bluuebunny/crossref_metadata_2025_split huggingface dataset:
Angiography-Based Fractional Flow Reserve: State of the Art
Authors: Scoccia Alessandra , Tomaniak Mariusz , Neleman Tara , Groenland Frederik T. W. , Plantes Annemieke C. Ziedses des , Daemen Joost 
Published: April 2022

Abstract
Purpose of Review
Three-dimensional quantitative coronary angiography-based methods of fractional flow reserve (FFR) derivation have emerged as an appealing alternative to conventional pressure-wire-based physiological lesion assessment and have the potential to further extend the use of physiology in general. Here, we summarize the current evidence related to angiography-based FFR and perspectives on future developments.

Recent Findings
Growing evidence suggests good diagnostic performance of angiography-based FFR measurements, both in chronic and acute coronary syndromes, as well as in specific lesion subsets, such as long and calcified lesions, left main coronary stenosis, and bifurcations. More recently, promising results on the superiority of angiography-based FFR as compared to angiography-guided PCI have been published.

Summary
Currently available angiography -FFR indices proved to be an excellent alternative to invasive pressure wire-based FFR. Dedicated prospective outcome data comparing these indices to routine guideline recommended PCI including the use of FFR are eagerly awaited.
Early Life Social Stress Causes Sex- and Region-Dependent Dopaminergic Changes that Are Prevented by Minocycline
Authors: Catale Clarissa , Lo Iacono Luisa , Martini Alessandro , Heil Constantin , Guatteo Ezia , Mercuri Nicola Biagio , Viscomi Maria Teresa , Palacios Daniela , Carola Valeria 
Published: April 2022

Abstract
Early life stress (ELS) is known to modify trajectories of brain dopaminergic development, but the mechanisms underlying have not been determined. ELS perturbs immune system and microglia reactivity, and inflammation and microglia influence dopaminergic transmission and development. Whether microglia mediate the effects of ELS on dopamine (DA) system development is still unknown. We explored the effects of repeated early social stress on development of the dopaminergic system in male and female mice through histological, electrophysiological, and transcriptomic analyses. Furthermore, we tested whether these effects could be mediated by ELS-induced altered microglia/immune activity through a pharmacological approach. We found that social stress in early life altered DA neurons morphology, reduced dopamine transporter (DAT) and tyrosine hydroxylase expression, and lowered DAT-mediated currents in the ventral tegmental area but not substantia nigra of male mice only. Notably, stress-induced DA alterations were prevented by minocycline, an inhibitor of microglia activation. Transcriptome analysis in the developing male ventral tegmental area revealed that ELS caused downregulation of dopaminergic transmission and alteration in hormonal and peptide signaling pathways. Results from this study offer new insight into the mechanisms of stress response and altered brain dopaminergic maturation after ELS, providing evidence of neuroimmune interaction, sex differences, and regional specificity.
Novel Approaches Guiding the Future of Spinal Biologics for Bone Regeneration
Authors: Phan Eileen N. , Hsu Wellington K. 
Published: April 2022

Abstract
Purpose of Review
Despite the continued growth of spine fusion procedures, the ideal material for bone regeneration remains unclear. Current bone graft substitutes and extenders in use such as exogenous BMP-2 or demineralized bone matrix and hydroxyapatite either have serious complications associated with use or lead to clinically significant rates of non-union. The introduction of nanotechnology and 3D printing to regenerative medicine facilitates the development of safer and more efficacious bone regenerative scaffolds that present solutions to these problems. Many researchers in orthopedics recognize the importance of lowering the dose of recombinant growth factors like BMP-2 to avoid the complications associated with its normal required supraphysiologic dosing to achieve high rates of fusion in spine surgery.

Recent Findings
Recent iterations of bioactive scaffolds have moved towards peptide amphiphiles that bind endogenous osteoinductive growth factor sources at the site of implantation. These molecules have been shown to provide a highly fluid, natural mimetic of natural extracellular matrix to achieve 100% fusion rates at 10–100 times lower doses of BMP-2 relative to controls in pre-clinical animal posterolateral fusion models. Alternative approaches to bone regeneration include the combination of existing natural growth factor sources like human bone combined with bioactive, biocompatible components like hydroxyapatite using 3D-printing technologies. Their elastomeric, 3D-printed scaffolds demonstrate an optimal safety profile and high rates of fusion (~92%) in the rat posterolateral fusion model.

Summary
Bioactive peptide amphiphiles and developments in 3D printing offer the promising future of a recombinant growth factor- free bone graft substitute with similar efficacy but improved safety profiles compared to existing bone graft substitutes.
Validation of a nuclear grading system for resected stage I–IIIA, high-risk, node-negative invasive breast carcinoma in the N·SAS-BC 01 trial
Authors: Tsuda Hitoshi , Kurosumi Masafumi , Akiyama Futoshi , Ohno Shinji , Saji Shigehira , Masuda Norikazu , Shimomura Akihiko , Sato Nobuaki , Takao Shintaro , Ohsumi Shozo , Tokuda Yutaka , Inaji Hideo , Watanabe Toru 
Published: April 2022

Abstract
Background
This retrospective observational study validated nuclear grading criteria developed to identify a high-risk group with recurrence rate ≥20–30% and local pathology diagnosis used in a previous multi-institutional randomized N·SAS-BC 01 trial, where the efficacy of adjuvant chemotherapy regimens was evaluated in 733 high-risk node-negative invasive breast cancer patients.

Methods
Of 545 patients with long-term follow-up data (median 12.1 years), pathology slides, and local pathology diagnosis, 530 eligible patients were subjected to central pathology review (CPR) for histological type and nuclear grade (NG). Concordance in NGs was compared with local diagnosis. The 10/15-year recurrence-free survival (RFS) and overall survival (OS) rates stratified by NG and histological type were calculated.

Results
Local diagnoses were invasive ductal carcinoma (IDC)-NG2, IDC-NG3, invasive lobular carcinoma (ILC), and metaplastic carcinoma (MC) in 158/327/38/7 patients, respectively. The 10/15-year RFS rates were 87.2/82.6% for IDC-NG2 and 81.8/75.0% for IDC-NG3 (p = 0.061), and OS rates were 95.0/92.8% for IDC-NG2 and 90.8/85.7% for IDC-NG3 (p = 0.042). CPR graded 485 locally diagnosed IDCs as IDC-NG1/NG2/NG3/unknown in 98/116/267/4 patients, respectively. No significant difference was found among survival curves for the three NG groups. Although the agreement level between local and CPR diagnoses was low (κ = 0.311), both diagnoses identified a patient group with a 15-year recurrence rate ≥ 20%. The 10/15-year RFS rates were 79.4/63.5% for ILC and 68.6%/unknown for MC.

Conclusions
The N·SAS grading system identified a patient group with high-risk node-negative invasive breast cancer, suggesting that local diagnosis was performed efficiently in the N·SAS-BC 01 trial.
Trial registration number: UMIN000022571.
Date of registration: June 1, 2016.
Declining morphological diversity in snakefly larvae during last 100 million years
Authors: Haug Joachim T. , Engel Michael S. , Mendes dos Santos Patrick , Haug Gideon T. , Müller Patrick , Haug Carolin 
Published: April 2022

AbstractRaphidioptera, the group of snakeflies, is a rather species-poor in-group of Holometabola. Yet, fossils of snakeflies indicate that the group was more diverse in the past. Here we compare the morphological diversity of snakefly larvae over time. Snakefly larvae are well represented in Cretaceous and Eocene ambers facilitating such a comparison. We used measurements of discrete dimensions as a basis for comparison. This reveals a larger diversity of snakefly larvae in the Cretaceous, especially in relation to head shapes and morphology of the antennae, which were much more variable. In particular, some Cretaceous larvae possessed greatly elongated head capsules and uniquely long and prominent antennae, unparalleled among modern forms. Already by the Eocene, snakefly larvae were less variable than those of the Cretaceous, although some still possessed longer antennae than modern-day larvae. The loss of morphological diversity supports the already well-established loss of taxonomic diversity in the group across time. Quite likely, this also indicates a loss of ecological diversity. These results are comparable to losses in different lineages of the closely related group Neuroptera.
EDP-mitotane in children: reassuring evidence of reversible side-effects and neurotoxicity
Authors: Steenaard Rebecca V. , Rutjens Marieke , Ettaieb Madeleine H. T. , van Noesel Max M. , Haak Harm R. 
Published: April 2022

AbstractAdrenocortical carcinoma affects one in 5 million children each year. Since prognosis for children older than 4 years is limited, clinicians often choose aggressive treatment with etoposide, doxorubicin, cisplatin (EDP) and mitotane after resection. However, little is known about the impact of EDP-mitotane in children. We provide an overview of case-reports and case series listing side-effects and neurotoxicity of EDP-mitotane in children. Fourteen studies were identified describing a range of gastro-intestinal, endocrine, developmental and neuropsychological side-effects. Neurotoxicity included motor- and speech delay, decreased concentration and lower school performance. These side-effects appear to be reversible after mitotane discontinuation. We have added our own experience with a 10 year old girl with advanced adrenocortical carcinoma treated with EDP and 2 years of mitotane after irradical resection. She developed an impactful, but reversible, decrease in cognitive development measured by a standardized neuropsychological assessment before, during and after mitotane therapy. This decrease was mostly measurable in terms of decreased processing speed and concentration and a significant drop in school performance. Combined with fatigue and insecurity, this caused problems in short-term memory and the need to change her school type. In conclusion, EDP-mitotane is associated with several side-effects including neurotoxicity in pediatric cases, all reversible after mitotane discontinuation.
T cell differentiation protein 2 facilitates cell proliferation by enhancing mTOR-mediated ribosome biogenesis in non-small cell lung cancer
Authors: Lian Zhenying , Yan Xingyu , Diao Yutao , Cui Dayong , Liu Hongyan 
Published: April 2022

AbstractDysregulation of T cell differentiation protein 2 (MAL2) has been observed in multiple cancers, but its exact role in lung cancer is poorly understood. Here we report a role of MAL2 in accelerating cell proliferation in non-small cell lung cancer (NSCLC). MAL2 expression enhances cell proliferation in both cell and nude mouse models. Mechanistically, overexpression of MAL2 results in the hyper-activation of the MAPK/mTOR signaling pathway in NSCLC cells which leads to active ribosome biogenesis. Importantly, pharmacological inhibition of mTOR or MEK lowered the abundance of PCNA, a marker of tumor cell proliferation, and subsequently suppressed ribosome biogenesis, cell growth and xenograft growth in mouse model. MAL2 upregulation in clinical tumors is also linked to worse prognosis. Overall our data reveal that MAL2 is a potential diagnostic biomarker and targeting the MAL2/MAPK/mTOR signaling pathway may improve therapeutic strategy and efficacy for this subset of NSCLC patients.
Contrasting phylogeographic patterns of intertidal mites (Acari, Oribatida) along the South African shoreline
Authors: Pfingstl Tobias , Wagner Maximilian , Baumann Julia , Neethling Jan Andries , Bardel-Kahr Iris , Hugo-Coetzee Elizabeth A. 
Published: April 2022

AbstractThe South African coast is known to harbor four different species of intertidal oribatid mites and their distribution strongly correlates with marine ecoregions. Relatively little is known about the dispersal of these organisms and how populations of different locations are connected. To test dispersal abilities and connectivity of these South African species, we performed a morphometric and molecular genetic study. COI gene sequences of two of the widely distributed South African intertidal oribatid mite species revealed clearly contrasting patterns. Halozetes capensis, which occurs in the Agulhas Ecoregion, shows distinct genetic structuring, whereas Fortuynia elamellata micromorpha, which is distributed in the Natal Ecoregion, exhibits gene flow between all populations. The paleoenvironmental history and specific ocean current pattern are suggested to be responsible for these patterns. During the last glacial maximum, the colder climate and the weakening of the Agulhas Current possibly resulted in a bottleneck in the warm-adapted F. e. micromorpha populations, but the subsequent global warming allowed the populations to expand again. The cold-adapted H. capensis populations, on the other hand, experienced no dramatic changes during this period and thus could persist in the Agulhas Ecoregion. Considering transport on ocean currents, the Agulhas Current could be further responsible for the connectivity between the Fortuynia populations. But the deflection of this current in the Agulhas Ecoregion could support the isolation of Halozetes populations. The concomitant morphometric study demonstrated morphological homogeneity among populations of Fortuynia and thus confirms strong connectivity. The Halozetes populations, on the other hand, form two different morphological groups not reflecting geography.
Introducing an Austrian backpack in Spain
Authors: Sousa João Brogueira de , Díaz-Saavedra Julián , Marimon Ramon 
Published: April 2022

AbstractIn an overlapping generations economy with incomplete insurance markets, the introduction of an employment fund—akin to the one introduced in Austria in 2003, also known as ‘Austrian backpack’—can enhance production efficiency and social welfare. It complements the two classical systems of public insurance: pay-as-you-go (PAYG) pensions and unemployment insurance (UI). We show this in a calibrated dynamic general equilibrium model with heterogeneous agents of the Spanish economy in 2018. A ‘backpack’ (BP) employment fund is an individual (across jobs) transferable fund, which earns a market interest rate as a return and is financed with a payroll tax (a BP tax). The worker can use the fund while unemployed or retired. Upon retirement, backpack savings can be converted into an (actuarially fair) retirement pension. To complement the existing PAYG pension and UI systems with a welfare maximizing 6% BP tax would raise welfare by 0.96% of average consumption at the new steady state, if we model Spain as an open economy. As a closed economy, there are important general equilibrium effects, and as a result, the social value of introducing the backpack is substantially greater: 16.14%, with a BP tax of 18%. In both economies, the annuity retirement option is an important component of the welfare gains.
The fractional-order Lorenz-type systems: A review
Authors: Petráš Ivo 
Published: April 2022

Abstract
This paper deals with a survey of Lorenz-type systems. For the first time, a new classification of the fractional-order Lorenz-type systems was introduced. Several chaotic systems, as particular cases of the new general form, which belong to large Lorenz family, are presented together with equilibria, eigenvalues as well as attractors of these systems in 3-dimensional state space, respectively.
Monte Carlo method for fractional-order differentiation
Authors: Leonenko Nikolai , Podlubny Igor 
Published: April 2022

Abstract
In this work the Monte Carlo method is introduced for numerical evaluation of fractional-order derivatives. A general framework for using this method is presented and illustrated by several examples. The proposed method can be used for numerical evaluation of the Grünwald-Letnikov fractional derivatives, the Riemann-Liouville fractional derivatives, and also of the Caputo fractional derivatives, when they are equivalent to the Riemann-Liouville derivatives. The proposed method can be enhanced using standard approaches for the classic Monte Carlo method, and it also allows easy parallelization, which means that it is of high potential for applications of the fractional calculus.
Sodium-ion battery from sea salt: a review
Authors: Nurohmah Anisa Raditya , Nisa Shofirul Sholikhatun , Stulasti Khikmah Nur Rikhy , Yudha Cornelius Satria , Suci Windhu Griyasti , Aliwarga Kiwi , Widiyandari Hendri , Purwanto Agus 
Published: April 2022

AbstractThe electrical energy storage is important right now, because it is influenced by increasing human energy needs, and the battery is a storage energy that is being developed simultaneously. Furthermore, it is planned to switch the lithium-ion batteries with the sodium-ion batteries and the abundance of the sodium element and its economical price compared to lithium is the main point. The main components anode and cathode have significant effect on the sodium battery performance. This review briefly describes the components of the sodium battery, including the anode, cathode, electrolyte, binder, and separator, and the sources of sodium raw material is the most important in material synthesis or installation. Sea salt or NaCl has potential ability as a raw material for sodium battery cathodes, and the usage of sea salt in the cathode synthesis process reduces production costs, because the salt is very abundant and environmentally friendly as well. When a cathode using a source of Na2CO3, which was synthesized independently from NaCl can save about 16.66% after being calculated and anode with sodium metal when synthesized independently with NaCl can save about 98% after being calculated, because sodium metal is classified as expensive matter.
Understanding current UK practice for the incidental identification of vertebral fragility fractures from CT scans: an expert elicitation study
Authors: Dalal Garima , Bromiley Paul A. , Kariki Eleni P. , Luetchens Shawn , Cootes Timothy F. , Payne Katherine 
Published: April 2022

Abstract
Background
There is an emerging interest in using automated approaches to enable the incidental identification of vertebral fragility fractures (VFFs) on existing medical images visualising the spine.

Aim
To quantify values, and the degree of uncertainty associated with them, for the incidental identification of VFFs from computed tomography (CT) scans in current practice.

Methods
An expert elicitation exercise was conducted to generate point estimates and measures of uncertainty for four values representing the probability of: VFF being correctly reported by the radiologist; the absence of VFF being correctly assessed by the radiologist; being referred for management when a VFF is identified; having a dual-energy X-ray absorptiometry (DXA) scan after general practitioner (GP) referral. Data from a sample of seven experts in the diagnosis and management of people with VFFs were pooled using mathematical aggregation.

Results
The estimated mean values for each probability parameter were: VFF being correctly reported by the radiologist = 0.25 (standard deviation (SD): 0.21); absence of VFF being correctly assessed by the radiologist = 0.89 (0.10); being referred for management when a VFF is identified by the radiologist = 0.15 (0.12); having a DXA scan after GP referral = 0.66 (0.28).

Discussion
These estimates could be used to facilitate the subsequent early economic evaluation of potential new approaches to improve the health outcomes of people with VFFs.

Conclusion
In the absence of epidemiological studies, this study produced point estimates and measures of uncertainty for key parameters needed to describe current pathways for the incidental diagnosis of VFFs.
Comorbidity and osteoporotic fracture: approach through predictive modeling techniques using the OSTEOMED registry
Authors: Coco Martín María Begoña , Leal Vega Luis , Blázquez Cabrera José Antonio , Navarro Amalia , Moro María Jesús , Arranz García Francisca , Amérigo María José , Sosa Henríquez Manuel , Vázquez María Ángeles , Montoya María José , Díaz Curiel Manuel , Olmos José Manuel , Pérez Castrillón José Luis ,   OSTEOMED Group, Filgueira Rubio José , Sánchez Molini Pilar , Aguado Caballero José María , Armengol Sucarrats Dolors , Calero Bernal María Luz , de Escalante Yanguas Begoña , Hernández de Sosa Nerea , Hernández José Luis , Jareño Chaumel Julia , Miranda García María José , Giner García Mercedes , Miranda Díaz Cristina , Cotos Canca Rafael , Cobeta García Juan Carlos , Rodero Hernández Francisco Javier , Tirado Miranda Raimundo 
Published: April 2022

Abstract
Purpose
To examine the response to anti-osteoporotic treatment, considered as incident fragility fractures after a minimum follow-up of 1 year, according to sex, age, and number of comorbidities of the patients.

Methods
For this retrospective observational study, data from baseline and follow-up visits on the number of comorbidities, prescribed anti-osteoporotic treatment and vertebral, humerus or hip fractures in 993 patients from the OSTEOMED registry were analyzed using logistic regression and an artificial network model.

Results
Logistic regression showed that the probability of reducing fractures for each anti-osteoporotic treatment considered was independent of sex, age, and the number of comorbidities, increasing significantly only in males taking vitamin D (OR = 7.918), patients without comorbidities taking vitamin D (OR = 4.197) and patients with ≥ 3 comorbidities taking calcium (OR = 9.412). Logistic regression correctly classified 96% of patients (Hosmer–Lemeshow = 0.492) compared with the artificial neural network model, which correctly classified 95% of patients (AUC = 0.6).

Conclusion
In general, sex, age and the number of comorbidities did not influence the likelihood that a given anti-osteoporotic treatment improved the risk of incident fragility fractures after 1 year, but this appeared to increase when patients had been treated with risedronate, strontium or teriparatide. The two models used classified patients similarly, but predicted differently in terms of the probability of improvement, with logistic regression being the better fit.
Seeing is Believing: Inclusion of Biomedical Scientist Educators as Observers on Clinical Rounds
Authors: Clay Alison , Velkey Matt , Andolsek Kathryn M. , Knudsen Nancy W. 
Published: April 2022

Abstract
Increasingly, medical school curricula seek to integrate the biomedical and clinical sciences. Inclusion of the basic sciences into the clinical curricula is less robust than including clinical content early in medical school. We describe inclusion of biomedical scientists on patient care rounds to increase the visibility of biomedical sciences, to nurture relationships between clinicians and biomedical scientists, and to identify additional opportunities for integration throughout medical school.