bluuebunny/crossref_metadata_2025_split huggingface dataset:
The PRIMARY Score
Authors: Guo Shikuan , Kang Fei , Ma Shuaijun , Jiao Jianhua , Ren Jing , Wang Jing , Zhang Jingliang , Qin Weijun 
Published: December 2023

Purpose
Multiparametric MRI is the current standard for detecting clinically significant prostate cancer (csPCa). However, men with negative or equivocal MRI often undergo unnecessary biopsies due to concerns about false-negative results. The recently proposed 68Ga-PSMA PET/CT-based PRIMARY score exhibited good diagnostic performance for csPCa. This study aimed to externally validate the performance of the PRIMARY score and evaluate its added diagnostic value to MRI triage in detecting csPCa.

Patients and Methods
This retrospective cohort study included 431 men who underwent both 68Ga-PSMA PET/CT and MRI before biopsy. Performance was assessed using the area under the receiver operating characteristic curve and the decision curve analysis. The PRIMARY score + MRI was considered positive for either PRIMARY score 3–5 or Prostate Imaging Reporting and Data System (PI-RADS) 4/5.

Results
The prevalence of csPCa was 51.7% (223/431). The area under the receiver operating characteristic curve of the 5-level PRIMARY score for csPCa was significantly higher than that of MRI (0.873 vs 0.786, P < 0.001). For the entire group, sensitivity, specificity, positive predictive value, and negative predictive value of the PRIMARY score were 90.6%, 61.1%, 71.4%, and 85.8%, respectively, which outperformed 87.9%, 49.0%, 64.9%, and 79.1% of PI-RADS on MRI. The PRIAMRY score + MRI improved sensitivity (96.0% vs 87.9%, P < 0.001) and negative predictive value (91.5% vs 79.1%, P < 0.001) without compromising specificity and positive predictive value compared with MRI alone. This combined approach avoided 24.6% (106/431) of unnecessary biopsies, while missing 4.0% (9/223) of csPCa cases. The addition of the PRIMARY score in men with PI-RADS 1–3 showed a net benefit, but not in men with PI-RADS 4/5.

Conclusions
The PRIMARY score was superior to MRI in detecting csPCa, and its added diagnostic value was in men with negative or equivocal MRI results. The PRIMARY score + MRI improved negative predictive value and sensitivity for csPCa compared with MRI alone. Further prospective trials will validate whether men with clinical suspicion of csPCa but negative PRIMARY score + MRI can safely avoid unnecessary biopsies.
Cognitive Symptom Awareness Among Patients With Multiple Sclerosis Using a Mobile Application
Authors: Miller Dena , Okai Annette , Scott Kathleen , Reynolds Staci S. 
Published: December 2023

Abstract

Purpose
Cognitive impairment is a common complication in persons with multiple sclerosis (MS). Using a mobile application has been shown to improve patient’s awareness of cognitive symptoms. The purpose of this quality improvement project was to improve awareness of cognitive symptoms in adult patients with MS using a mobile application.

Design
A pre/post-implementation quality improvement design was used.

Methods
Patients were instructed to download the application MS Care Connect. Patients completed a pre/post-questionnaire regarding their awareness of cognitive symptoms and if they were likely to discuss symptoms with providers. They were instructed to use the application to rate the severity of their cognitive symptoms at least weekly.

Results
Thirty-two patients completed both pre- and post-implementation questionnaires. No significant change in awareness of cognitive symptoms was found; however, patients were more likely to discuss cognitive changes with their healthcare team. In the 18 patients who used the application, a total of 60 cognitive symptom ratings were reported.

Clinical Relevance to the Practice of Rehabilitation Nursing
Nurses may recommend use of a mobile application for patients to track their cognitive symptoms; however, further research is needed.

Conclusion
This project showed that adding a mobile application did not change awareness of patients’ cognitive symptoms.
Trajectory Analysis of Healthcare Utilization Before and After Major Surgery
Authors: Tarnasky Aaron , Ludwig Justin , Bilderback Andrew , Yoder Don , Schuster James , Kogan Jane , Hall Daniel 
Published: December 2023

Objective:
To characterize patterns of healthcare utilization before and after surgery and determine any association with pre-operative frailty.

Summary Background Data:
Frail patients experience worse post-operative outcomes and increased costs during the surgical encounter. Evidence is comparatively lacking for longer-term effects of frailty on post-operative healthcare utilization.

Methods:
Retrospective, longitudinal cohort analysis of adult patients undergoing any elective surgical procedure following pre-operative frailty assessment with the Risk Analysis Index (RAI) from 02/2016-12/2020 at a large integrated healthcare delivery and financing system. Group-based trajectory modeling of claims data estimated distinct clusters of patients with discrete utilization trajectories. Multivariable regression predicted membership in trajectories of interest using preoperative characteristics, including frailty.

Results:
Among 29,067 surgical encounters, four distinct utilization trajectories emerged in longitudinal data from the 12 months before and after surgery. All cases exhibited a surge in utilization during the surgical month, after which most patients returned to “low” [25,473 (87.6%)], “medium” [1,403 (4.8%)], or “high” [528 (1.8%)] baseline utilization states established before surgery. The fourth trajectory identified 1,663 (5.7%) cases where surgery occasioned a transition from “low” utilization before surgery to “high” utilization afterward. RAI score alone did not effectively predict membership in this transition group, but a multivariable model with other preoperative variables was effective (c=0.859, max re-scaled R-squared 0.264).

Conclusions and Relevance:
Surgery occasions the transition from low to high healthcare utilization for a substantial subgroup of surgical patients. Multivariable modeling may effectively discriminate this utilization trajectory, suggesting an opportunity to tailor care processes for these patients.
Drug-Coated Balloon Versus Drug-Eluting Stent for Treating De Novo Large Vessel Coronary Artery Disease: A Systematic Review and Meta-Analysis of 13 Studies Involving 2,888 Patients
Authors: Caminiti Rodolfo , Vizzari Giampiero , Ielasi Alfonso , Vetta Giampaolo , Parlavecchio Antonio , Della Rocca Domenico Giovanni , Montonati Carolina , Pellegrini Dario , Pellicano Mariano , Tespili Maurizio , Micari Antonio 
Published: December 2023

AbstractIntroductionDrug-coated balloon (DCB) is an established treatment option for in-stent restenosis and small vessel, de novo, coronary artery disease (CAD). Although the use of this tool is increasing in everyday practice, little is known about its performance in the treatment of de novo, large vessel CAD (LV-CAD). A systematic review and meta-analysis were conducted to evaluate the efficacy and safety of DCB versus drug-eluting stent (DES) in this setting.MethodsA comprehensive literature search was performed including Medline, Embase and Cochrane electronic databases up to October 24th2023, for studies which compared efficacy and safety of DCB versus DES in the treatment of de novo lesions in large vessels (≥ 2.5 mm), reporting at least one clinical outcome of interest (PROSPERO ID: CRD42023470417). The outcomes analysed were cardiovascular death (CVD), myocardial infarction (MI), target lesion revascularization (TLR), all cause death (ACD) and late lumen loss (LLL) at follow-up. The effect size was estimated using a random-effect model as risk ratio (RR) and mean difference (MD) and relative 95% confidence interval (CI).ResultsA total of 13 studies (6 randomized controlled trials and 7 observational studies) involving 2,888 patients (DCB n=1,334; DES n=1,533) with de novo LV-CAD were included in this meta-analysis following our inclusion criteria. A DCB-only strategy was non inferior to percutaneous coronary intervention (PCI) with DES in terms of CVD (RR 0.49; 95% CI [0.23 - 1.03]; p=0.06), MI (RR 0.48; 95% CI [0.16 - 1.45]; p=0.89), TLR (RR 0.73; 95% CI [0.40 - 1.34]; p=0.32), ACD (RR 0.78; 95% CI [0.57 - 1.07]; p=0.12) and LLL (MD −0.14; 95% CI [−0.30 - 0.02]; p=0.18) at follow-up.ConclusionOur meta-analysis showed that DCB PCI might provide a promising option for the management of selected, de novo LV-CAD compared to DES. However, more focused RCTs are needed to further prove the benefits of a “metal free” strategy in this subset of CAD.
Molecular Characterization of the Sea Lamprey Retina Illuminates the Evolutionary Origin of Retinal Cell Types
Authors: Wang Junqiang , Zhang Lin , Cavallini Martina , Pahlevan Ali , Sun Junwei , Morshedian Ala , Fain Gordon L. , Sampath Alapakkam P. , Peng Yi-Rong 
Published: December 2023

AbstractThe lamprey, a primitive jawless vertebrate whose ancestors diverged from all other vertebrates over 500 million years ago, offers a unique window into the primordial formation of the retina. Using single-cell RNA-sequencing, we characterized retinal cell types in lamprey and compared their molecular differentiation and regulatory networks with those in mouse and other jawed vertebrates. Our analysis revealed six cell classes and 74 distinct cell types. We discovered multiple conserved cell types shared between jawless and jawed lineages, including notably rods and cones, ON and OFF bipolar cells, and starburst amacrine cells. The conservation of these cell types indicates their emergence early in vertebrate evolution, highlighting the primal designs of retinal circuits for the rod pathway, ON-OFF discrimination, and direction selectivity. In contrast to this evidence for conservation, the pathways of diversification for amacrine cells and retinal ganglion cells appear to have distinctly diverged between the two lineages. Furthermore, we inferred master regulators in specifying retinal cell classes in both lamprey and macaque and identified common regulatory elements across species, underscoring the ancestral nature of the molecular origins governing retinal cell classes. Altogether, our characterization of the lamprey retina illuminates the evolutionary origin of visual processing in the retina.
Transcriptional complexity in the insect central complex: single nuclei RNA-sequencing of adult brain neurons derived from type 2 neuroblasts
Authors: Epiney Derek , Morales Chaya Gonzalo N , Dillon Noah R , Lai Sen-Lin , Doe Chris Q. 
Published: December 2023

AbstractIn both invertebrates such asDrosophilaand vertebrates such as mouse or human, the brain contains the most diverse population of cell types of any tissue. It is generally accepted that transcriptional diversity is an early step in generating neuronal and glial diversity, followed by the establishment of a unique gene expression profile that determines morphology, connectivity, and function. InDrosophila, there are two types of neural stem cells, called Type 1 (T1) and Type 2 (T2) neuroblasts. In contrast to T1 neuroblasts, T2 neuroblasts generate intermediate neural progenitors (INPs) that expand the number and diversity of cell types. The diversity of T2-derived neurons contributes a large portion of the central complex (CX), a conserved brain region that plays a role in sensorimotor integration. Recent work has revealed much of the connectome of the CX, but how this connectome is assembled remains unclear. Mapping the transcriptional diversity of neurons derived from T2 neuroblasts is a necessary step in linking transcriptional profile to the assembly of the adult brain. Here we perform single nuclei RNA sequencing of T2 neuroblast-derived adult neurons and glia. We identify clusters containing all known classes of glia, clusters that are male/female enriched, and 161 neuron-specific clusters. We map neurotransmitter and neuropeptide expression and identify unique transcription factor combinatorial codes for each cluster (presumptive neuron subtype). This is a necessary step that directs functional studies to determine whether each transcription factor combinatorial code specifies a distinct neuron type within the CX. We map several columnar neuron subtypes to distinct clusters and identify two neuronal classes (NPF+ and AstA+) that both map to two closely related clusters. Our data support the hypothesis that each transcriptional cluster represents one or a few closely related neuron subtypes.
Effectiveness and durability of mRNA-1273 BA.4/BA.5 bivalent vaccine (mRNA-1273.222) against SARS-CoV-2 BA.4/BA.5 and XBB sublineages
Authors: Ackerson Bradley K. , Bruxvoort Katia J. , Qian Lei , Sy Lina S. , Qiu Sijia , Tubert Julia E. , Lee Gina S. , Ku Jennifer H. , Florea Ana , Luo Yi , Bathala Radha , Stern Julie , Choi Soon K. , Takhar Harpreet S. , Aragones Michael , Marks Morgan A. , Anderson Evan J. , Zhou Cindy Ke , Sun Tianyu , Talarico Carla A. , Tseng Hung Fu 
Published: December 2023

AbstractBackgroundEmerging SARS-CoV-2 sublineages continue to cause serious COVID-19 disease, but most individuals have not received COVID-19 vaccine for >1 year. Assessment of long-term effectiveness of bivalent COVID-19 vaccines against circulating sublineages is important to inform the potential need for vaccination with updated vaccines.MethodsIn this test-negative study at Kaiser Permanente Southern California, sequencing-confirmed BA.4/BA.5- or XBB-related SARS-CoV-2-positive cases during 9/1/2022-6/30/2023 were matched 1:3 to SARS-CoV-2-negative controls. We assessed mRNA-1273 bivalent relative (rVE) and absolute vaccine effectiveness (VE) compared to ≥2 or 0 doses of original monovalent vaccine, respectively. Outcomes were BA.4/BA.5- or XBB-related infection, emergency department/urgent care (ED/UC) encounters, and hospitalization.ResultsThe rVE analysis included 20,966 cases and 62,898 controls. rVE (95%CI) against BA.4/BA.5 at 14-60 days and 121-180 days was 52.7% (46.9-57.8%) and 35.5% (-2.8%-59.5%) for infection, and 59.3% (49.7-67.0%) and 33.2% (-28.2-68.0%) for ED/UC encounters. For BA.4/BA.5-related hospitalizations, rVE was 71.3% (44.9-85.1%) and 52.0% (-1.2-77.3%) at 14-60 days and 61-120 days, respectively. rVE against XBB at 14-60 days and 121-180 days, was 48.8% (33.4-60.7%) and -3.9% (-18.1-11.3%) for infection, 70.7% (52.4-82.0%) and 15.7% (-6.0-33.2%) for ED/UC encounters, and 87.9% (43.8-97.4%) and 57.1% (17.0-77.8%) for hospitalization. Results for VE and subgroup analyses (age, immunocompromise, and previous SARS-CoV-2 infection) were similar to rVE analyses.ConclusionsrVE of mRNA-1273 bivalent vaccine against BA.4/BA.5 and XBB infections, ED/UC encounters, and hospitalizations waned over time. Periodic adjustment of vaccines to target emerging variants and revaccination may be important in reducing COVID-19 morbidity and mortality.SummarymRNA-1273 BA.4/BA.5 bivalent vaccine effectiveness against infection and hospitalization with BA.4/BA.5-related and XBB-related sublineages waned over time. Periodic vaccination with vaccines reflecting circulating variants may reduce SARS-CoV-2 associated morbidity and mortality.
Enhancing Therapeutic Insulin Transport from Macroencapsulated Islets Using Sub-Minute Pressure at Physiological Levels
Authors: Thomson Ella A. , Lee Sooyeon , Xu Haixia , Moeller Hannah , Sands Joanna , Lal Rayhan A. , Annes Justin P. , Poon Ada S. Y. 
Published: December 2023

AbstractCadaveric islet and stem cell-derived transplantations hold promise as treatments for type 1 diabetes. To tackle the issue of immunocompatibility, numerous cellular macroencapsulation techniques have been developed that utilize diffusion to transport insulin across an immunoisolating barrier. However, despite several devices progressing to human clinical trials, none have successfully managed to attain physiologic glucose control or insulin independence. Based on empirical evidence, macroencapsulation methods with multilayered, high islet surface density are incompatible with homeostatic, on-demand insulin delivery and physiologic glucose regulation, when reliant solely on diffusion. An additional driving force is essential to overcome the distance limit of diffusion. In this study, we present both theoretical proof and experimental validation that applying pressure at levels comparable to physiological diastolic blood pressure significantly enhances insulin flux across immunoisolation membranes—increasing it by nearly three orders of magnitude. This significant enhancement in transport rate allows for precise, sub-minute regulation of both bolus and basal insulin delivery. By incorporating this technique with a pump-based extravascular system, we demonstrate the ability to rapidly reduce glucose levels in diabetic rodent models, effectively replicating the timescale and therapeutic effect of subcutaneous insulin injection or infusion. This advance provides a potential path towards achieving insulin independence with islet macroencapsulation.One Sentence SummaryTowards improved glucose control, applying sub-minute pressure at physiological levels enhances therapeutic insulin transport from macroencapsulated islets.
In SilicoEvaluation of Cell Therapy in Acute versus Chronic Infarction: Role of Automaticity, Heterogeneity and Purkinje in Human
Authors: Riebel Leto Luana , Wang Zhinuo Jenny , Martinez-Navarro Hector , Trovato Cristian , Camps Julia , Berg Lucas Arantes , Zhou Xin , Doste Ruben , Oliveira Rafael Sachetto , Weber dos Santos Rodrigo , Biasetti Jacopo , Rodriguez Blanca 
Published: December 2023

AbstractHuman-based modelling and simulation offer an ideal testbed for novel medical therapies to guide experimental and clinical studies. Myocardial infarction (MI) is a common cause of heart failure and mortality, for which novel therapies are urgently needed. Although cell therapy offers promise, electrophysiological heterogeneity raises pro-arrhythmic safety concerns, where underlying complex spatio-temporal dynamics cannot be investigated experimentally. After demonstrating credibility of the modelling and simulation framework, we investigate cell therapy in acute versus chronic MI, and the role of cell heterogeneity, scar size and the Purkinje system.Simulations agreed with experimental and clinical recordings from ionic to ECG dynamics in acute and chronic infarction. Following cell delivery, spontaneous beats were facilitated by heterogeneity in cell populations, chronic MI due to tissue depolarisation, and slow sinus rhythm. Subsequent re-entrant arrhythmias occurred, in some instances with Purkinje involvement, and their susceptibility was enhanced by impaired Purkinje-myocardium coupling, large scars, and acute infarction.We conclude that homogeneity in injected cell populations minimises their spontaneous beating, which is enhanced by chronic MI, whereas a healthy Purkinje-myocardium coupling is key to prevent subsequent re-entrant arrhythmias, particularly for large scars.
Forest demography and biomass accumulation rates are associated with transient mean tree size vs density scaling relations
Authors: Yu Kailiang , Chen Han Y.H. , Gessler Arthur , Pugh Thomas A.M. , Searle Eric B. , Allen Robert B. , Pretzsch Hans , Ciais Philippe , Phillips Oliver L. , Brienen Roel J.W. , Chu Chengjin , Xie Shubin , Ballantyne Ashley P. 
Published: December 2023

AbstractLinking individual and stand-level dynamics during forest development reveals a scaling relationship between mean tree size and tree density in forest stands, which integrates forest structure and function. However, the nature of this so-called scaling law and its variation across broad spatial scales remains unquantified and its linkage with forest demographic processes and carbon dynamics remains elusive. Here we develop a theoretical framework and compile a broad-scale dataset of long-term sample forest stands (n = 1433) from largely undisturbed forests to examine the association of temporal mean tree size vs density scaling trajectories (slopes) with biomass accumulation rates and the sensitivity of scaling slopes to environmental and demographic drivers. The results empirically demonstrate a large variation of scaling slopes, ranging from -4 to -0.2, across forest stands in tropical, temperate and boreal forest biomes. Steeper scaling slopes are associated with higher rates of biomass accumulation, resulting from a lower offset of forest growth by biomass loss from mortality. In North America, scaling slopes are positively correlated with forest stand age and rainfall seasonality, thus suggesting a higher rate of biomass accumulation in younger forests with lower rainfall seasonality. These results demonstrate the strong association of the transient mean tree size vs density scaling trajectories with forest demography and biomass accumulation rates, thus highlighting the promise of leveraging forest structure properties to predict forest demography, carbon fluxes and dynamics at broad spatial scales.Significance StatementMean tree size vs density scaling relationships are thought to predict forest function at broad spatial scales. Here we develop a theoretical framework based upon demographic processes and empirical evidence from forest inventory data to demonstrate a strong association of the transient mean tree size and density scaling trajectories (slopes) with forest demography and biomass accumulation rates. This strong association is pervasive across forest biomes and suggests a negative relationship between scaling slope and biomass accumulation rate (resource availability). Our results highlight the promise of leveraging forest structure (i.e., inferred from high resolution remote sensing data or fused into size-structured demographic models) to evaluate forest demography, carbon fluxes and dynamics at broad spatial scales.
Function-associated scRNA-seq on single lung cancer organoids unravels the immune landscape of tumor parenchyma
Authors: Liu Chang , Li Kaiyi , Sui Xizhao , Zhao Tian , Zhang Ting , Chen Zhongyao , Wu Hainan , Li Chao , Li Hao , Yang Fan , Liu Zhidong , Lu You-Yong , Wang Jun , Chen Xiaofang , Liu Peng 
Published: December 2023

AbstractIn vitro models coupled with multimodal approaches are urgently needed to decipher the local tumor immune microenvironment (TIME) owing to the heterogeneous nature of immune cells and their diverse spatial distributions. Here we generate primary lung cancer organoids (pLCOs) by isolating the tumor cell clusters, including the infiltrated immune cells, from dissected lung cancer samples. A FascRNA-seq platform allowing both phenotypic evaluation and the scRNA-seq of all the single cells in an organoid was developed to dissect the TIME in individual pLCOs. Our analysis on 171 individual pLCOs derived from 7 patients revealed that pLCOs retained the fundamental features as well as intra-tumor heterogeneity of local TIME in the parenchyma of parental tumor tissues, providing a series of models with consistent genetic background but various TIME. Linking the single cell transcriptome data of individual pLCOs with their responses to ICB allowed us to confirm the pivotal role of CD8+Ts in ICB induced anti-tumor immunity, to identify the potential tumor-reactive T cells with a set of 10 genes, and to unravel the factors regulating T cell activity.