bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preclinical to clinical translation for intervertebral disc repair: Effects of species‐specific scale, metabolism, and matrix synthesis rates on cell‐based regeneration
Authors: McDonnell Emily E. , Wilson Niamh , Barcellona Marcos N. , Ní Néill Tara , Bagnall Jessica , Brama Pieter A. J. , Cunniffe Gráinne M. , Darwish Stacey L. , Butler Joseph S. , Buckley Conor T. 
Published: September 2023

AbstractBackgroundA significant hurdle for potential cell‐based therapies is the subsequent survival and regenerative capacity of implanted cells. While many exciting developments have demonstrated promise preclinically, cell‐based therapies for intervertebral disc (IVD) degeneration fail to translate equivalent clinical efficacy.AimsThis work aims to ascertain the clinical relevance of both a small and large animal model by experimentally investigating and comparing these animal models to human from the perspective of anatomical scale and their cellular metabolic and regenerative potential.Materials and MethodsFirst, this work experimentally investigated species‐specific geometrical scale, native cell density, nutrient metabolism, and matrix synthesis rates for rat, goat, and human disc cells in a 3D microspheroid configuration. Second, these parameters were employed in silico to elucidate species‐specific nutrient microenvironments and predict differences in temporal regeneration between animal models.ResultsThis work presents in silico models which correlate favorably to preclinical literature in terms of the capabilities of animal regeneration and predict that compromised nutrition is not a significant challenge in small animal discs. On the contrary, it highlights a very fine clinical balance between an adequate cell dose for sufficient repair, through de novo matrix deposition, without exacerbating the human microenvironmental niche.DiscussionOverall, this work aims to provide a path towards understanding the effect of cell injection number on the nutrient microenvironment and the “time to regeneration” between preclinical animal models and the large human IVD. While these findings help to explain failed translation of promising preclinical data and the limited results emerging from clinical trials at present, they also enable the research field and clinicians to manage expectations on cell‐based regeneration.ConclusionUltimately, this work provides a platform to inform the design of clinical trials, and as computing power and software capabilities increase in the future, it is conceivable that generation of patient‐specific models could be used for patient assessment, as well as pre‐ and intraoperative planning.
Quantification of short‐term transformations of proglacial landforms in a temperate, debris‐charged glacial landsystem, Kvíárjökull, Iceland
Authors: Śledź Szymon , Ewertowski Marek W. , Evans David J. A. 
Published: September 2023

AbstractProglacial areas are dynamic landscapes and important indicators of geomorphic changes related to climate warming. Systematic and repeat surveys of landforms presently evolving on glacier forelands facilitate the quantification of rates of change and an improved understanding of the processes generating those changes. We report short‐term (2014–2022) transformations of the proglacial landscape in front of Kvíárjökull, SE Iceland, and place them in a longer‐term context of glacial landsystem evolution using aerial image archives since 1945. Short‐term quantification uses a time series of uncrewed aerial vehicle (UAV) surveys, processed utilizing a structure‐from‐motion (SfM) workflow, to produce digital elevation models (DEMs) and orthophoto mosaics. The land elements surveyed include a kame terrace staircase, an outwash plain, an ice‐cored hummocky moraine complex and ice‐cored hummocky terrain with discontinuous sinuous ridges, for which elevation and volumetric changes are quantified. The kame terraces between 2014 and 2022 and the outwash plain between 2016 and 2022 were mainly stable with, respectively, 87% and 85% of their surfaces showing no change. The ice‐cored hummocky terrain with discontinuous sinuous ridges underwent a volume loss of 64,632 m3 in 2016–2022, with a maximum surface lowering of ≤9 m. The most dynamic land element was the ice‐cored hummocky moraine complex, with transformations recorded for more than 87% of its area in 2014–2022; the surface was lowered by ≤23 m in some places, with a total volume loss of 365,773 m3. Our results confirm the ongoing degradation of ice‐cored moraine and outwash complexes at variable rates related to buried ice volume and age of deglaciation. The evolution of chaotic hummocky terrain from debris‐covered glacier ice, glacitectonic thrust masses, outwash fans/heads and complex englacial esker networks is an important modern analogue for informing palaeoglaciological reconstructions.
Phytoplankton as indicators of global warming?
Authors: Cloern James E. , Schraga Tara S. , Nejad Erica , Eddy Taylor 
Published: September 2023

AbstractTerrestrial plants are sensitive indicators of global warming because their annual cycles of growth and senescence are changing as warming proceeds. Single celled algae are distinct life forms capable of population bursts in any season, so there is uncertainty about phytoplankton phenology as a comparable indicator of global warming. We analyzed 4+ decades of monthly chlorophyll a measurements at two sites in San Francisco Bay and found abrupt shifts during summer months leading to a 48‐day advance in the annual pattern of chlorophyll‐a accumulation at one site and a 36‐day delay at the other. These large phenological changes were not associated with changing temperature, but they were associated with changes in top–down control by bivalve filter feeders as biological communities were restructured by (1) introduction of a non‐native clam, and (2) a shift in atmospheric forcing of the NE Pacific. This study illustrates that changes in phytoplankton phenology are not necessarily responses to or indicators of global warming. However, they can be indicators of human disturbances and natural climate oscillations having effects large enough to mask the effect of climate warming.
Technical note: Clinical evaluation of a newly released surface‐guided radiation therapy system on DIBH for left breast radiation therapy
Authors: Zhao Hui , Sarkar Vikren , Paxton Adam , Huang Y. Jessica , Haacke Christine , Price Ryan G. , Frances Su Fan‐Chi , Szegedi Martin , Rassiah Prema , Salter Bill 
Published: September 2023

AbstractBackgroundIt has been shown that a significant reduction of mean heart dose and left anterior descending artery (LAD) dose can be achieved through the use of DIBH for left breast radiation therapy. Surface‐guided DIBH has been widely adopted during the last decade, and there are mainly three commercially available SGRT systems. The reports of the performance of a newly released SGRT system for DIBH application are currently very limited.PurposeTo evaluate the clinical performance of a newly released SGRT system on DIBH for left breast radiation therapy.MethodsTwenty‐five left breast cancer patients treated with DIBH utilizing Varian's Identify system were included (total 493‐fraction treatments). Four aspects of the clinical performance were evaluated: Identify offsets of free breathing post patient setup from tattoos, Identify offsets during DIBH, Identify agreement with radiographic ports during DIBH, and DIBH reference surface re‐capture post patient shifts. The systematic and random errors of free breathing Identify offsets post patient setup were calculated for each patient, as well as for offsets during DIBH. Radiographic ports were taken when the patient's DIBH position was within the clinical tolerance of (± 0.3 cm, ± 30), and these were then compared with treatment field DRRs. If the ports showed that the patient alignment did not agree with the DRRs within 3 mm, a patient shift was performed. A new reference surface was captured and verification ports were taken.ResultsThe all‐patient average systematic and random errors of Identify offsets for free breathing were within (0.4 cm, 1.50) post tattoo setup. The maximum per‐patient systematic and random errors were (1.1 cm, 6.20) and (0.9 cm, 20), and the maximum amplitude of Identify offsets were (2.59 cm, 90). All 493‐fraction DIBH treatments were delivered and successfully guided by the Identify SGRT system. The systematic and random errors of Identify offsets for DIBH were within (0.2 cm, 2.30). Seven patients needed re‐captured surface references due to surface variation or position shifts based on the ports. All patient DIBH verification ports guided by Identify were approved by attending physicians.ConclusionThis evaluation showed that the Identify system performed effectively for surface‐guided patient setup and surface‐guided DIBH imaging and treatment delivery. The feature of color‐coded real‐time patient surface matching feedback facilitated the evaluation of the patient alignment accuracy and the adjustment of the patient position to match the reference.
Robust mixed electron‐photon radiation therapy planning for soft tissue sarcoma
Authors: Heng Veng Jean , Serban Monica , Renaud Marc‐André , Freeman Carolyn , Seuntjens Jan 
Published: September 2023

AbstractBackgroundMixed electron‐photon beam radiation therapy (MBRT) is an emerging technique in which external electron and photon beams are simultaneously optimized into a single treatment plan. MBRT exploits the steep dose falloff and high surface dose of electrons while maintaining target conformity by leveraging the sharp penumbra of photons.PurposeThis study investigates the dosimetric benefits of MBRT for soft tissue sarcoma (STS) patients.Material and methodsA retrospective cohort of 22 STS of the lower extremity treated with conventional photon‐based Volumetric Modulated Arc Therapy (VMAT) were replanned with MBRT. Both VMAT and MBRT treatments were planned on the Varian TrueBeam linac using the Millenium multi‐leaf collimator. No electron applicator, cutout or additional collimating devices were used for electron beams of MBRT plans. MBRT plans were optimized to use a combination of 6 MV photons and five electron energies (6, 9, 12, 16, 20 MeV) by a robust column generation algorithm. Electron beams in this study were planned at standard 100 cm source‐axis distance (SAD). The dose to the clinical target volume (CTV), bone, normal tissue strip and other organs‐at‐risk (OARs) were compared using a Wilcoxon signed‐rank test.ResultsAs part of the original VMAT treatment, tissue‐equivalent bolus was required in 10 of the 22 patients. MBRT plans did not require bolus by virtue of the higher electron entrance dose. CTV coverage by the prescription dose was found to be clinically equivalent between plans of either modality: (MBRT) = 97.9 ± 0.2% versus (VMAT) = 98.1 ± 0.6% (p=0.34). Evaluating the absolute paired difference between doses to OARs in MBRT and VMAT plans, we observed lower to normal tissue in MBRT plans by 14.9 ± 3.2% (). Similarly, to bone was found to be decreased by 8.2 ± 4.0% () of the bone volume.ConclusionFor STS with subcutaneous involvement, MBRT offers statistically significant sparing of OARs without sacrificing target coverage when compared to VMAT. MBRT plans are deliverable on conventional linacs without the use of electron applicators, shortened source‐to‐surface distance (SSD) or bolus. This study shows that MBRT is a logistically feasible technique with clear dosimetric benefits.
Cyanoacrylate Tissue Adhesives Compared With Sutures on Facial and Neck Wounds: A Meta‐analysis
Authors: Charoenlux Prapitphan , Utoomprurkporn Nattawan , Seresirikachorn Kachorn 
Published: September 2023

AbstractObjectiveTo compare the effectiveness between cyanoacrylate tissue adhesives (CTAs) and sutures for skin closure on the face and neck.Data SourcesEmbase, Medline, Scopus, Central, Web of Science.Review MethodsRandomized controlled trials comparing CTAs versus sutures for skin closure on the face and neck were included. Primary outcomes were cosmetic outcomes. Secondary outcomes were scar depth, scar width, pain, closure time, cost, and adverse events. Subgroup analyses were performed by wound locations, type of CTAs, type of sutures, age groups, and type of wounds. Physicians and patients evaluated the cosmetic outcomes.ResultsEighteen studies (1020 patients) were included. CTAs offered better cosmetic outcomes by Wound Registry Scale at ≤1 month (physician: mean difference [MD]: −1.50, 95% confidence interval, CI: −2.42 to −0.58). The cosmetic outcomes assessed by Visual Analog Scale were comparable at >1 to ≤3 months (physicians: standard mean difference [SMD], −0.01, 95% CI, −0.25 to 0.23, patients: SMD, −0.02, 95% CI, −0.84 to 0.79). The cosmetic outcomes by the Patient and Observer Scar Assessment Scale favored sutures at >3 to 12 months (physician: MD 4.26, 95% CI, 2.02‐6.50). Subgroup analyses revealed no differences. CTAs offered less scar depth, scar width, pain, closure time, and total cost of closure. Adverse events were similar.ConclusionBased on the wound healing process, the cosmetic outcomes exhibited a favorable inclination toward CTAs at <1 month while demonstrating comparable results between CTAs and sutures at >1 to ≤3 months. Subsequently, sutures exhibited superior cosmetic outcomes compared to CTAs at >3 to 12 months.
Single‐cell profiling identifies distinct hormonal, immunologic, and inflammatory signatures of endometriosis‐constituting cells
Authors: Shin Sun , Chung Youn‐Jee , Moon Seong Won , Choi Eun Ji , Kim Mee‐Ran , Chung Yeun‐Jun , Lee Sug Hyung 
Published: September 2023

AbstractEndometriosis consists of ectopic endometrial epithelial cells (EEECs) and ectopic endometrial stromal cells (EESCs) mixed with heterogeneous stromal cells. To address how endometriosis‐constituting cells are different from normal endometrium and among endometriosis subtypes and how their molecular signatures are related to phenotypic manifestations, we analyzed ovarian endometrial cyst (OEC), superficial peritoneal endometriosis (SPE), and deep infiltrating endometriosis (DIE) from 12 patients using single‐cell RNA‐sequencing (scRNA‐seq). We identified 11 cell clusters, including EEEC, EESC, fibroblasts, inflammatory/immune, endothelial, mesothelial, and Schwann cells. For hormonal signatures, EESCs, but not EEECs, showed high estrogen signatures (estrogen response scores and HOXA downregulation) and low progesterone signatures (DKK1 downregulation) compared to normal endometrium. In EEECs, we found MUC5B+ TFF3low cells enriched in endometriosis. In lymphoid cells, evidence for both immune activation (high cytotoxicity in NK) and exhaustion (high checkpoint genes in NKT and cytotoxic T) was identified in endometriosis. Signatures and subpopulations of macrophages were remarkably different among endometriosis subtypes with increased monocyte‐derived macrophages and IL1B expression in DIE. The scRNA‐seq predicted NRG1 (macrophage)‐ERBB3 (Schwann cell) interaction in endometriosis, expressions of which were validated by immunohistochemistry. Myofibroblast subpopulations differed according to the location (OECs from fibroblasts and SPE/DIEs from mesothelial cells and fibroblasts). Endometriosis endothelial cells displayed proinflammation, angiogenesis, and leaky permeability signatures that were enhanced in DIE. Collectively, our study revealed that (1) many cell types—endometrial, lymphoid, macrophage, fibroblast, and endothelial cells—are altered in endometriosis; (2) endometriosis cells show estrogen responsiveness, immunologic cytotoxicity and exhaustion, and proinflammation signatures that are different in endometriosis subtypes; and (3) novel endometriosis‐specific findings of MUC5B+ EEECs, mesothelial cell‐derived myofibroblasts, and NRG1‐ERBB3 interaction may underlie the pathogenesis of endometriosis. Our results may help extend pathologic insights, dissect aggressive diseases, and discover therapeutic targets in endometriosis. © 2023 The Pathological Society of Great Britain and Ireland.
A unique coupling agent for elastomer nanocomposites with better carbon black dispersion for higher abrasion resistance and lower rolling resistance
Authors: Gao Jiaming , Xing Yihao , An Lu , Ye Xin , Yao Hong , Wang Hong , Wu Xiaohui , Zhang Liqun 
Published: September 2023

AbstractCarbon black is a very important reinforcing agent for rubber, which can significantly improve rubber modulus, strength, and abrasion performance. However, there are defects such as large hysteresis loss, dynamic energy loss, and high heat build‐up by using carbon black to reinforce rubber. In this paper, a new silane coupling agent named M1 was prepared and introduced as the coupling agent of carbon black, and M1 modified carbon black was prepared. The Fourier transform infrared spectroscopy, thermogravimetric analysis, and X‐ray photoelectron spectrometer results demonstrated the successful modification and revealed the interaction mechanism between M1 and carbon black. The results showed that strong interfacial bonding can be generated between M1 and carbon black through physical and chemical interactions, thereby promoting the dispersion of carbon black in the rubber matrix. Then, carbon black/rubber nanocomposites were prepared with different amount of M1. Because M1 could improve the dispersion of carbon black in the rubber matrix, the carbon black/rubber nanocomposites with M1 have lower network and loss factor, lower rolling resistance, and higher abrasion resistance, which is ideal to manufacture green bus and truck tires for energy‐saving, environment‐friendly, and low‐carbon society.
Kalium 3.0 is a comprehensive depository of natural, artificial, and labeled polypeptides acting on potassium channels
Authors: Krylov Nikolay A. , Tabakmakher Valentin M. , Yureva Daria A. , Vassilevski Alexander A. , Kuzmenkov Alexey I. 
Published: September 2023

AbstractHere, we introduce the third release of Kalium database (http://kaliumdb.org/), a manually curated comprehensive depository that accumulates data on polypeptide ligands of potassium channels. The major goal of this amplitudinous update is to summarize findings for natural polypeptide ligands of K+ channels, as well as data for the artificial derivatives of these substances obtained over the decades of exploration. We manually analyzed more than 700 original manuscripts and systematized the information on mutagenesis, production of radio‐ and fluorescently labeled derivatives, and the molecular pharmacology of K+ channel ligands. As a result, data on more than 1200 substances were processed and added enriching the database content fivefold. We also included the electrophysiological data obtained on the understudied and neglected K+ channels including the heteromeric and concatenated channels. We associated target channels in Kalium with corresponding entries in the official database of the International Union of Basic and Clinical Pharmacology. Kalium was supplemented with an adaptive Statistics page, where users are able to obtain actual data output. Several other improvements were introduced, such as a color code to distinguish the range of ligand activity concentrations and advanced tools for filtration and sorting. Kalium is a fully open‐access database, crosslinked to other databases of interest. It can be utilized as a convenient resource containing ample up‐to‐date information about polypeptide ligands of K+ channels.
Use of plant viruses as bioherbicides: the first virus‐based bioherbicide and future opportunities
Authors: Charudattan Raghavan 
Published: September 2023

AbstractUntil recently, only a few plant viruses had been studied for use as biological control agents for weeds, but none had been developed into a registered bioherbicide. This position changed in 2014, when the US Environmental Protection Agency granted an unrestricted Section 3 registration for tobacco mild green mosaic virus (TMGMV) strain U2 as a herbicide active ingredient for a commercial bioherbicide (SolviNix LC). It is approved for the control of tropical soda apple (TSA, Solanum viarum), an invasive ‘noxious weed’ in the United States. TSA is a problematic weed in cattle pastures and natural areas in Florida. The TMGMV‐U2 product kills TSA consistently, completely, and within a few weeks after its application. It is part of the TSA integrated best management practice in Florida along with approved chemical herbicides and a classical biocontrol agent, Gratiana boliviana (Coleoptera: Chrysomelidae). TMGMV is nonpathogenic and nontoxic to humans, animals, and other fauna, environmentally safe, and as effective as chemical herbicides. Unlike the insect biocontrol agent, TMGMV kills and eliminates the weed from fields and helps recycle the dead biomass in the soil. Here the discovery, proof of concept, mode of action, risk analyses, application methods and tools, field testing, and development of the virus as the commercial product are reviewed. Also reviewed here are the data and scientific justifications advanced to answer the concerns raised about the use of the virus as a herbicide. The prospects for discovery and development of other plant‐virus‐based bioherbicides are discussed. © 2023 Society of Chemical Industry.
Wave propagation through a stationary field of clouds: A homogenisation approach
Authors: Goldsmith Edward J. , Esler James G. 
Published: September 2023

AbstractThe effect of a subgrid‐scale cloud field on the propagation of long atmospheric waves is investigated using a new scale‐consistent formulation based on the asymptotic theory of homogenisation. A key aim is to quantify potential model errors in wave propagation speeds, introduced by using averaged fields in place of the fully resolved circulation, in the setting of a simple stratified Boussinesq midlatitude ‐channel model. The effect of the cloud field, represented here by a random array of strongly nonlinear axisymmetric circulations, is found to appear in the large‐scale governing equations through new terms which redistribute the large‐scale buoyancy and horizontal momentum fields in the vertical. These new terms, which have the form of nonlocal integral operators, are linear in the cloud number density and are fully determined by the solution of a linear elliptic equation known as a cell problem. The cell problem in turn depends on the details of the nonlinear cloud circulations. The integral operators are calculated explicitly for example cloud fields and then dispersion relations are compared for different waves in the presence of clouds at realistic densities. The main finding is that baroclinic Rossby waves are significantly slowed and damped by the clouds, whilst inertia–gravity waves are affected almost exclusively by damping, most strongly at the lowest frequencies. In contrast, all waves with a barotropic structure are found to be almost unaffected by the presence of clouds, even at the highest realistic cloud densities. An important consequence of this study is a new approach to the closure of subgrid‐scale cloud fields in the parameterisation of convection in large‐scale atmospheric models.