow Composite Measure Pain Scale for dogs every four hours for the duration of the dogs’ hospitalization. The retrolaminar block reduced the intraoperative requirement for systemic opioids and other adjunct analgesic agents and all dogs were comfortable throughout their hospitalization and up until the time of their discharge.ConclusionsThis case report presents the performance of the retrolaminar block technique as part of multimodal analgesia management in seven dogs undergoing thoracolumbar spinal surgery.
Impact of CCI on performance analysis of downlink satellite-terrestrial systems: outage probability and ergodic capacity perspective
Authors: Nguyen Nhat-Tien , Nguyen Hong-Nhu , Le Anh-Tu , Nguyen Nhan Duc , Do Dinh-Thuan , Voznak Miroslav 
Published: August 2022

AbstractThe evolution of non-orthogonal multiple access (NOMA) has raised many opportunities for massive connectivity with less latency in signal transmissions at great distances. We aim to integrate NOMA with a satellite communications network to evaluate system performance under the impacts of imperfect channel state information and co-channel interference from nearby systems. In our considered system, two users perform downlink communications under power-domain NOMA. We analyzed the performance of this system with two modes of shadowing effect: heavy shadowing and average shadowing. The detailed performance was analyzed in terms of the outage probability and ergodic capacity of the system. We derive closed-form expressions and performed a numerical analysis. We discover that the performance of two destinations depends on the strength of the transmit power at the satellite. However, floor outage occurs because the system depends on other parameters, such as satellite link modes, noise levels, and the number of interference sources. To verify the authenticity of the derived closed-form expressions, we also perform Monte-Carlo simulations.
Effects of aerobic, resistance, and combined training on endothelial function and arterial stiffness in older adults: study protocol for a systematic review and meta-analysis
Authors: da Silva Raphael S. N. , da Silva Diego S. , Waclawovsky Gustavo , Schaun Maximiliano I. 
Published: August 2022

Abstract
Introduction
Aging is an independent risk factor for cardiovascular events. It promotes vascular dysfunction which is associated with risk factors for cardiovascular diseases (CVDs). Exercise can modulate vascular function parameters, but little is known about the effects of different modalities of training (aerobic, resistance, and combined) on endothelial function and arterial stiffness in older adults.

Methods
This systematic review study will include randomized controlled trials (RCTs) selected from the electronic databases MEDLINE (PubMed), Cochrane, LILACS, EMBASE, and Web of Science. We will follow the PRISMA guidelines and PICOS framework. Studies involving both male and female older adults (≥60 years old) with or without comorbidities undergoing aerobic, resistance, and/or combined training compared to a control group (no exercise) will be eligible. We will use the Cochrane Risk of Bias 2 (RoB 2) tool to evaluate the quality of individual studies and GRADE to assess the strength of evidence. Statistical analyses will be conducted with RStudio for Windows (v1.3.959) using R package meta.

Discussion
A systematic review and meta-analysis involving data from studies of older adults would deepen our understanding of vascular adaptations to exercise training in this population. It could provide new insights into how health providers can improve patient management and prevention of cardiovascular events in older adults.

Systematic review registration
PROSPERO 42021275451
Primary stent implantation for bilateral spontaneous cervical ICA dissections with hypoperfusion after 72 h from onset: a case report
Authors: Chen Yijie , Zhang Ningyuan , Chen Yigang , Zheng Xu , Jin Xing , Zhang Jinhua 
Published: August 2022

Abstract
Background
Spontaneous cervical internal carotid artery dissection (cICAD) is a common cause of stroke in young adults. Endovascular therapy is an indispensable treatment for cICAD in some cases, but it faces great challenges.

Case presentation
A bilateral spontaneous cICADs with hypoperfusion-related AIS after 72 h from the onset was presented herein. The patient responded well to primary Solitaire stent detachment at the critical flow-limiting site.

Conclusions
Primary stent implantation at the critical flow-limiting site rather than covering the entire dissection may be a therapeutic option in spontaneous cICAD complicated with cerebral hypoperfusion. The Solitaire stent may be a good choice at the acute and subacute stages of cICAD.