bluuebunny/crossref_metadata_2025_split huggingface dataset:
A scalable hyperthermic intravesical chemotherapy (HIVEC) setup for rat models of bladder cancer
Authors: Van Hattum J. W. , Scutigliani E. M. , Helderman R. F. C. P. A. , Zweije R. , Rodermond H. M. , Oei A. L. , Crezee J. , Oddens J. R. , De Reijke T. M. , Krawczyk P. M. 
Published: April 2022

AbstractHyperthermic intravesical chemotherapy (HIVEC)—whereby the bladder is heated to ± 43 °C during a chemotherapy instillation—can improve outcomes of non-muscle invasive bladder cancer (NMIBC) treatments. Experiments in animal models are required to explore new hyperthermia based treatments. Existing HIVEC devices are not suitable for rodents or large-scale animal trials. We present a HIVEC setup compatible with orthotopic rat models. An externally heated chemotherapeutic solution is circulated in the bladder through a double-lumen catheter with flow rates controlled using a peristaltic pump. Temperature sensors in the inflow channel, bladder and outflow channel allow temperature monitoring and adjustments in real-time. At a constant flow rate of 2.5 mL/min the system rapidly reaches the desired bladder temperature of 42–43 °C with minimal variability throughout a one-hour treatment in a rat bladder phantom, as well as in euthanised and live rats. Mean intraluminal bladder temperatures were 42.92 °C (SD = 0.15 °C), 42.45 °C (SD = 0.37 °C) and 42.52 °C (SD = 0.09 °C) in the bladder phantom, euthanised, and live rats respectively. Thermal camera measurements showed homogenous heat distributions over the bladder wall. The setup provides well-controlled thermal dose and the upscaling needed for performing large scale HIVEC experiments in rats.
Rhegmatogenous retinal detachment induces more severe macular capillary changes than central serous chorioretinopathy
Authors: Lee Junyeop , Seo Eoi Jong , Yoon Young Hee 
Published: April 2022

AbstractTo investigate hemodynamic changes in macula-off rhegmatogenous retinal detachment (RRD) and its impact on visual prognosis by comparing with central serous chorioretinopathy (CSC). Using optical coherence tomography angiography (OCTA), vascular density in the superficial capillary plexus and deep capillary plexus (DCP) was retrospectively compared with that in contralateral unaffected eyes in macula-off RRD and CSC eyes. In RRD eyes, pre- and postoperative ultra-widefield (UWF) fluorescein angiography (FA) were obtained to analyze vascular changes. In OCTA, both macula-off RRD and CSC eyes showed less density in macular DCP, compared to the unaffected fellow eyes. Compared to CSC, eyes affected by macula-off RRD showed a reduction in DCP vascular density and an increase in foveal avascular zone area, although it had a much shorter macular detachment period. In macula-off RRD, less density of DCP was strongly correlated with longer duration of detachment, greater ellipsoid zone disruption, and poor visual recovery. In UWF-FA, detached retina showed capillary hypoperfusion, venous stasis and leakage, which were improved after reattachment. In conclusion, macular capillary loss of flow, which was associated with photoreceptor disruption, correlated with duration of detachment in RRD. Early reattachment and reperfusion are required for minimizing macular vasculature and photoreceptor damage in macula-off RRD.
Alternative polyadenylation associated with prognosis and therapy in colorectal cancer
Authors: Zhang Yi , Xu Yunfei , Wang Yuzhi 
Published: April 2022

AbstractColorectal cancer (CRC) is among the most widely spread cancers globally. Aberrant alternative polyadenylation (APA) plays a role in cancer onset and its progression. Consequently, this study focused on highlighting the role of APA events and signals in the prognosis of patients with CRC. The APA events, RNA sequencing (RNA-seq), somatic mutations, copy number variants (CNVs), and clinical information of the CRC cohort were obtained from The Cancer Genome Atlas (TCGA) database and UCSC (University of California-Santa Cruz) Xena database. The whole set was sorted into two sets: a training set and a test set in a ratio of 7:3. 197 prognosis-related APA events were collected by performing univariate Cox regression signature in patients with CRC. Subsequently, a signature for APA events was established by least absolute shrinkage and selection operator (LASSO) and multivariate Cox analysis. The risk scores were measured for individual patients on the basis of the signature and patients were sorted into two groups; the high-risk group and the low-risk group as per their median risk scores. Kaplan–Meier curves, principal component analysis (PCA), and time-dependent receiver operator characteristic (ROC) curves revealed that the signature was able to predict patient prognosis effectively and further validation was provided in the test set and the whole set. The high-risk and low-risk groups displayed various distributions of mutations and CNVs. Tumor mutation burden (TMB) alone and in combination with the signature predicted the prognosis of CRC patients, but the gene frequencies of TMBs and CNVs did not change in the low- and high-risk groups. Moreover, immunotherapy and chemotherapy treatments showed different responses to PD-1 inhibitors and multiple chemotherapeutic agents in the low and high-risk groups based on the tumor immune dysfunction and exclusion (TIDE) and genomics of drugs sensitivity in cancer (GDSC) databases. This study may help in understanding the potential roles of APA in CRC, and the signature for prognosis-related APA events can work as a potential predictor for survival and treatment in patients with CRC.
Topographical relocation of adolescent sleep spindles reveals a new maturational pattern in the human brain
Authors: Gombos Ferenc , Bódizs Róbert , Pótári Adrián , Bocskai Gábor , Berencsi Andrea , Szakács Hanna , Kovács Ilona 
Published: April 2022

AbstractCurrent theories of human neural development emphasize the posterior-to-anterior pattern of brain maturation. However, this scenario leaves out significant brain areas not directly involved with sensory input and behavioral control. Suggesting the relevance of cortical activity unrelated to sensory stimulation, such as sleep, we investigated adolescent transformations in the topography of sleep spindles. Sleep spindles are known to be involved in neural plasticity and in adults have a bimodal topography: slow spindles are frontally dominant, while fast spindles have a parietal/precuneal origin. The late functional segregation of the precuneus from the frontoparietal network during adolescence suggests that spindle topography might approach the adult state relatively late in development, and it may not be a result of the posterior-to-anterior maturational pattern. We analyzed the topographical distribution of spindle parameters in HD-EEG polysomnographic sleep recordings of adolescents and found that slow spindle duration maxima traveled from central to anterior brain regions, while fast spindle density, amplitude and frequency peaks traveled from central to more posterior brain regions. These results provide evidence for the gradual posteriorization of the anatomical localization of fast sleep spindles during adolescence and indicate the existence of an anterior-to-posterior pattern of human brain maturation.
Survival among subgroups of patients with stage II nasopharyngeal carcinoma
Authors: Huang Shi-Ting , Su Dan-Ke 
Published: April 2022

AbstractTo assess survival between subgroups (T1N1, T2N0, and T2N1) of patients with stage II nasopharyngeal carcinoma (NPC). This retrospective cohort study evaluated pathologically confirmed stage II NPC patients from The Surveillance, Epidemiology, and End Results (SEER) database from 2004 to 2016. The included patients were divided into three subgroups: T1N1, T2N0, and T2N1. Overall survival (OS) and cancer-specific survival (CSS) were assessed using the Kaplan–Meier method among the three subgroups. This study investigated 836 patients: 383 (45.8%) patients were in the T1N1 subgroup, 175 (20.9%) patients were in the T2N0 subgroup, and 278 (33.3%) patients were in the T2N1 subgroup. The 5-year OS (75.7%, 68.6%, and 75.7%) and CSS (85.3%, 83.4%, and 84.5%) were similar among the T1N1, T2N0, and T2N1 subgroups. Univariate and multivariate regression analyses revealed that the subgroup (T1N1, T2N0, and T2N1) of stage II NPC was not an independent prognostic factor for OS or CSS. Survival was comparable among subgroups (T1N1, T2N0, and T2N1) of stage II NPC patients. However, patients with T1N1, T2N0, and T2N1 stage disease who receive different treatments might have different prognoses.
Climate change will disproportionally affect the most genetically diverse lineages of a widespread African tree species
Authors: Lyam Paul T. , Duque-Lazo Joaquín , Hauenschild Frank , Schnitzler Jan , Muellner-Riehl Alexandra N. , Greve Michelle , Ndangalasi Henry , Myburgh Annerine , Durka Walter 
Published: April 2022

AbstractGlobal climate change is proceeding at an alarming rate with major ecological and genetic consequences for biodiversity, particularly in drylands. The response of species to climate change may differ between intraspecific genetic groups, with major implications for conservation. We used molecular data from 10 nuclear and two chloroplast genomes to identify phylogeographic groups within 746 individuals from 29 populations of Senegalia senegal, a savannah tree species in sub-Saharan Africa. Three phylogroups are identified corresponding to Sudano-Sahelian, Zambezian and Southern African biogeographic regions in West, East and Southern Africa. Genetic diversity was highest in Southern and Zambesian and lowest in the Sudano-Sahelian phylogroups. Using species distribution modeling, we infer highly divergent future distributions of the phylogroups under three climate change scenarios. Climate change will lead to severe reductions of distribution area of the genetically diverse Zambezian (− 41–− 54%) and Southern (− 63–− 82%) phylogroups, but to an increase for the genetically depauperate Sudano-Sahelian (+ 7– + 26%) phylogroups. This study improves our understanding of the impact of climate change on the future distribution of this species. This knowledge is particularly useful for biodiversity management as the conservation of genetic resources needs to be considered in complementary strategies of in-situ conservation and assisted migration.
Changes in ventilation distribution in children with neuromuscular disease using the insufflator/exsufflator technique: an observational study
Authors: Casaulta Carmen , Messerli Florence , Rodriguez Romy , Klein Andrea , Riedel Thomas 
Published: April 2022

AbstractPatients with neuromuscular disease often suffer from weak and ineffective cough resulting in mucus retention and increased risk for chest infections. Different airway clearance techniques have been proposed, one of them being the insufflator/exsufflator technique. So far, the immediate physiological effects of the insufflator/exsufflator technique on ventilation distribution and lung volumes are not known. We aimed to describe the immediate effects of the insufflator/exsufflator technique on different lung volumes, forced flows and ventilation distribution. Eight subjects (age 5.8–15.2 years) performed lung function tests including spirometry, multiple breath washout and electrical impedance tomography before and after a regular a chest physiotherapy session with an insufflator/exsufflator device. Forced lung volumes and flows as well as parameters of ventilation distribution derived from multiple breath washout and electrical impedance tomography were compared to assess the short-term effect of the therapy. In this small group of stable paediatric subjects with neuromuscular disease we could not demonstrate any short-term effects of insufflation/exsufflation manoeuvres on lung volumes, expiratory flows and ventilation distribution. With the currently used protocol of the insufflation/exsufflation manoeuvre, we cannot demonstrate any immediate changes in lung function.
Computational profiling of hiPSC-derived heart organoids reveals chamber defects associated with NKX2-5 deficiency
Authors: Feng Wei , Schriever Hannah , Jiang Shan , Bais Abha , Wu Haodi , Kostka Dennis , Li Guang 
Published: April 2022

AbstractHeart organoids have the potential to generate primary heart-like anatomical structures and hold great promise as in vitro models for cardiac disease. However, their properties have not yet been fully studied, which hinders their wide spread application. Here we report the development of differentiation systems for ventricular and atrial heart organoids, enabling the study of heart diseases with chamber defects. We show that our systems generate chamber-specific organoids comprising of the major cardiac cell types, and we use single cell RNA sequencing together with sample multiplexing to characterize the cells we generate. To that end, we developed a machine learning label transfer approach leveraging cell type, chamber, and laterality annotations available for primary human fetal heart cells. We then used this model to analyze organoid cells from an isogeneic line carrying an Ebstein’s anomaly associated genetic variant in NKX2-5, and we successfully recapitulated the disease’s atrialized ventricular defects. In summary, we have established a workflow integrating heart organoids and computational analysis to model heart development in normal and disease states.
Turbulence-induced bubble nucleation in hydrothermal fluids beneath Yellowstone Lake
Authors: Caudron Corentin , Vandemeulebrouck Jean , Sohn Robert A. 
Published: April 2022

AbstractVolcanic systems generate large amounts of gas, and understanding gas fluxes is a fundamental aspect of volcanology and hazard mitigation. Volcanic gases can be challenging to measure, but acoustic methods hold promise in underwater environments because gas bubbles are powerful sound sources. We deployed an acoustic system to study the nature of gas discharge at a large (~30 MW) thermal field on the floor of Yellowstone Lake, which has experienced numerous hydrothermal explosions since the last glaciation (~13.4 ka). We find that small (<10 Pa) turbulent flow instabilities trigger the nucleation of CO2 bubbles in the saturated fluids. The observation of CO2 bubbles nucleating in hydrothermal fluids due to small pressure perturbations informs our understanding of hydrothermal explosions in Yellowstone Lake, and demonstrates that acoustic data in underwater environments can provide insight into the stability of gas-rich systems, as well as gas fluxes.
Substructure in the stellar halo near the Sun
Authors: Ruiz-Lara T. , Matsuno T. , Lövdal S. S. , Helmi A. , Dodd E. , Koppelman H. H. 
Published: April 2022

Context. In an accompanying paper, we present a data-driven method for clustering in ‘integrals of motion’ space and apply it to a large sample of nearby halo stars with 6D phase-space information. The algorithm identified a large number of clusters, many of which could tentatively be merged into larger groups.
Aims. The goal here is to establish the reality of the clusters and groups through a combined study of their stellar populations (average age, metallicity, and chemical and dynamical properties) to gain more insights into the accretion history of the Milky Way.
Methods. To this end, we developed a procedure that quantifies the similarity of clusters based on the Kolmogorov–Smirnov test using their metallicity distribution functions, and an isochrone fitting method to determine their average age, which is also used to compare the distribution of stars in the colour–absolute magnitude diagram. Also taking into consideration how the clusters are distributed in integrals of motion space allows us to group clusters into substructures and to compare substructures with one another.
Results. We find that the 67 clusters identified by our algorithm can be merged into 12 extended substructures and 8 small clusters that remain as such. The large substructures include the previously known Gaia-Enceladus, Helmi streams, Sequoia, and Thamnos 1 and 2. We identify a few over-densities that can be associated with the hot thick disc and host a small metal-poor population. Especially notable is the largest (by number of member stars) substructure in our sample which, although peaking at the metallicity characteristic of the thick disc, has a very well populated metal-poor component, and dynamics intermediate between the hot thick disc and the halo. We also identify additional debris in the region occupied by Sequoia with clearly distinct kinematics, likely remnants of three different accretion events with progenitors of similar masses. Although only a small subset of the stars in our sample have chemical abundance information, we are able to identify different trends of [Mg/Fe] versus [Fe/H] for the various substructures, confirming our dissection of the nearby halo.
Conclusions. We find that at least 20% of the halo near the Sun is associated to substructures. When comparing their global properties, we note that those substructures on retrograde orbits are not only more metal-poor on average but are also older. We provide a table summarising the properties of the substructures, as well as a membership list that can be used for follow-up chemical abundance studies for example.
Viscous inertial modes on a differentially rotating sphere: Comparison with solar observations
Authors: Fournier Damien , Gizon Laurent , Hyest Laura 
Published: April 2022

Context. In a previous paper, we studied the effect of latitudinal rotation on solar equatorial Rossby modes in the β-plane approximation. Since then, a rich spectrum of inertial modes has been observed on the Sun, which is not limited to the equatorial Rossby modes and includes high-latitude modes.
Aims. Here we extend the computation of toroidal modes in 2D to spherical geometry using realistic solar differential rotation and including viscous damping. The aim is to compare the computed mode spectra with the observations and to study mode stability.
Methods. At a fixed radius, we solved the eigenvalue problem numerically using a spherical harmonics decomposition of the velocity stream function.
Results. Due to the presence of viscous critical layers, the spectrum consists of four different families: Rossby modes, high-latitude modes, critical-latitude modes, and strongly damped modes. For each longitudinal wavenumber m ≤ 3, up to three Rossby-like modes are present on the sphere, in contrast to the equatorial β plane where only the equatorial Rossby mode is present. The least damped modes in the model have eigenfrequencies and eigenfunctions that resemble the observed modes; the comparison improves when the radius is taken in the lower half of the convection zone. For radii above 0.75 R⊙ and Ekman numbers E < 10−4, at least one mode is unstable. For either m = 1 or m = 2, up to two Rossby modes (one symmetric and one antisymmetric) are unstable when the radial dependence of the Ekman number follows a quenched diffusivity model (E ≈ 2 × 10−5 at the base of the convection zone). For m = 3, up to two Rossby modes can be unstable, including the equatorial Rossby mode.
Conclusions. Although the 2D model discussed here is highly simplified, the spectrum of toroidal modes appears to include many of the observed solar inertial modes. The self-excited modes in the model have frequencies close to those of the observed modes with the largest amplitudes.
Complications in Endoscopic Endonasal Pituitary Adenoma Surgery: An Institution Experience in 310 Patients
Authors: Namvar Mohamad , Iranmehr Arad , Fathi Mohamad Reza , Sadrhosseini Seyed Mousa , Tabari Azin , Shirzad Noushin , Zeinalizadeh Mehdi 
Published: April 2022

Abstract
Objective Endoscopic endonasal approaches (EEAs) have shown excellent results for majority of hypophyseal tumors. The aim of this study was to evaluate and report the complications of EEA in patients with pituitary adenoma (PA) who underwent surgery between 2013 and 2018.
Methods We performed a retrospective review of 310 consecutive patients/325 procedures with PA treated with an EEA from May 2013 to January 2018. Minor complications including transient diabetes insipidus (DI) or new anterior pituitary hormone insufficiency in one axis and major complications including CSF leakage, hematoma needing reoperation, vascular damage, brain infection, new pan-hypopituitarism permanent DI, new visual impairment, neurological deficits, and mortality were recorded.
Results We encountered 58 complications in 310 patients (18.7%) and 325 procedures (17.7%). Minor complications were 43 (13.9 and 13.2%) in 310 patients and in 325 procedures, respectively; whereas, major complications were 28 (9 and 8.6%, respectively). Total complications were associated with diameter group 2 (>30 mm), diaphragm sella violation, suprasellar extension, parasellar involvement, nonfunctional secretory type, and intraoperative arachnoid tearing.
Conclusion EEA can be considered as a safe surgical treatment which has acceptable complications in the management of PAs.
Perioperative Coagulation Profile in Major Liver Resection for Cancer: A Prospective Observational Study
Authors: Tzimas Petros , Lefkou Eleftheria , Karakosta Agathi , Argyrou Stellios , Papapetrou Evangelia , Pantazi Despoina , Tselepis Alexandros , Dreden Patrick Van , Stratigopoulou Panagiota , Gerotziafas Grigoris , Glantzounis Georgios 
Published: April 2022

AbstractHepatectomy-induced coagulation disturbances have been well studied over the past decade. Cumulative evidence supports the superiority of global coagulation analysis compared with conventional coagulation tests (i.e., prothrombin time or activated partial thromboplastin time) for clinical decision making. Cancer, however, represents an acquired prothrombotic state and liver resection for cancer deserves a more thorough investigation. This prospective observational study was conducted to assess the perioperative coagulation status of patients undergoing major hepatectomies for primary or metastatic hepatic malignancy. Patients were followed up to the 10th post-operative day by serial measurements of conventional coagulation tests, plasma levels of coagulation factors, and thrombin generation assay parameters. An abnormal coagulation profile was detected at presentation and included elevated FVIII levels, decreased levels of antithrombin, and lag time prolongation in thrombin generation. Serial hematological data demonstrated increased Von Willebrand factor, FVIII, D-dimer, fibrinogen and decreased levels of natural anticoagulant proteins in the early post-operative period predisposing to a hyper-coagulable state. The ratio of the anticoagulant protein C to the procoagulant FVIII was low at baseline and further declined post-operatively, indicating a prothrombotic state. Though no bleeding complications were reported, one patient experienced pulmonary embolism while under thromboprophylaxis. Overall, patients with hepatic carcinoma presenting for elective major hepatectomy may have baseline malignancy-associated coagulation disturbances, aggravating the hyper-coagulable state documented in the early post-operative period.