bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Two-Step Diagnostic Approach for NTRK Gene Fusion Detection in Biliary Tract and Pancreatic Adenocarcinomas
Authors: Demols Anne , Rocq Laureen , Perez-Casanova Luis , Charry Manon , De Nève Nancy , Ramadhan Ali , Van Campenhout Claude , De Clercq Sarah , Maris Calliope , Closset Jean , Lucidi Valerio , Salmon Isabelle , D’Haene Nicky 
Published: March 2023

Abstract

Background
It is of interest to determine the incidence and molecular characteristics of NTRK gene fusions in patients with bilio-pancreatic cancers, because of possible treatment with TRK inhibitors for advanced tumors. The aim of the present study was to apply the guidelines for NTRK testing algorithm to a series of patients with bilio-pancreatic cancers.

Methods
Immunohistochemistry screening was applied on formalin-fixed paraffin-embedded archival blocks from surgical resections, biopsies, or cytological samples of biliary tract and pancreatic adenocarcinomas. The presence of at least a weak staining in rare tumor cells led to testing by 2 RNA-based NGS panels.

Results
For biliary tract tumors, 153 samples have been selected. A total of 140 samples were suitable to perform IHC, and 17 samples were IHC positive. RNA NGS testing of the 17 IHC-positive samples revealed a single NTRK3 gene fusion (ETV6(4)-NTRK3(14)) that was detected by both NGS panels. In this perihilar cholangiocarcinoma, IHC performed on a biopsy showed a weak focal cytoplasmic and nuclear staining. No other NTRK fusion was detected on the 16 other samples with both panels. Overall in the patients screened by IHC and confirmed by NGS, the percentage of NTRK fusions was 0.7%. For pancreatic cancers, 319 samples have been selected and 297 were suitable to perform IHC. Nineteen samples were IHC positive. No fusion was detected by NGS.

Conclusion
NTRK gene fusions are rare in bilio-pancreatic cancers but testing is of high interest due to possible treatment with specific TRK inhibitors.
Rethinking diagnosis-based service models for childhood neurodevelopmental disabilities in Canada: a question of equity
Authors: Ip Angie , Poon Brenda T , Oberlander Tim F 
Published: March 2023

Abstract
Neurodevelopmental disability in children covers a vast array of congenital and acquired long-term conditions associated with brain or neuromuscular impairments that impact function. While some presentations of neurodevelopmental disability align with diagnostic labels, many do not, leaving children whose conditions don’t fit neatly under diagnostic labels struggling to access services or families and professionals feeling pressured to assign a diagnostic label in order to access services. In this paper, we (1) discuss the evidence showing that there is often a mismatch between a child’s neurodevelopmental diagnosis, or lack of diagnosis, and function, (2) comment on the inequities exacerbated by diagnosis-based approaches for services, and (3) highlight the potential benefits of using a function and participation-based approach for providing services to children with neurodevelopmental disabilities. We close with three calls to action for function and participation-based approaches that could better support equitable services for children with neurodevelopmental disabilities.
Intermediate levels of asymptomatic transmission can lead to the highest epidemic fatalities
Authors: Park Sang Woo , Dushoff Jonathan , Grenfell Bryan T , Weitz Joshua S 
Published: March 2023

Abstract
Asymptomatic infections have hampered the ability to characterize and prevent the transmission of SARS-CoV-2 throughout the pandemic. Although asymptomatic infections reduce severity at the individual level, they can make population-level outcomes worse if asymptomatic individuals—unaware they are infected—transmit more than symptomatic individuals. Using an epidemic model, we show that intermediate levels of asymptomatic infection lead to the highest levels of epidemic fatalities when the decrease in symptomatic transmission, due either to individual behavior or mitigation efforts, is strong. We generalize this result to include presymptomatic transmission, showing that intermediate levels of nonsymptomatic transmission lead to the highest levels of fatalities. Finally, we extend our framework to illustrate how the intersection of asymptomatic spread and immunity profiles determine epidemic trajectories, including population-level severity, of future variants. In particular, when immunity provides protection against symptoms, but not against infections or deaths, epidemic trajectories can have faster growth rates and higher peaks, leading to more total deaths. Conversely, even modest levels of protection against infection can mitigate the population-level effects of asymptomatic spread.
Dual leucine zipper kinase is necessary for retinal ganglion cell axonal regeneration in Xenopus laevis
Authors: Fague Lindsay , Marsh-Armstrong Nicholas 
Published: March 2023

Abstract
Retinal ganglion cell (RGC) axons of the African clawed frog, Xenopus laevis, unlike those of mammals, are capable of regeneration and functional reinnervation of central brain targets following injury. Here, we describe a tadpole optic nerve crush (ONC) procedure and assessments of brain reinnervation based on live imaging of RGC-specific transgenes which, when paired with CRISPR/Cas9 injections at the one-cell stage, can be used to assess the function of regeneration-associated genes in vivo in F0 animals. Using this assay, we find that map3k12, also known as dual leucine zipper kinase (Dlk), is necessary for RGC axonal regeneration and acts in a dose-dependent manner. Loss of Dlk does not affect RGC innervation of the brain during development or visually driven behavior but does block both axonal regeneration and functional vision restoration after ONC. Dlk loss does not alter the acute changes in mitochondrial movement that occur within RGC axons hours after ONC but does completely block the phosphorylation and nuclear translocation of the transcription factor Jun within RGCs days after ONC; yet, Jun is dispensable for reinnervation. These results demonstrate that in a species fully capable of regenerating its RGC axons, Dlk is essential for the axonal injury signal to reach the nucleus but may affect regeneration through a different pathway than by which it signals in mammalian RGCs.
2B-AlertApp 2.0: personalized caffeine recommendations for optimal alertness
Authors: Vital-Lopez Francisco G , Doty Tracy J , Anlap Ian , Killgore William D S , Reifman Jaques 
Published: March 2023

AbstractStudy ObjectivesIf properly consumed, caffeine can safely and effectively mitigate the effects of sleep loss on alertness. However, there are no tools to determine the amount and time to consume caffeine to maximize its effectiveness. Here, we extended the capabilities of the 2B-Alert app, a unique smartphone application that learns an individual’s trait-like response to sleep loss, to provide personalized caffeine recommendations to optimize alertness.MethodsWe prospectively validated 2B-Alert’s capabilities in a 62-hour total sleep deprivation study in which 21 participants used the app to measure their alertness throughout the study via the psychomotor vigilance test (PVT). Using PVT data collected during the first 36 hours of the sleep challenge, the app learned the participant’s sleep-loss response and provided personalized caffeine recommendations so that each participant would sustain alertness at a pre-specified target level (mean response time of 270 milliseconds) during a 6-hour period starting at 44 hours of wakefulness, using the least amount of caffeine possible. Starting at 42 hours, participants consumed 0 to 800 mg of caffeine, per the app recommendation.Results2B-Alert recommended no caffeine to five participants, 100–400 mg to 11 participants, and 500–800 mg to five participants. Regardless of the consumed amount, participants sustained the target alertness level ~80% of the time.Conclusions2B-Alert automatically learns an individual’s phenotype and provides personalized caffeine recommendations in real time so that individuals achieve a desired alertness level regardless of their sleep-loss susceptibility.
Rapid and Live-Cell Detection of Senescence in Mesenchymal Stem Cells by Micro Magnetic Resonance Relaxometry
Authors: Thamarath Smitha Surendran , Tee Ching Ann , Neo Shu Hui , Yang Dahou , Othman Rashidah , Boyer Laurie A , Han Jongyoon 
Published: March 2023

Abstract
Detection of cellular senescence is important quality analytics of cell therapy products, including mesenchymal stromal cells (MSCs). However, its detection is critically limited by the lack of specific markers and the destructive assays used to read out these markers. Here, we establish a rapid, live-cell assay for detecting senescent cells in heterogeneous mesenchymal stromal cell (MSC) cultures. We report that the T2 relaxation time measured by microscale Magnetic Resonance Relaxometry, which is related to intracellular iron accumulation, correlates strongly with senescence markers in MSC cultures under diverse conditions, including different passages and donors, size-sorted MSCs by inertial spiral microfluidic device, and drug-induced senescence. In addition, the live-cell and non-destructive method presented here has general applicability to other cells and tissues and can critically advance our understanding of cellular senescence.
Quasi-Experimental Evidence on Carbon Pricing
Authors: Vrolijk Kasper , Sato Misato 
Published: March 2023

Abstract
A growing literature suggests that carbon emissions are most efficiently reduced by carbon pricing. The evidence base on the effectiveness of market-based mechanisms, however, faces three key limitations: studies often (a) predict, rather than evaluate effects, (b) show large difference in findings, and (c) cannot always infer causal relations. Quasi-experimental studies can address these challenges by using variation in policies over time, space, or entities. This paper systematically reviews this new literature, outlines the benefits and caveats of quasi-experimental methodologies, and verifies the reliability and value of quasi-experimental estimates. The overall evidence base documents a causal effect between carbon pricing and emission reductions, with ambiguous effects on economic outcomes, and there are important gaps and inconsistencies. This review underscores that estimates should be interpreted with care because of: (a) inappropriate choice of method, (b) incorrect implementation of empirical analysis (e.g., violate identifying assumptions), and (c) data limitations. More cross-learning across studies and use of novel empirical strategies is needed to improve the empirical evidence base going forward.
Implementing a Rapid Response Team
Authors: Jamous Sabat El , Kouatly Iman , Irani Joanna , Badr Lina Kurdahi 
Published: March 2023

Background
The benefits of rapid response teams (RRTs) have been controversial with few studies conducted in low- to middle-income countries.

Objective
The aim of this study was to investigate the effectiveness of implementing an RRT on 4 patient outcomes.

Methods
We conducted a quality improvement pre-and-post design using the Plan-Do-Study-Act model in a tertiary hospital in a low- to middle-income country. We collected data before and after implementing the RRT in 4 phases and over 4 years.

Results
Survival to discharge after cardiac arrest was 25.0% per 1000 discharges in 2016 and increased to 50% in 2019, a 50% increase. The rate of activations per 1000 discharges was 20.45% for the code team in 2016 and 33.6% for the RRT team in 2019. Thirty-one patients who arrested were transferred to a critical care unit before implementing the RRT, and 33% of such patients were transferred after. The time it took the code team to arrive at the bedside was 3.1 minutes in 2016 and decreased to 1.7 minutes for the RRT team to arrive in 2019, a 46% decrease.

Discussion and Clinical Implications
Implementing an RTT led by nurses in a low- to middle-income country increased the survival rate of patients who had a cardiac arrest by 50%. The role of nurses in improving patient outcomes and saving lives is substantial and empowers nurses to call for assistance to save patient lives who show early signs of a cardiac arrest. Hospital administrators should continue to use strategies to improve nurses' timely response to the clinical deterioration of patients and to continue to collect data to assess the effect of the RRT over time.
Machine learning algorithm improves the detection of NASH (NAS-based) and at-risk NASH: A development and validation study
Authors: Lee Jenny , Westphal Max , Vali Yasaman , Boursier Jerome , Petta Salvatorre , Ostroff Rachel , Alexander Leigh , Chen Yu , Fournier Celine , Geier Andreas , Francque Sven , Wonders Kristy , Tiniakos Dina , Bedossa Pierre , Allison Mike , Papatheodoridis Georgios , Cortez-Pinto Helena , Pais Raluca , Dufour Jean-Francois , Leeming Diana Julie , Harrison Stephen , Cobbold Jeremy , Holleboom Adriaan G. , Yki-Järvinen Hannele , Crespo Javier , Ekstedt Mattias , Aithal Guruprasad P. , Bugianesi Elisabetta , Romero-Gomez Manuel , Torstenson Richard , Karsdal Morten , Yunis Carla , Schattenberg Jörn M. , Schuppan Detlef , Ratziu Vlad , Brass Clifford , Duffin Kevin , Zwinderman Koos , Pavlides Michael , Anstee Quentin M. , Bossuyt Patrick M. ,   on behalf of the LITMUS investigators
Published: March 2023

Background and Aims:
Detecting NASH remains challenging, while at-risk NASH (steatohepatitis and F≥ 2) tends to progress and is of interest for drug development and clinical application. We developed prediction models by supervised machine learning techniques, with clinical data and biomarkers to stage and grade patients with NAFLD.

Approach and Results:
Learning data were collected in the Liver Investigation: Testing Marker Utility in Steatohepatitis metacohort (966 biopsy-proven NAFLD adults), staged and graded according to NASH CRN. Conditions of interest were the clinical trial definition of NASH (NAS ≥ 4;53%), at-risk NASH (NASH with F ≥ 2;35%), significant (F ≥ 2;47%), and advanced fibrosis (F ≥ 3;28%). Thirty-five predictors were included. Missing data were handled by multiple imputations. Data were randomly split into training/validation (75/25) sets. A gradient boosting machine was applied to develop 2 models for each condition: clinical versus extended (clinical and biomarkers). Two variants of the NASH and at-risk NASH models were constructed: direct and composite models.
Clinical gradient boosting machine models for steatosis/inflammation/ballooning had AUCs of 0.94/0.79/0.72. There were no improvements when biomarkers were included. The direct NASH model produced AUCs (clinical/extended) of 0.61/0.65. The composite NASH model performed significantly better (0.71) for both variants. The composite at-risk NASH model had an AUC of 0.83 (clinical and extended), an improvement over the direct model. Significant fibrosis models had AUCs (clinical/extended) of 0.76/0.78. The extended advanced fibrosis model (0.86) performed significantly better than the clinical version (0.82).

Conclusions:
Detection of NASH and at-risk NASH can be improved by constructing independent machine learning models for each component, using only clinical predictors. Adding biomarkers only improved the accuracy of fibrosis.
Pentosan polysulfate sodium (Elmiron) maculopathy: a genetic perspective
Authors: Kalaw Fritz Gerald P. , Ignacio John Carlos I. , Wu Chris Y. , Ferreyra Henry , Nudleman Eric , Baxter Sally L. , Freeman William R. , Borooah Shyamanga 
Published: March 2023

ABSTRACT

Purpose:
To assess genetic associations for pentosan polysufate sodium maculopathy.

Methods:
Genetic testing for inherited retinal dystrophy (IRD) genes using exome testing and for 14 age-related macular degeneration (AMD) associated single nucleotide polymorphisms (SNP) using panel testing were performed. Additionally, full-field electroretinograms (ffERG) were obtained to identify any cone-rod dystrophy.

Results:
Eleven out of fifteen patients were female, with a mean age of 69 (range 46-85). IRD exome testing in five patients revealed six pathogenic variants but failed to confirm IRD in any patient genetically. FfERG performed in 12 patients demonstrated only non-specific a- and b-wave abnormalities in 11 cases and was normal in one case. For AMD SNPs, CFH rs3766405 (p=0.003) and CETP (p=0.027) were found to be statistically significantly associated with pentosan polysulfate maculopathy phenotype compared to the control population.

Conclusion:
Pentosan polysulfate maculopathy is not associated with Mendelian IRD genes. However, several AMD risk alleles were identified to be associated with maculopathy compared to their frequency in the normal population. This suggests a role for genes in disease pathology, particularly the alternative complement pathway. These findings would benefit from further investigation to understand the risk of developing maculopathy in taking pentosan polysulfate.
Evaluation of optic disc and macular vascularity changes in CRVO using optical coherence tomography angiography
Authors: Yousif Hussein , Rashad Mohammad , Abdel Dayem Hisham Khairy , Abdellatif Mona K 
Published: March 2023

ABSTRACT

Purpose:
To quantify changes in optic disc and macular vasculature in patients with central retinal vein occlusion (CRVO) using optical coherence tomography (OCT) angiography and detect its correlation with visual acuity (VA).

Methods:
The study included 20 eyes of 20 patients with treatment naïve CRVO and 20 age-matched controls. OCT and OCT angiography (OCTA) were performed on the macula and optic disc. Central 1 mm subfield foveal thickness (CSFT) was measured. Vascular densities (VD) of superficial and deep macular capillary plexuses with whole disc VD, inside disc VD and radial peripapillary capillary plexus (RPC) were analyzed. Macular ischemia was evaluated by fundus fluorescein angiography (FFA). VA was correlated with measured parameters.

Results:
All measured macular and disc VDs differed significantly between cases and controls except inside disc VD. Visual acuity showed a highly significant negative correlation with whole disc VD (P = 0.005) and RPC (P = 0.002), borderline correlation with CSFT (P=0.06), and insignificant correlation with macular VDs. RPC VD showed a significant correlation with deep parafoveal (P=0.04), and superficial and deep perifoveal VDs (P=0.01).

Conclusion:
Optic disc VD could provide more accurate indication of retinal blood supply than macular VD in cases of CRVO with severe macular edema.
Pathways of Fluid Leakage in Age Related Macular Degeneration
Authors: Fouad Yousef A. , Santina Ahmad , Bousquet Elodie , Sadda Srinivas R. , Sarraf David 
Published: March 2023

Abstract
Age related macular degeneration is the most common cause of blindness in the western world and the development of intravitreal pharmacotherapies for the treatment of the neovascular complications of this disorder is considered a revolution in the care of this devastating disease. Anti-vascular endothelial growth factor (VEGF) agents such as ranibizumab and aflibercept can prevent blindness by reducing or resolving fluid in AMD and therefore the detection of these biomarkers (e.g. intraretinal and subretinal fluid) with high resolution, depth resolved tools such as optical coherence tomography (OCT) is a critical process in the successful management of this condition. However, there is growing evidence to indicate that fluid is not always the result of neovascular pathways and therefore the obligatory administration of anti-VEGF therapy in response to the observation of fluid on OCT may be flawed. Non-neovascular mechanisms of fluid leakage (e.g. retinal pigment epithelium pump impairment) should also be considered and in these circumstances anti-VEGF injection should be deferred. This editorial will review the neovascular and non-neovascular pathways of fluid leakage in AMD and will provide more informed guidance for the overall evaluation and management of exudation in AMD, including an observe and extend regimen in the context of non-neovascular fluid.
Hyperreflective band in the ganglion cell layer in retinitis pigmentosa
Authors: Antropoli Alessio , Arrigo Alessandro , Bianco Lorenzo , Cavallari Elena , Berni Alessandro , Casoni Filippo , Consalez Giacomo , Bandello Francesco , Cremona Ottavio , Battaglia Parodi Maurizio 
Published: March 2023

ABSTRACT

Purpose:
To describe a sign that takes the form of a continuous hyperreflective band within the thickness of the ganglion cell layer (GCL), thus dubbed the “hyperreflective ganglion cell layer band” (HGB), which we detected in a fraction of patients affected by retinitis pigmentosa (RP).

Methods:
Retrospective, cross-sectional, observational study. Optical coherence tomography (OCT) images of RP patients examined between May 2015 and June 2021 were retrospectively reviewed for the presence of HGB, epiretinal membrane (ERM), macular hole and cystoid macular edema (CME). The ellipsoid zone (EZ) width was also measured. A subgroup of patients underwent microperimetry in the central 2°,4° and 10°.

Results:
One hundred forty-four eyes from 77 subjects were included in the study. HGB was present in 39 (25.3%) RP eyes. Mean best-corrected visual acuity (BCVA) was 0.39 ± 0.05 logMAR (approximately 20/50 Snellen equivalent) and 0.18 ± 0.03 logMAR (approximately 20/32 Snellen equivalent) in eyes with and without HGB, respectively (p < 0.001). The two groups did not differ with regard to EZ width, mean 2°, 4° and 10° retinal sensitivity, and prevalence of CME, ERM and macular hole. The multivariable analysis showed the presence of HGB to be a predictor of poorer BCVA (p<0.001).

Conclusions:
HGB is an OCT finding detectable in approximately a quarter of RP eyes and is associated with a poorer visual function. In the discussion, we speculate about possible morphogenetic scenarios to explain this observation.
Future of virtual education and telementoring
Authors: Seddon Ian , Rosenberg Eric , Houston Steve K. 
Published: March 2023

Purpose of review
To summarize recent technological advancements in medical and surgical education and explore what the future of medicine might be as it relates to blockchain technology, the metaverse, and web3.

Recent findings
Through the use of digitally assisted ophthalmic surgery and high dynamic range 3D cameras, it is now possible to record and live stream 3D video content. Although the ‘metaverse’ is still in its early stages, there are a variety of proto-metaverse technologies that exist to facilitate user interactions that can mimic the real world through the use of shared digital environments and 3D spatial audio. Advanced blockchain technologies can allow for further development of interoperable virtual worlds where a user has an on-chain identity, credentials, data, assets, and much more that they can carry across platforms seamlessly.

Summary
As remote real-time communication becomes an integral part of human interaction, 3D live streaming has the potential to revolutionize ophthalmic education by removing traditional geographic and physical constraints of in-person surgical viewing. The incorporation of metaverse and web3 technologies has created new outlets for knowledge sharing that may improve how we operate, teach, learn, and transfer knowledge.