bluuebunny/crossref_metadata_2025 huggingface dataset:
Short- and long-term stability of synthetic cathinones and dihydro-metabolites in human urine samples
Authors: Aldubayyan Abdulaziz A. , Castrignanò Erika , Elliott Simon , Abbate Vincenzo
Published: March 2024

Purpose

Synthetic cathinones constitute the second largest group of new psychoactive substances, which are often used for recreational purposes and reported in toxicological analysis. Various factors may influence the stability of synthetic cathinones between sampling and analysis, and therefore, stability studies are required to determine the best storage conditions as well as extend the period of detection.

Methods

This study involved sixteen synthetic cathinones and ten dihydro-metabolites spiked in human urine to evaluate the stability under common storage conditions to imitate real forensic toxicology samples. The samples were stored at either room temperature (22–23 °C) for up to 3 days, refrigerated (4 °C) for up to 14 days or frozen (–40 °C) for up to 12 months, and analyzed in triplicate using a validated liquid chromatography–tandem mass spectrometry method.

Results

Analytes’ concentrations decreased over time, although slower when stored frozen. All analytes remained stable (> 80%) for 1 month when stored frozen before losses in content were more apparent for some compounds, depending on their chemical structure. Under all storage conditions, the highest instability was observed for analytes containing halogens (i.e., chlorine or fluorine). Thus, halogenated analytes were further investigated by using liquid chromatography coupled to quadruple time-of-flight mass spectrometry to attempt identifying degradation products.

Conclusions

Irrespective of parent analytes, dihydro-metabolites had improved stability at each tested temperature, which highlights their importance as appropriate urine biomarkers when retesting is required after a long period of storage.
Analysis of guide wire displacement in robot-assisted spinal pedicle screw implantation
Authors: Liu Qing , Wang RuiYang , Ru Neng , Wu Yu , Guo ChangJin , Chen LeYuan , Liang Jie , Zhang Fan
Published: March 2024

Robot-assisted pedicle screw placement is prone to guide wire migration, and the related influencing factors have not yet been discussed. Therefore, this study aimed to investigate and analyze the causes of robot-assisted spinal pedicle guide wire displacement and summarize the relevant treatment strategies. The surgical outcomes of 82 patients who underwent robotic-assisted pedicle screw spinal placement at our hospital between July 2022 and June 2023 were retrospectively analyzed. A total of 342 screws were placed in 82 patients; 47 guide wires were offset, 47 guide wires were replaced, and 295 guide wires were not significantly offset, with a first guide wire offset rate of 13.7% and a total guide wire offset rate of 12.1%. Univariate analysis showed that Screw placement level, whether respiration was controlled during guide wire placement, Hu value of CT, the position of needle insertion point, and operation time had a significant effect on guide wire deviation (P < 0.05). Multivariate logistic regression analysis showed that the inclusion of screw placement segments, whether breathing was controlled during guide wire placement, and Hu value of CT had a significant effect on guide wire offset (P < 0.05). Whether the guide wire was offset had no significant effect on the accuracy of subsequent pedicle screw implantation (P > 0.05). The level of screw placement, whether breathing was controlled during guide wire placement, and Hu value of CT were independent risk factors for guide wire deviation. When causing an excursion, screw orientation can be adjusted during intraoperative screw placement, and guide wire excursion has no significant impact on the accuracy of subsequent pedicle screw placement.
Emerging multi-port soft tissue robotic systems: a systematic review of clinical outcomes
Authors: Leang Yit J. , Kong Joseph C. H. , Mosharaf Zahin , Hensman Chrys S. , Burton Paul R. , Brown Wendy A.
Published: March 2024

Multiple novel multi-port robotic surgical systems have been introduced into clinical practice. This systematic review aims to evaluate the clinical outcomes of these novel robotic systems to conventional laparoscopic technique and established da Vinci robotic surgical platforms. A literature search of Embase, Medline, Pubmed, Cochrane library, and Google Scholar was performed according to the PRISMA guidelines from 2012 to May 2023. Studies comparing clinical outcomes of novel multi-port robotic surgical systems with laparoscopic or the da Vinci platforms were included. Case series with no comparison groups were excluded. Descriptive statistics were used to report patient and outcome data. A systematic narrative review was provided for each outcome. Twelve studies comprised of 1142 patients were included. A total of 6 novel multi-port robotic systems: Micro Hand S, Senhance, Revo-i MSR-5000, KangDuo, Versius, and Hugo™ RAS were compared against the laparoscopic or the da Vinci robotic platforms. Clinical outcomes of these novel robotic platforms were comparable to the established da Vinci platforms. When compared against conventional laparoscopic approaches, the robotic platforms demonstrated lower volume of blood loss, shorter length of stay but longer operative time. This systematic review highlighted the safe implementation and efficacy of 6 new robotic systems. The clinical outcomes achieved by these new robotic systems are comparable to the established da Vinci robotic system in simple to moderate case complexities. There is emerging evidence that these new robotic systems provide a viable alternative to currently available robotic platforms.
The deconstructed procedural description in robotic colorectal surgery
Authors: Larkins Kirsten , Quirke Ned , Ong Hwa Ian , Mohamed Jade El , Heriot Alexander , Warrier Satish , Mohan Helen
Published: March 2024

Increasing robotic surgical utilisation in colorectal surgery internationally has strengthened the need for standardised training. Deconstructed procedural descriptions identify components of an operation that can be integrated into proficiency-based progression training. This approach allows both access to skill level appropriate training opportunities and objective and comparable assessment. Robotic colorectal surgery has graded difficulty of operative procedures lending itself ideally to component training. Developing deconstructed procedural descriptions may assist in the structure and progression components in robotic colorectal surgical training. There is no currently published guide to procedural descriptions in robotic colorectal surgical or assessment of their training utility. This scoping review was conducted in June 2022 following the PRISMA-ScR guidelines to identify which robotic colorectal surgical procedures have available component-based procedural descriptions. Secondary aims were identifying the method of development of these descriptions and how they have been adapted in a training context. 20 published procedural descriptions were identified covering 8 robotic colorectal surgical procedures with anterior resection the most frequently described procedure. Five publications included descriptions of how the procedural description has been utilised for education and training. From these publications terminology relating to using deconstructed procedural descriptions in robotic colorectal surgical training is proposed. Development of deconstructed robotic colorectal procedural descriptions (DPDs) in an international context may assist in the development of a global curriculum of component operating competencies supported by objective metrics. This will allow for standardisation of robotic colorectal surgical training and supports a proficiency-based training approach.
The effect of metabolic syndrome on prognosis of diffuse large B-cell lymphoma
Authors: Xiong Wenjing , Li Liru , Hui Xue , Liu Yue , Li Hongbin , Zhang Yue , Zhao Shu
Published: March 2024

Purpose

Metabolic syndrome (MetS), characterized by insulin resistance, is closely associated with the prognosis of various cancer types, but has not been reported in diffuse large B-cell lymphoma (DLBCL). The aim of this study is to examine how other clinicopathological variables and the MetS influence the prognosis of DLBCL.

Methods

Clinical and pathological data were collected from 319 patients with DLBCL who were admitted to our hospital between January 2012 and December 2020. The data accessible with SPSS 27.0 enables the utilization of various statistical methods for clinical data analysis, including independent sample t test and univariate and multivariate COX regression.

Results

The presence of MetS was linked to both overall survival (OS) and progression-free survival (PFS), in addition to other clinicopathological characteristics as age, IPI score, rituximab usage, and Ki-67 expression level. This link with OS and PFS indicated a poor prognosis, as shown by survival analysis. Subsequent univariate analysis identified IPI score, Ki-67 expression level, tumor staging, rituximab usage, lactate dehydrogenase expression level, and the presence or absence of MetS as factors linked with OS and PFS. Furthermore, multivariate Cox regression analysis confirmed the independent risk factor status of IPI score, Ki-67 expression level, rituximab usage, and the presence of MetS in evaluating the prognosis of patients with DLBCL.

Conclusion

This study’s findings indicate that patients with pre-treatment MetS had a poor prognosis, with relatively shorter OS and PFS compared to those without pre-treatment MetS. Furthermore, the presence of MetS, IPI score, Ki-67 expression level, and rituximab usage were identified as independent risk factors significantly affecting the prognosis of DLBCL.
Production of Aroma-Rich Extracts from Sardine Cooking Wastewaters: Exploring Their Potential for Modulating Feed Intake in European Seabass
Authors: Resende Daniela , Pereira Maria J. , Sá Tiago , Brazinha Carla , Pintado Manuela , Valente Luisa M. P. , Velasco Cristina
Published: March 2024

Managing the canning industry’s nutrient-rich and odorous liquid waste is a hurdle. Concurrently, the growing use of vegetable ingredients in aquafeeds diminishes palatability and feed consumption in carnivorous fish. Thus, we hypothesized that aromas could be extracted from cooking wastewaters at canning factories and added to plant-based diets to stimulate intake in European seabass. Sardine cooking wastewaters were collected and tested directly (CW-A) or after vacuum distillation (VD-A) or liquid/liquid extraction with soybean oil (LLE-A). Despite losses in aldehydes and short-chain alcohols, both processes were effective in removing off-flavours. VD-A displayed a higher concentration of most aromas compared to LLE-A. Extracts were included at 2 μg g−1 of 1-penten-3-ol, the most abundant compound in all extracts, in diets (CW, VD, LLE). A non-supplemented diet was used as control. Each diet was assigned to six groups of juvenile fish, fed a single meal until apparent satiation. Our emphasis was on this initial feeding to comprehend the hedonic control of feed intake, minimizing habituation effects and the impact of the long-term metabolic requirements. Feed intake was highest for the control group. No differences on plasma metabolites were observed, suggesting feed intake was primarily regulated by hedonic rather than homeostatic mechanisms. Moreover, the lower intake in the supplemented diets was partially associated with a lower expression of orexigenic (intake-promoting) neuropeptides and higher expression of anorexigenic (intake-reducing) neuropeptides in the brain, despite the lack of significant diet-related differences. Overall, this study presents a novel approach to valorise cooking wastewater from the canning industry, since cooking wastewaters extracts rich in aromas were successfully produced, however, in the tested concentration, had no positive impact on the short-term feed intake response of European seabass.

Graphical Abstract
Post-cellular biotic evolution in a nutshell
Authors: Schubert Ingo
Published: March 2024

The minimum requirements for post-cellular evolution from prokaryotes towards multicellular eukaryotes are outlined. The main steps are: formation of a true nucleus harboring linear chromosomes with centromeres and telomeres, establishing of mitosis and of sex via meiosis and fertilization, endosymbiotic gain of mitochondria and plastids, and epigenetic differentiation of non-separated cells into tissues of multicellular organisms. Erroneous DNA double-strand break repair and cell fusion are postulated as main drivers of eukaryotic evolution. Advantages versus disadvantages of eukaryotes compared to prokaryotes are discussed.
Thymic hyperplasia is accurate to detect new-onset Graves’ hyperthyroidism and resolves after restoring euthyroidism
Authors: Scappaticcio L. , Caruso P. , Di Martino N. , Ferrazzano P. , Clemente A. , Maiorino M. I. , Regginelli A. , Docimo G. , Rambaldi P. F. , Bellastella G. , Trimboli P. , Cappabianca S. , Esposito K.
Published: March 2024

Purpose

Abnormal liver blood tests (ALBTs), neutropenia (NEU) and thymic hyperplasia (TH) are new features of Graves' disease (GD). Our objectives were: (a) to calculate the accuracy of TH in discriminating between Graves’ and non-Graves’ thyrotoxicosis, compared to ALBTs, NEU and Graves’ orbitopathy (GO); (b) to explore the outcome of GD-associated TH and non-GD-associated TH.

Methods

We prospectively analyzed consecutive adult patients with newly diagnosed thyrotoxicosis from January 2018 to June 2023. TH was detected via neck ultrasound (nUS) then confirmed and followed by magnetic resonance imaging (MRI). For GD vs non-GD clinical sensitivity (SE) and specificity (SPEC), accuracy, positive predictive value (PPV) and negative predictive value (NPV) of GO, TH, ALBTs and NEU were calculated.

Results

264 thyrotoxic patients were included. TH was found in 16.4% (20/122) of GD vs 1.4% (2/142) in non-GD (p < 0.001). SE, SPEC, accuracy, PPV and NPV of the four extrathyroidal manifestations of GD were as follows, respectively: GO 26%, 100%, 66%, 100%, 61%; ALBTs 41%, 89%, 69%, 76%, 66%; NEU 5%, 100%, 56%, 100%, 55%; TH 16%, 98%, 61%, 91%, 98%. In 18 of them, TH regressed within 12 months after achieving euthyroidism under anti-thyroid drug therapy, while in the remaining 2, TH regressed 6 months after thyroid surgery. In the two non-GD patients with TH, thymus disappeared along with euthyroidism.

Conclusions

TH in the hyperthyroidism scenario provides a high PPV for GD. A conservative approach for the diagnostic work‐up and initial management of thyrotoxicosis-associated TH should be adopted.
A novel tri-stage with reward-switching mechanism for constrained multiobjective optimization problems
Authors: Qu Jiqing , Li Xuefeng , Xiao Hui
Published: March 2024

The effective exploitation of infeasible solutions plays a crucial role in addressing constrained multiobjective optimization problems (CMOPs). However, existing constrained multiobjective optimization evolutionary algorithms (CMOEAs) encounter challenges in effectively balancing objective optimization and constraint satisfaction, particularly when tackling problems with complex infeasible regions. Subsequent to the prior exploration, this paper proposes a novel tri-stage with reward-switching mechanism framework (TSRSM), including the push, pull, and repush stages. Each stage consists of two coevolutionary populations, namely $${\text {Pop}}_1$$

Pop
1

and $${\text {Pop}}_2$$

Pop
2

. Throughout the three stages, $${\text {Pop}}_1$$

Pop
1

is tasked with converging to the constrained Pareto front (CPF). However, $${\text {Pop}}_2$$

Pop
2

is assigned with distinct tasks: (i) converging to the unconstrained Pareto front (UPF) in the push stage; (ii) utilizing constraint relaxation technique to discover the CPF in the pull stage; and (iii) revisiting the search for the UPF through knowledge transfer in the repush stage. Additionally, a novel reward-switching mechanism (RSM) is employed to transition between different stages, considering the extent of changes in the convergence and diversity of populations. Finally, the experimental results on three benchmark test sets and 30 real-world CMOPs demonstrate that TSRSM achieves competitive performance when compared with nine state-of-the-art CMOEAs. The source code is available at https://github.com/Qu-jq/TSRSM.
An algebraic characterization of entire polynomial diffeomorphisms
Authors: Xavier Frederico
Published: March 2024

It is shown that a polynomial map $$F: {\mathbb {R}}^n \rightarrow {\mathbb {R}}^n$$

F
:

R

n

→

R

n

with nowhere zero Jacobian determinant is invertible if and only if an explicit auxiliary polynomial system admits only the trivial solution. The main corollary is a concrete invertibility criterion in the Jacobian conjecture. The proof, conceptually related to differential geometry, represents a simple but infrequent application of differential equations to algebra.
The impact of contract farming on income of smallholder vegetables farmers in the central rift valley of Ethiopia
Authors: Neme Abdisa Abe , Tefera Tesfaye Lemma , Abdi Bedru Beshir , Aweke Chanyalew Seyoum
Published: March 2024

Recently, due attention was given to the commercialization of smallholder agriculture through contact farming, hoping that it would bring the positive impact on the income of smallholder producer in Ethiopia. This article presents the results of data analysis conducted to generate empirical data required to inform the smallholder agricultural commercialization policy using data collected from 424 (194 participants and 230 non-participants) randomly selected vegetables producer farmers from the 2 districts of the East shewa zone of the Oromia Regional State, Ethiopia. The propensity score matching was used to assess the impact of contract farming (CF) on smallholder farmers’ income in the study area. The probit model result shows that, the proportion of total crop area allocated to vegetables, access to credit, frequency of extension contacts, market information, and distance of the market center havepositive and significance effects on decision of vegetable producers to participate on the CF. The impact assessment result using PSM reveals that, gross annual income of the contract participants were lower by the 3.8% (Birr 2942) as compared to the non- participants. This implies that, local context matters for the success of CF and improves their livelihood. However, some of the CF participants would like to continue for access of production inputs, access to credit, technical advice and to reduce marketing risks and uncertainty. In conclusion, CF is a useful institutional arrangement which increases smallholders’ income and benefit from remunerative value chains agriculture, but it is not a panacea that works in different contexts. Hence, policy makers should base their choices on empirical evidence and local context to consider alternative and complementary intervention options to enhance smallholder commercialization and ensure sustainable livelihood in the research area.
Role of Ice Mechanics on Snow Viscoplasticity
Authors: Védrine Louis , Hagenmuller Pascal , Gélébart Lionel , Montagnat Maurine , Bernard Antoine
Published: March 2024

The porous structure of snow becomes denser with time under gravity, primarily due to the creep of its ice matrix with viscoplasticity. Despite investigation of this behavior at the macroscopic scale, the driving microscopic mechanisms are still not well understood. Thanks to high‐performance computing and dedicated solvers, we modeled snow elasto‐viscoplasticity with 3D images of its microstructure and different mechanical models of ice. The comparison of our numerical experiments to oedometric compression tests measured by tomography showed that ice in snow rather behaves as a heterogeneous set of ice crystals than as homogeneous polycrystalline ice. Similarly to dense ice, the basal slip system contributed at most, in the simulations, to the total snow deformation. However, in the model, the deformation accommodation between crystals was permitted by the pore space and did not require any prismatic and pyramidal slips, whereas the latter are pre‐requisite for the simulation of dense ice.
Electron Resonant Interaction With Coherent ULF Waves: Hamiltonian Approach
Authors: Artemyev Anton , An Xin , Vainchtein Dmitri , Rankin Robert , Zhou Xuzhi , Li Li , Zhang Xiao‐Jia
Published: March 2024

Electron resonant interaction with ultra‐low‐frequency (ULF) waves is considered to be a driver of electron radial transport in Earth’s inner magnetosphere. Traditional concept of such interaction assumes the electron slow diffusive scattering by a broad‐band ULF spectrum, but recent spacecraft observations reported a possibility for electrons to resonate nonlinearly with intense coherent ULF waves. This study proposes a theoretical model describing the main elements of such nonlinear resonant interactions. We implement a Hamiltonian approach to describe equatorial electron motion in a dipole magnetic field and electric ULF wavefield and demonstrate the ULF‐electron interactions has two basic nonlinear resonant regimes: phase bunching and phase trapping. Finally, we discuss possible applications of the proposed theoretical approach and the importance of ULF‐electron nonlinear resonances.
Ion Dynamics Across a Low Mach Number Bow Shock
Authors: Graham D. B. , Khotyaintsev Yu. V. , Dimmock A. P. , Lalti A. , Boldú J. J. , Tigik S. F. , Fuselier S. A.
Published: March 2024

A thorough understanding of collisionless shocks requires knowledge of how different ion species are accelerated across the shock. We investigate a bow shock crossing using the Magnetospheric Multiscale spacecraft after a coronal mass ejection crossed Earth, which led to solar wind consisting of protons, alpha particles, and singly charged helium ions. The three species are resolved upstream of the shock. The low Mach number of the bow shock enabled the ions to be partly distinguished downstream of the shock due to the relatively low ion heating. Some of the protons are specularly reflected and produce quasi‐periodic fine structures in the velocity distribution functions downstream of the shock. Heavier ions are shown to transit the shock without reflection. However, the gyromotion of the heavier ions partially obscures the fine structure of proton distributions. Additionally, the calculated proton moments are unreliable when the different ion species are not distinguished by the particle detector. The need for high time‐resolution mass‐resolving ion detectors when investigating collisionless shocks is discussed.
Recent Challenges in the APCC Multi‐Model Ensemble Seasonal Prediction: Hindcast Period Issue
Authors: Min Young‐Mi , Im Chang‐Mook , Kryjov Vladimir N. , Jeong Daeun
Published: March 2024

Seasonal forecasts are commonly issued in the form of anomalies, which are departures from the average over a specified multiyear reference period (climatology). The model climatology is estimated as the average of the retrospective forecasts over the hindcast period. However, different operational centers that provide seasonal ensemble predictions use different hindcast periods based on their model climatology. Additionally, the hindcast periods of recently developed and upgraded newer models have shifted in the recent years. In this paper, we discuss the recent challenges faced by APCC multi‐model ensemble (MME) operations, especially changes in the hindcast period for individual models. Based on the results of various experiments for MME prediction, we propose changing the hindcast period, which is the most appropriate solution for APCC operation. This makes the newly developed models join the MME and increases the total number of participating models, which facilitates the skill improvement of the MME prediction.
Electrical Alignment Signatures of Ice Particles Before Intracloud Lightning Activity Detected by Dual‐Polarized Phased Array Weather Radar
Authors: Wang Shuo , Wada Yuuki , Hayashi Syugo , Ushio Tomoo , Chandrasekar V.
Published: March 2024

The cloud electrification process has great significance in understanding the microphysical properties, electrical characteristics, and evolution of thunderstorms. This study employs an X‐band dual‐polarized multiparameter phased array weather radar (MP‐PAWR) to observe the electrical alignment signatures of ice particles before the first intracloud (IC) lightning flash, and to explore the evolution of the upper charge region in the early electrification stage of an isolated thunderstorm. Negative KDP signatures associated with vertically oriented ice particles by strong electric fields in the upper parts of the thunderstorm are analyzed by introducing composite KDP, which is defined as a minimum KDP value observed in a vertical column across all elevation scans at each specific horizontal grid point at and above a designated layer. About 7 min before the first IC lightning flash, the mean canting angle of ice particles in the upper parts of the cloud changed from horizontal to vertical by strong electric fields, and the concentration of vertically aligned ice particles on the top of the cloud reached the maximum 30 s before the first IC lightning flash. These signatures exhibit an early electrification process in the upper parts of the thunderstorm. These results indicate that with the high spatial and temporal resolution, MP‐PAWRs have the ability not only to detect the rapid evolution of microphysical structures but also to observe the early electrification of thunderstorms, which will facilitate forecasting IC lightning flash initiation combined with graupel presence signatures in the mixed‐phase region in normal operation.
The Remote Response in the Northern Pacific Climate During Winter to Deforestation in the Maritime Continent
Authors: Xiao He‐Ming , Hsu Huang‐Hsiung , Lee Ting‐Hui , Jong Bor‐Ting , Yu Jin‐Yi , Liang Yu‐Chiao , Lo Min‐Hui
Published: March 2024

The Maritime Continent (MC) has experienced significant anthropogenic land use changes, mainly deforestation, which has led to local surface warming and marked convergence in the lower troposphere and divergence in the upper. The remote consequences of this deforestation remain unclear and present considerable uncertainties. In this study, we employ a fully coupled climate model and a linear baroclinic model to explore the effects of altered land‐atmosphere interactions due to MC deforestation on high‐latitude climates. Our series of idealized experiments demonstrates that MC deforestation can induce upper‐level diabatic heating. This generates a barotropic Rossby wave that moves poleward, drawing energy from the subtropical jet across the Central to Eastern Pacific regions via eddy‐mean flow interactions. Such interactions amplify the Aleutian Low, promoting the northward transport of warm air, leading to notable warming anomalies. This influx of warmth contributes to sea ice melt, initiating a positive ice‐albedo feedback. A lapse‐rate feedback is also observed in adjacent high‐latitude land areas, amplifying terrestrial warming. These reinforcing feedbacks, combined with the direct temperature transport enabled by the strengthened Aleutian Low, cumulatively result in pronounced high‐latitude warming originally due to the tropical land use changes.
Physical and Biogeochemical Phenology of Coastal Upwelling in the California Current System
Authors: Jorgensen Ellen M. , Hazen Elliott L. , Jacox Michael G. , Pozo Buil Mercedes , Schroeder Isaac , Bograd Steven J.
Published: March 2024

In the California Current System (CCS), changes in the phenology (i.e., seasonal timing) of coastal upwelling alter the functioning of this productive marine ecosystem. Recently developed coastal upwelling indices that account for upwelling strength and nutrient flux to the surface provide a more complete understanding of bottom‐up forcing in the region. Using these indices, we describe CCS upwelling phenological variability in vertical transport and nutrient flux. Physical and biogeochemical spring transitions generally co‐occur in winter or spring, followed by increased upwelling and nutrient flux. In the latter half of the year, upwelling continues but nutrient flux wanes as declining source nutrient concentrations limit the biological efficacy of coastal upwelling. Earlier spring transitions and higher season‐integrated upwelling intensity occur during strong La Niña events at all latitudes, driven largely by stronger alongshore wind stress. Understanding phenological changes in coastal upwelling is critical, as they could have significant ecosystem consequences.
Citrate anticoagulation and systemic heparin anticoagulation during continuous renal replacement therapy among critically-ill children
Authors: Atis Seyma Koksal , Duyu Muhterem , Karakaya Zeynep , Yilmaz Alev
Published: March 2024

Bakcground

The aim of this study was to evaluate the efficacy and safety of citrate versus heparin anticoagulation for CRRT in critically-ill children.

Methods

This retrospective comparative cohort reviewed the clinical records of critically-ill children undergoing CRRT with either RCA or systemic heparin anticoagulation. The primary outcome measure was hemofilter survival time. Secondary outcomes included the comparison of complications and metabolic disorders.

Results

A total of 131 patients (55 RCA and 76 systemic heparin) were included, in which a cumulative number of 280 hemofilters were used (115 in RCA with 5762 h total CRRT time, and 165 in systemic heparin with 6230 h total CRRT time). Hemofilter survival was significantly longer for RCA (51.0 h; IQR: 24–67 h) compared to systemic heparin (29.5 h; IQR, 17–48 h) (p = 0.002). Clotting-related hemofilter failure occurred in 9.6% of the RCA group compared to 19.6% in the systemic heparin group (p = 0.038). Citrate accumulation occurred in 4 (3.5%) of 115 RCA sessions. Hypocalcemia and metabolic alkalosis episodes were significantly more frequent in RCA recipients (35.7% vs 15.2%, p < 0.0001; 33.0% vs 19.4%, p = 0.009).

Conclusion

RCA is a safe and effective anticoagulation method for CRRT in critically-ill children and it prolongs hemofilter survival.

Impact

RCA is superior to systemic heparin for the prolongation of circuit survival (overall and for clotting-related loss) during CRRT.

These data indicate that RCA can be used to maximize the effective delivery of CRRT in critically-ill patients admitted to the PICU.

There are potential cost-saving implications from our results owing to benefits such as less circuit downtime and fewer circuit changes.
Genetic and phenotypic similarity across major psychiatric disorders: a systematic review and quantitative assessment
Authors: Bourque Vincent-Raphael , Poulain Cécile , Proulx Catherine , Moreau Clara A. , Joober Ridha , Forgeot d’Arc Baudouin , Huguet Guillaume , Jacquemont Sébastien
Published: March 2024

There is widespread overlap across major psychiatric disorders, and this is the case at different levels of observations, from genetic variants to brain structures and function and to symptoms. However, it remains unknown to what extent these commonalities at different levels of observation map onto each other. Here, we systematically review and compare the degree of similarity between psychiatric disorders at all available levels of observation. We searched PubMed and EMBASE between January 1, 2009 and September 8, 2022. We included original studies comparing at least four of the following five diagnostic groups: Schizophrenia, Bipolar Disorder, Major Depressive Disorder, Autism Spectrum Disorder, and Attention Deficit Hyperactivity Disorder, with measures of similarities between all disorder pairs. Data extraction and synthesis were performed by two independent researchers, following the PRISMA guidelines. As main outcome measure, we assessed the Pearson correlation measuring the degree of similarity across disorders pairs between studies and biological levels of observation. We identified 2975 studies, of which 28 were eligible for analysis, featuring similarity measures based on single-nucleotide polymorphisms, gene-based analyses, gene expression, structural and functional connectivity neuroimaging measures. The majority of correlations (88.6%) across disorders between studies, within and between levels of observation, were positive. To identify a consensus ranking of similarities between disorders, we performed a principal component analysis. Its first dimension explained 51.4% (95% CI: 43.2, 65.4) of the variance in disorder similarities across studies and levels of observation. Based on levels of genetic correlation, we estimated the probability of another psychiatric diagnosis in first-degree relatives and showed that they were systematically lower than those observed in population studies. Our findings highlight that genetic and brain factors may underlie a large proportion, but not all of the diagnostic overlaps observed in the clinic.
Cannabinoid type 2 receptor inhibition enhances the antidepressant and proneurogenic effects of physical exercise after chronic stress
Authors: Rodrigues R. S. , Moreira J. B. , Mateus J. M. , Barateiro A. , Paulo S. L. , Vaz S. H. , Lourenço D. M. , Ribeiro F. F. , Soares R. , Loureiro-Campos E. , Bielefeld P. , Sebastião A. M. , Fernandes A. , Pinto L. , Fitzsimons C. P. , Xapelli S.
Published: March 2024

Chronic stress is a major risk factor for neuropsychiatric conditions such as depression. Adult hippocampal neurogenesis (AHN) has emerged as a promising target to counteract stress-related disorders given the ability of newborn neurons to facilitate endogenous plasticity. Recent data sheds light on the interaction between cannabinoids and neurotrophic factors underlying the regulation of AHN, with important effects on cognitive plasticity and emotional flexibility. Since physical exercise (PE) is known to enhance neurotrophic factor levels, we hypothesised that PE could engage with cannabinoids to influence AHN and that this would result in beneficial effects under stressful conditions. We therefore investigated the actions of modulating cannabinoid type 2 receptors (CB2R), which are devoid of psychotropic effects, in combination with PE in chronically stressed animals. We found that CB2R inhibition, but not CB2R activation, in combination with PE significantly ameliorated stress-evoked emotional changes and cognitive deficits. Importantly, this combined strategy critically shaped stress-induced changes in AHN dynamics, leading to a significant increase in the rates of cell proliferation and differentiation of newborn neurons, overall reduction in neuroinflammation, and increased hippocampal levels of BDNF. Together, these results show that CB2Rs are crucial regulators of the beneficial effects of PE in countering the effects of chronic stress. Our work emphasises the importance of understanding the mechanisms behind the actions of cannabinoids and PE and provides a framework for future therapeutic strategies to treat stress-related disorders that capitalise on lifestyle interventions complemented with endocannabinoid pharmacomodulation.
Oesophageal cancer awareness and anticipated time to help-seeking: results from a population-based survey
Authors: Sijben Jasmijn , Huibertse Lotte J. , Rainey Linda , Broeders Mireille J. M. , Peters Yonne , Siersema Peter D.
Published: March 2024

Background

Modifying public awareness of oesophageal cancer symptoms might help to decrease late-stage diagnosis and, in turn, improve cancer outcomes. This study aimed to explore oesophageal cancer symptom awareness and determinants of lower awareness and anticipated time to help-seeking.

Methods

We invited 18,156 individuals aged 18 to 75 years using random sampling of the nationwide Dutch population registry. A cross-sectional web-based survey containing items adapted from the Awareness and Beliefs about Cancer measure (i.e., cancer symptom awareness, anticipated time to presentation with dysphagia, health beliefs, and sociodemographic variables) was filled out by 3106 participants (response rate: 17%). Descriptive statistics were calculated and logistic regression analyses were performed to explore determinants of awareness and anticipated presentation (dichotomised as <1 month or ≥1 month).

Results

The number of participants that recognised dysphagia as a potential symptom of cancer was low (47%) compared with symptoms of other cancer types (change in bowel habits: 77%; change of a mole: 93%; breast lump: 93%). In multivariable analyses, non-recognition of dysphagia was associated with male gender (OR 0.50, 95% CI 0.43−0.58), lower education (OR 0.44, 0.35−0.54), and non-western migration background (OR 0.43, 0.28−0.67). Anticipated delayed help-seeking for dysphagia was associated with not recognising it as possible cancer symptom (OR 1.58, 1.27−1.97), perceived high risk of oesophageal cancer (OR 2.20, 1.39−3.47), and negative beliefs about oesophageal cancer (OR 1.86, 1.20−2.87).

Conclusion

Our findings demonstrate a disconcertingly low public awareness of oesophageal cancer symptoms. Educational interventions targeting groups with decreased awareness and addressing negative cancer beliefs may lead to faster help-seeking behaviour, although additional studies are needed to determine the effect on clinical cancer outcomes.
PCSK9 stimulates Syk, PKCδ, and NF-κB, leading to atherosclerosis progression independently of LDL receptor
Authors: Shin Dasom , Kim Soungchan , Lee Hwan , Lee Hyun-Chae , Lee Jaewon , Park Hyun-woo , Fukai Mina , Choi EunByule , Choi Subin , Koo Bon-Jun , Yu Ji-Hoon , No Gyurae , Cho Sungyoon , Kim Chan Woo , Han Dohyun , Jang Hyun-Duk , Kim Hyo-Soo
Published: March 2024

Proprotein convertase subtilisin/kexin type-9 (PCSK9) binds to and degrades low-density lipoprotein (LDL) receptor, leading to increase of LDL cholesterol in blood. Its blockers have emerged as promising therapeutics for cardiovascular diseases. Here we show that PCSK9 itself directly induces inflammation and aggravates atherosclerosis independently of the LDL receptor. PCSK9 exacerbates atherosclerosis in LDL receptor knockout mice. Adenylyl cyclase-associated protein 1 (CAP1) is the main binding partner of PCSK9 and indispensable for the inflammatory action of PCSK9, including induction of cytokines, Toll like receptor 4, and scavenger receptors, enhancing the uptake of oxidized LDL. We find spleen tyrosine kinase (Syk) and protein kinase C delta (PKCδ) to be the key mediators of inflammation after PCSK9-CAP1 binding. In human peripheral blood mononuclear cells, serum PCSK9 levels are positively correlated with Syk, PKCδ, and p65 phosphorylation. The CAP1-fragment crystallizable region (CAP1-Fc) mitigates PCSK9-mediated inflammatory signal transduction more than the PCSK9 blocking antibody evolocumab does.
PLMSearch: Protein language model powers accurate and fast sequence search for remote homology
Authors: Liu Wei , Wang Ziye , You Ronghui , Xie Chenghan , Wei Hong , Xiong Yi , Yang Jianyi , Zhu Shanfeng
Published: March 2024

Homologous protein search is one of the most commonly used methods for protein annotation and analysis. Compared to structure search, detecting distant evolutionary relationships from sequences alone remains challenging. Here we propose PLMSearch (Protein Language Model), a homologous protein search method with only sequences as input. PLMSearch uses deep representations from a pre-trained protein language model and trains the similarity prediction model with a large number of real structure similarity. This enables PLMSearch to capture the remote homology information concealed behind the sequences. Extensive experimental results show that PLMSearch can search millions of query-target protein pairs in seconds like MMseqs2 while increasing the sensitivity by more than threefold, and is comparable to state-of-the-art structure search methods. In particular, unlike traditional sequence search methods, PLMSearch can recall most remote homology pairs with dissimilar sequences but similar structures. PLMSearch is freely available at https://dmiip.sjtu.edu.cn/PLMSearch.
Optimal blade pitch control for enhanced vertical-axis wind turbine performance
Authors: Le Fouest Sébastien , Mulleners Karen
Published: March 2024

Vertical-axis wind turbines are great candidates to enable wind power extraction in urban and off-shore applications. Currently, concerns around turbine efficiency and structural integrity limit their industrial deployment. Flow control can mitigate these concerns. Here, we experimentally demonstrate the potential of individual blade pitching as a control strategy and explain the flow physics that yields the performance enhancement. We perform automated experiments using a scaled-down turbine model coupled to a genetic algorithm optimiser to identify optimal pitching kinematics at on- and off-design operating conditions. We obtain two sets of optimal pitch profiles that achieve a three-fold increase in power coefficient at both operating conditions compared to the non-actuated turbine and a 77% reduction in structure-threatening load fluctuations at off-design conditions. Based on flow field measurements, we uncover how blade pitching manipulates the flow structures to enhance performance. Our results can aid vertical-axis wind turbines increase their much-needed contribution to our energy needs.
A lineage-resolved cartography of microRNA promoter activity in C. elegans empowers multidimensional developmental analysis
Authors: Xu Weina , Liu Jinyi , Qi Huan , Si Ruolin , Zhao Zhiguang , Tao Zhiju , Bai Yuchuan , Hu Shipeng , Sun Xiaohan , Cong Yulin , Zhang Haoye , Fan Duchangjiang , Xiao Long , Wang Yangyang , Li Yongbin , Du Zhuo
Published: March 2024

Elucidating the expression of microRNAs in developing single cells is critical for functional discovery. Here, we construct scCAMERA (single-cell cartography of microRNA expression based on reporter assay), utilizing promoter-driven fluorescent reporters in conjunction with imaging and lineage tracing. The cartography delineates the transcriptional activity of 54 conserved microRNAs in lineage-resolved single cells throughout C. elegans embryogenesis. The combinatorial expression of microRNAs partitions cells into fine clusters reflecting their function and anatomy. Notably, the expression of individual microRNAs exhibits high cell specificity and divergence among family members. Guided by cellular expression patterns, we identify developmental functions of specific microRNAs, including miR-1 in pharynx development and physiology, miR-232 in excretory canal morphogenesis by repressing NHR-25/NR5A, and a functional synergy between miR-232 and miR-234 in canal development, demonstrating the broad utility of scCAMERA. Furthermore, integrative analysis reveals that tissue-specific fate determinants activate microRNAs to repress protein production from leaky transcripts associated with alternative, especially neuronal, fates, thereby enhancing the fidelity of developmental fate differentiation. Collectively, our study offers rich opportunities for multidimensional expression-informed analysis of microRNA biology in metazoans.
Myeloid-derived suppressor cell mitochondrial fitness governs chemotherapeutic efficacy in hematologic malignancies
Authors: Daneshmandi Saeed , Choi Jee Eun , Yan Qi , MacDonald Cameron R. , Pandey Manu , Goruganthu Mounika , Roberts Nathan , Singh Prashant K. , Higashi Richard M. , Lane Andrew N. , Fan Teresa W-M. , Wang Jianmin , McCarthy Philip L. , Repasky Elizabeth A. , Mohammadpour Hemn
Published: March 2024

Myeloid derived suppressor cells (MDSCs) are key regulators of immune responses and correlate with poor outcomes in hematologic malignancies. Here, we identify that MDSC mitochondrial fitness controls the efficacy of doxorubicin chemotherapy in a preclinical lymphoma model. Mechanistically, we show that triggering STAT3 signaling via β2-adrenergic receptor (β2-AR) activation leads to improved MDSC function through metabolic reprograming, marked by sustained mitochondrial respiration and higher ATP generation which reduces AMPK signaling, altering energy metabolism. Furthermore, induced STAT3 signaling in MDSCs enhances glutamine consumption via the TCA cycle. Metabolized glutamine generates itaconate which downregulates mitochondrial reactive oxygen species via regulation of Nrf2 and the oxidative stress response, enhancing MDSC survival. Using β2-AR blockade, we target the STAT3 pathway and ATP and itaconate metabolism, disrupting ATP generation by the electron transport chain and decreasing itaconate generation causing diminished MDSC mitochondrial fitness. This disruption increases the response to doxorubicin and could be tested clinically.
Ultrastable halide perovskite CsPbBr3 photoanodes achieved with electrocatalytic glassy-carbon and boron-doped diamond sheets
Authors: Zhu Zhonghui , Daboczi Matyas , Chen Minzhi , Xuan Yimin , Liu Xianglei , Eslava Salvador
Published: March 2024

Halide perovskites exhibit exceptional optoelectronic properties for photoelectrochemical production of solar fuels and chemicals but their instability in aqueous electrolytes hampers their application. Here we present ultrastable perovskite CsPbBr3-based photoanodes achieved with both multifunctional glassy carbon and boron-doped diamond sheets coated with Ni nanopyramids and NiFeOOH. These perovskite photoanodes achieve record operational stability in aqueous electrolytes, preserving 95% of their initial photocurrent density for 168 h of continuous operation with the glassy carbon sheets and 97% for 210 h with the boron-doped diamond sheets, due to the excellent mechanical and chemical stability of glassy carbon, boron-doped diamond, and nickel metal. Moreover, these photoanodes reach a low water-oxidation onset potential close to +0.4 VRHE and photocurrent densities close to 8 mA cm−2 at 1.23 VRHE, owing to the high conductivity of glassy carbon and boron-doped diamond and the catalytic activity of NiFeOOH. The applied catalytic, protective sheets employ only earth-abundant elements and straightforward fabrication methods, engineering a solution for the success of halide perovskites in stable photoelectrochemical cells.
Magnetic field filtering of the boundary supercurrent in unconventional metal NiTe2-based Josephson junctions
Authors: Le Tian , Zhang Ruihan , Li Changcun , Jiang Ruiyang , Sheng Haohao , Tu Linfeng , Cao Xuewei , Lyu Zhaozheng , Shen Jie , Liu Guangtong , Liu Fucai , Wang Zhijun , Lu Li , Qu Fanming
Published: March 2024

Topological materials with boundary (surface/edge/hinge) states have attracted tremendous research interest. Additionally, unconventional (obstructed atomic) materials have recently drawn lots of attention owing to their obstructed boundary states. Experimentally, Josephson junctions (JJs) constructed on materials with boundary states produce the peculiar boundary supercurrent, which was utilized as a powerful diagnostic approach. Here, we report the observations of boundary supercurrent in NiTe2-based JJs. Particularly, applying an in-plane magnetic field along the Josephson current can rapidly suppress the bulk supercurrent and retain the nearly pure boundary supercurrent, namely the magnetic field filtering of supercurrent. Further systematic comparative analysis and theoretical calculations demonstrate the existence of unconventional nature and obstructed hinge states in NiTe2, which could produce hinge supercurrent that accounts for the observation. Our results reveal the probable hinge states in unconventional metal NiTe2, and demonstrate in-plane magnetic field as an efficient method to filter out the bulk contributions and thereby to highlight the hinge states hidden in topological/unconventional materials.