bluuebunny/crossref_metadata_2025_split huggingface dataset:
Accuracy measures of 1.5-tesla MRI for the diagnosis of ACL, meniscus and articular knee cartilage damage and characteristics of false negative lesions: a level III prognostic study
Authors: Koch Jonathan E. J. , Ben-Elyahu Ron , Khateeb Basel , Ringart Michael , Nyska Meir , Ohana Nissim , Mann Gideon , Hetsroni Iftach 
Published: January 2021

Abstract
Background
MRI is the most accurate imaging modality for diagnosing knee pathologies. However, there is uncertainty concerning factors predicting false negative MRI, such as meniscal tear patterns as well as patient factors. The aims of this study were to report 1.5-Tesla MRI accuracy of ACL, meniscus and articular cartilage damage and characterize false negative lesions.

Methods
Two hundred eighteen consecutive knee arthroscopies performed in our institution between 2013 and 2016 and their respective prospectively-collected MRI reports were reviewed. Inclusion criteria were age > 15 years-old, primary arthroscopy, 1.5-Tesla MRI performed at the same institution, and time interval MRI-surgery < 6 months. Exclusion criteria were revision arthroscopy and arthroscopic-assisted fracture fixation or multiligament surgery. Accuracy measures and Kappa coefficients were calculated comparing the MRI diagnosis to the arthroscopic findings. Moreover, the arthroscopic findings of false negative MRI were compared to the findings of true positive MRI using the Fisher-exact test. Pearson correlation was used for testing the correlation between MRI accuracy and patient age.

Results
The highest accuracy was observed in medial meniscus and in ACL findings. For the medial meniscus sensitivity, specificity, agreement, and Kappa coefficient were 77, 92, 86%, and 0.7, and for the ACL these measures were 82, 97, 87%, and 0.73. MRI accuracy was lower in the lateral meniscus and articular cartilage with Kappa coefficient 0.42 and 0.3, respectively. More specifically, short peripheral tears in the posterior horn of the medial meniscus were characteristic of false negative findings compared to true positive findings of the MRI (p <  0.01). MRI accuracy correlated negatively compared to arthroscopic findings with patient age for the medial meniscus (r = − 0.21, p = 0.002) and for articular cartilage damage (r = − 0.45, p <  0.001).

Conclusion
1.5-Tesla MRI will accurately diagnose ACL and medial meniscal tears and can reliably complete the diagnostic workup following physical examination, particularly in young adults. This modality however is not reliable for diagnosing short peripheral tears at the posterior horn of the medial meniscus and partial thickness articular cartilage lesion of the femoral condyles. For these lesions, definitive diagnosis may require cartilage-specific MRI sequences or direct arthroscopic evaluation.

Level of evidence
Prognostic study, Level III.
Using text analysis software to identify determinants of inappropriate clinical question reporting and diagnostic procedure referrals in Reggio Emilia, Italy
Authors: Venturelli Francesco , Ottone Marta , Pignatti Fabio , Bellocchio Eletta , Pinotti Mirco , Besutti Giulia , Djuric Olivera , Giorgi Rossi Paolo 
Published: January 2021

Abstract
Background
Inappropriate prescribing of diagnostic procedures leads to overdiagnosis, overtreatment and resource waste in healthcare systems. Effective strategies to measure and to overcome inappropriateness are essential to increasing the value and sustainability of care.
We aimed to describe the determinants of inappropriate reporting of the clinical question and of inappropriate imaging and endoscopy referrals through an analysis of general practitioners’ (GP) referral forms in the province of Reggio Emilia, Italy.

Methods
A clinical audit was conducted on routinely collected referral forms of all GPs of Reggio Emilia province. All prescriptions for gastroscopy, colonoscopy, neurological and musculoskeletal computerised tomography (CT) and magnetic resonance imaging (MRI) from 2012 to 2017 were included. The appropriateness of referral forms was assessed using Clinika VAP software, which combines semantic analysis of clinical questions and available metadata. Local protocols agreed on by all physicians defined criteria of appropriateness. Two multilevel logistic models were used to identify multiple predictors of inappropriateness of referral forms and to analyse variability among GPs, primary care subdistricts and healthcare districts.

Results
Overall, 37% of referral forms were classified as inappropriate, gastroscopy and CT showed higher proportions of inappropriate referrals compared to colonoscopy and MRI. Inappropriateness increased with patient age for CT and MRI; for gastroscopy, it was lower for patients aged 65–84 compared to those younger, and for colonoscopy, it was higher for older patients. Fee exemptions were associated with inappropriateness in MRI referral forms. The effect of GPs’ practice organization was consistent across all tests, showing higher inappropriateness for primary care medical networks than in primary care medical groups. Male GPs were associated with inappropriateness in endoscopy, and older GPs were associated with inappropriateness in musculoskeletal CT. While there was moderate variability in the inappropriate prescribing among GPs, there was not among the healthcare districts or primary care subdistricts.

Conclusions
Routinely collected data and IT tools can be useful to identify and monitor diagnostic procedures at high risk of inappropriate prescribing. Assessing determinants of inappropriate referral makes it possible to tailor educational and organizational interventions to those who need them.
XenoCell: classification of cellular barcodes in single cell experiments from xenograft samples
Authors: Cheloni Stefano , Hillje Roman , Luzi Lucilla , Pelicci Pier Giuseppe , Gatti Elena 
Published: January 2021

Abstract
Background
Single-cell sequencing technologies provide unprecedented opportunities to deconvolve the genomic, transcriptomic or epigenomic heterogeneity of complex biological systems. Its application in samples from xenografts of patient-derived biopsies (PDX), however, is limited by the presence of cells originating from both the host and the graft in the analysed samples; in fact, in the bioinformatics workflows it is still a challenge discriminating between host and graft sequence reads obtained in a single-cell experiment.

Results
We have developed XenoCell, the first stand-alone pre-processing tool that performs fast and reliable classification of host and graft cellular barcodes from single-cell sequencing experiments. We show its application on a mixed species 50:50 cell line experiment from 10× Genomics platform, and on a publicly available PDX dataset obtained by Drop-Seq.

Conclusions
XenoCell accurately dissects sequence reads from any host and graft combination of species as well as from a broad range of single-cell experiments and platforms. It is open source and available at https://gitlab.com/XenoCell/XenoCell.
Mitotic arrest affects clustering of tumor cells
Authors: Bonnet Julia , Rigal Lise , Mondesert Odile , Morin Renaud , Corsaut Gaëlle , Vigneau Mathieu , Ducommun Bernard , Lobjois Valérie 
Published: January 2021

Abstract
Background
Cancer cell aggregation is a key process involved in the formation of tumor cell clusters. It has recently been shown that clusters of circulating tumor cells (CTCs) have an increased metastatic potential compared to isolated circulating tumor cells. Several widely used chemotherapeutic agents that target the cytoskeleton microtubules and cause cell cycle arrest at mitosis have been reported to modulate CTC number or the size of CTC clusters.

Results
In this study, we investigated in vitro the impact of mitotic arrest on the ability of breast tumor cells to form clusters. By using live imaging and quantitative image analysis, we found that MCF-7 cancer cell aggregation is compromised upon incubation with paclitaxel or vinorelbine, two chemotherapeutic drugs that target microtubules. In line with these results, we observed that MCF-7 breast cancer cells experimentally synchronized and blocked in metaphase aggregated poorly and formed loose clusters. To monitor clustering at the single-cell scale, we next developed and validated an in vitro assay based on live video-microscopy and custom-designed micro-devices. The study of cluster formation from MCF-7 cells that express the fluorescent marker LifeAct-mCherry using this new assay allowed showing that substrate anchorage-independent clustering of MCF-7 cells was associated with the formation of actin-dependent highly dynamic cell protrusions. Metaphase-synchronized and blocked cells did not display such protrusions, and formed very loose clusters that failed to compact.

Conclusions
Altogether, our results suggest that mitotic arrest induced by microtubule-targeting anticancer drugs prevents cancer cell clustering and therefore, could reduce the metastatic potential of circulating tumor cells.
Targeting B7-H3 via chimeric antigen receptor T cells and bispecific killer cell engagers augments antitumor response of cytotoxic lymphocytes
Authors: Liu Jie , Yang Shuo , Cao Bihui , Zhou Guangyu , Zhang Fengjuan , Wang Yuan , Wang Rixin , Zhu Lipeng , Meng Ya , Hu Cong , Liang Hui , Lin Xu , Zhu Kangshun , Chen Guokai , Luo Kathy Qian , Di Lijun , Zhao Qi 
Published: January 2021

Abstract
Background
B7-H3, an immune-checkpoint molecule and a transmembrane protein, is overexpressed in non-small cell lung cancer (NSCLC), making it an attractive therapeutic target. Here, we aimed to systematically evaluate the value of B7-H3 as a target in NSCLC via T cells expressing B7-H3-specific chimeric antigen receptors (CARs) and bispecific killer cell engager (BiKE)-redirected natural killer (NK) cells.

Methods
We generated B7-H3 CAR and B7-H3/CD16 BiKE derived from an anti-B7-H3 antibody omburtamab that has been shown to preferentially bind tumor tissues and has been safely used in humans in early-phase clinical trials. Antitumor efficacy and induced-immune response of CAR and BiKE were evaluated in vitro and in vivo. The effects of B7-H3 on aerobic glycolysis in NSCLC cells were further investigated.

Results
B7-H3 CAR-T cells effectively inhibited NSCLC tumorigenesis in vitro and in vivo. B7-H3 redirection promoted highly specific T-cell infiltration into tumors. Additionally, NK cell activity could be specially triggered by B7-H3/CD16 BiKE through direct CD16 signaling, resulting in significant increase in NK cell activation and target cell death. BiKE improved antitumor efficacy mediated by NK cells in vitro and in vivo, regardless of the cell surface target antigen density on tumor tissues. Furthermore, we found that anti-B7-H3 blockade might alter tumor glucose metabolism via the reactive oxygen species-mediated pathway.

Conclusions
Together, our results suggest that B7-H3 may serve as a target for NSCLC therapy and support the further development of two therapeutic agents in the preclinical and clinical studies.
The feasibility and reliability of actigraphy to monitor sleep in intensive care patients: an observational study
Authors: Delaney L. J. , Litton E. , Melehan K. L. , Huang H.-C. C. , Lopez V. , Van Haren F. 
Published: January 2021

AbstractBackgroundSleep amongst intensive care patients is reduced and highly fragmented which may adversely impact on recovery. The current challenge for Intensive Care clinicians is identifying feasible and accurate assessments of sleep that can be widely implemented. The objective of this study was to investigate the feasibility and reliability of a minimally invasive sleep monitoring technique compared to the gold standard, polysomnography, for sleep monitoring.MethodsProspective observational study employing a within subject design in adult patients admitted to an Intensive Care Unit. Sleep monitoring was undertaken amongst minimally sedated patients via concurrent polysomnography and actigraphy monitoring over a 24-h duration to assess agreement between the two methods; total sleep time and wake time.ResultsWe recruited 80 patients who were mechanically ventilated (24%) and non-ventilated (76%) within the intensive care unit. Sleep was found to be highly fragmented, composed of numerous sleep bouts and characterized by abnormal sleep architecture. Actigraphy was found to have a moderate level of overall agreement in identifying sleep and wake states with polysomnography (69.4%;K = 0.386,p < 0.05) in an epoch by epoch analysis, with a moderate level of sensitivity (65.5%) and specificity (76.1%). Monitoring accuracy via actigraphy was improved amongst non-ventilated patients (specificity 83.7%; sensitivity 56.7%). Actigraphy was found to have a moderate correlation with polysomnography reported total sleep time (r = 0.359,p < 0.05) and wakefulness (r = 0.371,p < 0.05). Bland–Altman plots indicated that sleep was underestimated by actigraphy, with wakeful states overestimated.ConclusionsActigraphy was easy and safe to use, provided moderate level of agreement with polysomnography in distinguishing between sleep and wakeful states, and may be a reasonable alternative to measure sleep in intensive care patients.Clinical Trial Registration numberACTRN12615000945527 (Registered 9/9/2015).
Evolutionary conservation and divergence of the human brain transcriptome
Authors: Pembroke William G. , Hartl Christopher L. , Geschwind Daniel H. 
Published: January 2021

AbstractBackgroundMouse models have allowed for the direct interrogation of genetic effects on molecular, physiological, and behavioral brain phenotypes. However, it is unknown to what extent neurological or psychiatric traits may be human- or primate-specific and therefore which components can be faithfully recapitulated in mouse models.ResultsWe compare conservation of co-expression in 116 independent data sets derived from human, mouse, and non-human primate representing more than 15,000 total samples. We observe greater changes occurring on the human lineage than mouse, and substantial regional variation that highlights cerebral cortex as the most diverged region. Glia, notably microglia, astrocytes, and oligodendrocytes are the most divergent cell type, three times more on average than neurons. We show that cis-regulatory sequence divergence explains a significant fraction of co-expression divergence. Moreover, protein coding sequence constraint parallels co-expression conservation, such that genes with loss of function intolerance are enriched in neuronal, rather than glial modules. We identify dozens of human neuropsychiatric and neurodegenerative disease risk genes, such as COMT, PSEN-1, LRRK2, SHANK3, and SNCA, with highly divergent co-expression between mouse and human and show that 3D human brain organoids recapitulate in vivo co-expression modules representing several human cell types.ConclusionsWe identify robust co-expression modules reflecting whole-brain and regional patterns of gene expression. Compared with those that represent basic metabolic processes, cell-type-specific modules, most prominently glial modules, are the most divergent between species. These data and analyses serve as a foundational resource to guide human disease modeling and its interpretation.
A comprehensive enhancer screen identifies TRAM2 as a key and novel mediator of YAP oncogenesis
Authors: Li Li , Ugalde Alejandro P. , Scheele Colinda L. G. J. , Dieter Sebastian M. , Nagel Remco , Ma Jin , Pataskar Abhijeet , Korkmaz Gozde , Elkon Ran , Chien Miao-Ping , You Li , Su Pin-Rui , Bleijerveld Onno B. , Altelaar Maarten , Momchev Lyubomir , Manber Zohar , Han Ruiqi , van Breugel Pieter C. , Lopes Rui , ten Dijke Peter , van Rheenen Jacco , Agami Reuven 
Published: January 2021

Abstract
Background
Frequent activation of the co-transcriptional factor YAP is observed in a large number of solid tumors. Activated YAP associates with enhancer loci via TEAD4-DNA-binding protein and stimulates cancer aggressiveness. Although thousands of YAP/TEAD4 binding-sites are annotated, their functional importance is unknown. Here, we aim at further identification of enhancer elements that are required for YAP functions.

Results
We first apply genome-wide ChIP profiling of YAP to systematically identify enhancers that are bound by YAP/TEAD4. Next, we implement a genetic approach to uncover functions of YAP/TEAD4-associated enhancers, demonstrate its robustness, and use it to reveal a network of enhancers required for YAP-mediated proliferation. We focus on EnhancerTRAM2, as its target gene TRAM2 shows the strongest expression-correlation with YAP activity in nearly all tumor types. Interestingly, TRAM2 phenocopies the YAP-induced cell proliferation, migration, and invasion phenotypes and correlates with poor patient survival. Mechanistically, we identify FSTL-1 as a major direct client of TRAM2 that is involved in these phenotypes. Thus, TRAM2 is a key novel mediator of YAP-induced oncogenic proliferation and cellular invasiveness.

Conclusions
YAP is a transcription co-factor that binds to thousands of enhancer loci and stimulates tumor aggressiveness. Using unbiased functional approaches, we dissect YAP enhancer network and characterize TRAM2 as a novel mediator of cellular proliferation, migration, and invasion. Our findings elucidate how YAP induces cancer aggressiveness and may assist diagnosis of cancer metastasis.
Further evaluation and validation of the VETSCAN IMAGYST: in-clinic feline and canine fecal parasite detection system integrated with a deep learning algorithm
Authors: Nagamori Yoko , Sedlak Ruth Hall , DeRosa Andrew , Pullins Aleah , Cree Travis , Loenser Michael , Larson Benjamin S. , Smith Richard Boyd , Penn Cory , Goldstein Richard 
Published: January 2021

AbstractBackgroundFecal examinations in pet cats and dogs are key components of routine veterinary practice; however, their accuracy is influenced by diagnostic methodologies and the experience level of personnel performing the tests. The VETSCAN IMAGYST system was developed to provide simpler and easier fecal examinations which are less influenced by examiners’ skills. This system consists of three components: a sample preparation device, an automated microscope scanner, and analysis software. The objectives of this study were to qualitatively evaluate the performance of the VETSCAN IMAGYST system on feline parasites (AncylostomaandToxocara cati) and protozoan parasites (CystoisosporaandGiardia) and to assess and compare the performance of the VETSCAN IMAGYST centrifugal flotation method to reference centrifugal and passive flotation methods.MethodsTo evaluate the diagnostic performance of the scanning and algorithmic components of the VETSCAN IMAGYST system, fecal slides were prepared by the VETSCAN IMAGYST centrifugal flotation technique with pre-screened fecal samples collected from dogs and cats and examined by both an algorithm and parasitologists. To assess the performance of the VETSCAN IMAGYST centrifugal flotation technique, diagnostic sensitivity and specificity were calculated and compared to those of conventional flotation techniques.ResultsThe performance of the VETSCAN IMAGYST algorithm closely correlated with evaluations by parasitologists, with sensitivity of 75.8–100% and specificity of 93.1-100% across the targeted parasites. For samples with 50 eggs or less per slide, Lin’s concordance correlation coefficients ranged from 0.70 to 0.95 across the targeted parasites. The results of the VETSCAN IMAGYST centrifugal flotation method correlated well with those of the conventional centrifugal flotation method across the targeted parasites: sensitivity of 65.7–100% and specificity of 97.6–100%. Similar results were observed for the conventional passive flotation method compared to the conventional centrifugal flotation method: sensitivity of 56.4–91.7% and specificity of 99.4–100%.ConclusionsThe VETSCAN IMAGYST scanning and algorithmic systems with the VETSCAN IMAGYST fecal preparation technique demonstrated a similar qualitative performance to the parasitologists’ examinations with conventional fecal flotation techniques. Given the deep learning nature of the VETSCAN IMAGYST system, its performance is expected to improve over time, enabling it to be utilized in veterinary clinics to perform fecal examinations accurately and efficiently.Graphical Abstract
Structural changes in the sacroiliac joint on MRI and relationship to ASDAS inactive disease in axial spondyloarthritis: a 2-year study comparing treatment with etanercept in EMBARK to a contemporary control cohort in DESIR
Authors: Maksymowych Walter P. , Claudepierre Pascal , de Hooge Manouk , Lambert Robert G. , Landewé Robert , Molto Anna , van der Heijde Désirée , Bukowski Jack F. , Jones Heather , Pedersen Ron , Szumski Annette , Vlahos Bonnie , Dougados Maxime 
Published: January 2021

Abstract
Background
Limited information is available on the impact of treatment with a tumor necrosis factor inhibitor (TNFi) on structural lesions in patients with recent-onset axial spondyloarthritis (axSpA). We compared 2-year structural lesion changes on magnetic resonance imaging (MRI) in the sacroiliac joints (SIJ) of patients with recent-onset axSpA receiving etanercept in a clinical trial (EMBARK) to similar patients not receiving biologics in a cohort study (DESIR). We also evaluated the relationship between the Ankylosing Spondylitis Disease Activity Score (ASDAS) and change in MRI structural parameters.

Methods
The difference between etanercept (EMBARK) and control (DESIR) in the net percentage of patients with structural lesion change was determined using the SpondyloArthritis Research Consortium of Canada SIJ Structural Score, with and without adjustment for baseline covariates. The relationship between sustained ASDAS inactive disease, defined as the presence of ASDAS < 1.3 for at least 2 consecutive time points 6 months apart, and structural lesion change was evaluated.

Results
This study included 163 patients from the EMBARK trial and 76 from DESIR. The net percentage of patients with erosion decrease was significantly greater for etanercept vs control: unadjusted: 23.9% vs 5.3%; P = 0.01, adjusted: 23.1% vs 2.9%; P = 0.01. For the patients attaining sustained ASDAS inactive disease on etanercept, erosion decrease was evident in significantly more than erosion increase: 34/104 (32.7%) vs 5/104 (4.8%); P < 0.001. A higher proportion had erosion decrease and backfill increase than patients in other ASDAS status categories. However, the trend across ASDAS categories was not significant and decrease in erosion was observed even in patients without a sustained ASDAS response.

Conclusions
These data show that a greater proportion of patients achieved regression of erosion with versus without etanercept. However, the link between achieving sustained ASDAS inactive disease and structural lesion change on MRI could not be clearly established.

Trial registration
EMBARK: ClinicalTrials.gov identifier: NCT01258738, Registered 13 December 2010; DESIR: ClinicalTrials.gov identifier: NCT01648907, Registered 24 July 2012.