bluuebunny/crossref_metadata_2025 huggingface dataset:
State of soil fertility in Lviv Region
Authors: Zaitsev Yu. , Demchyshyn A. , Gunchak M.
Published: May 2023

The main indicators of soil fertility based on the results of an agrochemical survey of agricultural lands of Lviv region in the XI round (2016–2020) are given. It was established that the acidity of the soil solution in the region is dominated by lands with a neutral reaction of the soil solution (31.3%). The weighted average indicator of saline pH is 6.0, which corresponds to a close to neutral reaction of the soil solution. According to the level of humus provision, soils with an average humus content prevail (36.1%) and the weighted average humus content in the region is 2.6%. According to the content of easily hydrolyzable nitrogen, most of the lands have a low (60.4%) and medium nitrogen content (18.0%). The weighted average indicator of easily hydrolyzable nitrogen content for the reporting period is 125.6 mg/kg of soil, which corresponds to the low availability of this element. The region is dominated by lands with increased (25.1%) and high content of mobile phosphorus compounds (25.3%) and the weighted average indicator of the content of mobile phosphorus compounds is 107.2 mg/kg, which corresponds to increased availability. In terms of the content of mobile potassium compounds, lands with average potassium content (30.3%) prevail and the weighted average indicator of the content of mobile potassium compounds is 72.2 mg/kg, which corresponds to the average supply with macro element. It was established that in Lviv region, the largest area is occupied by soils of average quality (52.2%), and the average weighted assessment of agricultural land in Lviv region is 43. A comparison of the qualitative assessment of the soils of Lviv region for the X (2011–2015) and XI rounds (2016–2020) of agrochemical examinations is carried out. The results established that the quality of the soils in the Starosambir, Mostysky, Radekhiv and Drohobytsky districts has hardly changed. The quality assessment of the soils of Busky, Zhovkivskyi, Kamianka-Buskyi and Sokalskyi districts improved by 2–4 points, the qualitative assessment of the land condition of Peremyshlyanskyi, Zolochivskyi and Yavorivskyi districts improved by 7-19 points. A decrease in land quality indicators by 2-5 points was recorded in Brodivskyi, Pustomytivskyi, Sambirskyi and Stryiskyi districts, indicators of the qualitative assessment of land condition in Zhydachivskyi and Mykolaivskyi districts worsened by 12-13 points.
Trained innate immunity, epigenetics, and food allergy
Authors: Arzola-Martínez Llilian , Ptaschinski Catherine , Lukacs Nicholas W.
Published: May 2023

In recent years the increased incidence of food allergy in Western culture has been associated with environmental factors and an inappropriate immune phenotype. While the adaptive immune changes in food allergy development and progression have been well-characterized, an increase in innate cell frequency and activation status has also recently received greater attention. Early in prenatal and neonatal development of human immunity there is a reliance on epigenetic and metabolic changes that stem from environmental factors, which are critical in training the immune outcomes. In the present review, we discuss how trained immunity is regulated by epigenetic, microbial and metabolic factors, and how these factors and their impact on innate immunity have been linked to the development of food allergy. We further summarize current efforts to use probiotics as a potential therapeutic approach to reverse the epigenetic and metabolic signatures and prevent the development of severe anaphylactic food allergy, as well as the potential use of trained immunity as a diagnostic and management strategy. Finally, trained immunity is presented as one of the mechanisms of action of allergen-specific immunotherapy to promote tolerogenic responses in allergic individuals.
Formulation of pH-responsive highly swellable hydrogel scaffolds for controlled release of tramadol HCl: characterization and biocompatibility evaluation
Authors: Abdullah Zainab , Ashraf Muhammad Umer , Barkat Kashif , Badshah Syed Faisal , Rehman Umaira , Razzaq Asma , Mahmood Asif , Ulhaq Farid , Chopra Hitesh , Rashid Summya , Valko Marian , Alomar Suliman , Kuca Kamil , Sharma Rohit
Published: May 2023

Introduction: The objective of current project was to formulate a system for controlled delivery of Tramadol HCl (TRD), an opioid analgesic used in the treatment of moderate to severe pain.

Methods: For this purpose, a pH responsive AvT-co-poly hydrogel network was formulated through free radical polymerization by incorporating natural polymers i.e., aloe vera gel and tamarind gum, monomer and crosslinker. Formulated hydrogels were loaded with Tramadol HCl (TRD) and evaluated for percent drug loading, sol-gel fraction, dynamic and equilibrium swelling, morphological characteristics, structural features and in-vitro release of Tramadol HCl.

Results and Discussions: Hydrogels were proved to be pH sensitive as remarkable dynamic swelling response ranging within 2.94g/g-10.81g/g was noticed at pH 7.4 as compared to pH 1.2. Percent drug loading was in the range of 70.28%-90.64% for all formulations. Thermal stability and compatibility of hydrogel components were validated by DSC analysis and FTIR spectroscopy. Controlled release pattern of Tramadol HCl from the polymeric network was confirmed as maximum release of 92.22% was observed for over a period of 24 hours at pH 7.4. Moreover, oral toxicity studies were also conducted in rabbits to investigate the safety of hydrogels. No evidence of any toxicity, lesions and degeneration was reported, confirming the biocompatibility and safety of grafted system.
OpenCL-accelerated first-principles calculations of all-electron quantum perturbations on HPC resources
Authors: Wu Zhikun , Shang Honghui , Wu Yangjun , Zhang Zhongcheng , Liu Ying , Zhang Yuyang , Ouyang Yucheng , Cui Huimin , Feng Xiaobing
Published: May 2023

We have proposed, for the first time, an OpenCL implementation for the all-electron density-functional perturbation theory (DFPT) calculations in FHI-aims, which can effectively compute all its time-consuming simulation stages, i.e., the real-space integration of the response density, the Poisson solver for the calculation of the electrostatic potential, and the response Hamiltonian matrix, by utilizing various heterogeneous accelerators. Furthermore, to fully exploit the massively parallel computing capabilities, we have performed a series of general-purpose graphics processing unit (GPGPU)-targeted optimizations that significantly improved the execution efficiency by reducing register requirements, branch divergence, and memory transactions. Evaluations on the Sugon supercomputer have shown that notable speedups can be achieved across various materials.
Novel systems to study vector-pathogen interactions in malaria
Authors: Parres-Mercader Marina , Pance Alena , Gómez-Díaz Elena
Published: May 2023

Some parasitic diseases, such as malaria, require two hosts to complete their lifecycle: a human and an insect vector. Although most malaria research has focused on parasite development in the human host, the life cycle within the vector is critical for the propagation of the disease. The mosquito stage of the Plasmodium lifecycle represents a major demographic bottleneck, crucial for transmission blocking strategies. Furthermore, it is in the vector, where sexual recombination occurs generating “de novo” genetic diversity, which can favor the spread of drug resistance and hinder effective vaccine development. However, understanding of vector-parasite interactions is hampered by the lack of experimental systems that mimic the natural environment while allowing to control and standardize the complexity of the interactions. The breakthrough in stem cell technologies has provided new insights into human-pathogen interactions, but these advances have not been translated into insect models. Here, we review in vivo and in vitro systems that have been used so far to study malaria in the mosquito. We also highlight the relevance of single-cell technologies to progress understanding of these interactions with higher resolution and depth. Finally, we emphasize the necessity to develop robust and accessible ex vivo systems (tissues and organs) to enable investigation of the molecular mechanisms of parasite-vector interactions providing new targets for malaria control.
Molecular characterization of Smtdc-1 and Smddc-1 discloses roles as male-competence factors for the sexual maturation of Schistosoma mansoni females
Authors: Li Xuesong , Weth Oliver , Haeberlein Simone , Grevelding Christoph G.
Published: May 2023

Introduction

Schistosomes are the only mammalian flatworms that have evolved separate sexes. A key question of schistosome research is the male-dependent sexual maturation of the female since a constant pairing contact with a male is required for the onset of gonad development in the female. Although this phenomenon is long known, only recently a first peptide-based pheromone of males was identified that contributes to the control of female sexual development. Beyond this, our understanding of the molecular principles inducing the substantial developmental changes in a paired female is still rudimentary.

Objectives

Previous transcriptomic studies have consistently pointed to neuronal genes being differentially expressed and upregulated in paired males. These genes included Smp_135230 and Smp_171580, both annotated as aromatic-L-amino-acid decarboxylases (DOPA decarboxylases). Here, we characterized both genes and investigated their roles in male–female interaction of S. mansoni.

Methodologies/findings

Sequence analyses indicated that Smp_135230 represents an L-tyrosine decarboxylase (Smtdc-1), whereas Smp_171580 represents a DOPA decarboxylase (Smddc-1). By qRT-PCR, we confirmed the male-specific and pairing-dependent expression of both genes with a significant bias toward paired males. RNA-interference experiments showed a strong influence of each gene on gonad differentiation in paired females, which was enhanced by double knockdown. Accordingly, egg production was significantly reduced. By confocal laser scanning microscopy, a failure of oocyte maturation was found in paired knockdown females. Whole-mount in situ hybridization patterns exhibited the tissue-specific occurrence of both genes in particular cells at the ventral surface of the male, the gynecophoral canal, which represents the physical interface of both genders. These cells probably belong to the predicted neuronal cluster 2 of S. mansoni.

Conclusion

Our results suggest that Smtdc-1 and Smddc-2 are male-competence factors that are expressed in neuronal cells at the contact zone between the genders as a response of pairing to subsequently control processes of female sexual maturation.
Examining perceptions of a telemedicine network for pediatric emergency medicine: a mixed-methods pilot study
Authors: Mateus Lidia A. , Law Madelyn P. , Khowaja Asif Raza , Orlando Elaina , Pace Alexander , Roy Madan , Sulowski Christopher
Published: May 2023

Background

Use of telemedicine for healthcare delivery in the emergency department can increase access to specialized care for pediatric patients without direct access to a children's hospital. Currently, telemedicine is underused in this setting.

Objectives

This pilot research project aimed to evaluate the perceived effectiveness of a telemedicine program in delivering care to critically ill pediatric patients in the emergency department by exploring the experiences of parents/caregivers and physicians.

Methods

Sequential explanatory mixed methods were employed, in which quantitative methods of inquiry were followed by qualitative methods. Data were collected through a post-used survey for physicians, followed by semi-structured interviews with physicians and parents/guardians of children treated through the program. Descriptive statistics were used to analyze the survey data. Reflexive thematic analysis was used to analyze interview data.

Results

The findings describe positive perceptions of telemedicine for emergency department pediatric care, as well as barriers and facilitators to its use. The research also discusses implications for practice and recommendations for overcoming barriers and supporting facilitators when implementing telemedicine programming.

Conclusion

The findings suggest that a telemedicine program has utility and acceptance among parents/caregivers and physicians for the treatment of critically ill pediatric patients in the emergency department. Benefits recognized and valued by both parents/caregivers and physicians include rapid connection to sub-specialized care and enhanced communication between remote and local physicians. Sample size and response rate are key limitations of the study.
Upper crust anisotropy of the 2020 Jiashi MS 6.4 earthquake
Authors: Li Jin , Gao Yuan , Zhou Shaohui
Published: May 2023

The 2020 Jiashi MS 6.4 earthquake occurred north of the 1997–1998 Jiashi earthquake swarm. Because of its complex tectonic environment and frequent strong earthquake occurrence, scholars have paid extensive attention to this area. To study the upper crustal anisotropy in the source area, we applied microseismic event detection and shear-wave splitting techniques to the seismic data recorded by five stations around the epicenter. First, the earthquake catalog of the Jiashi MS 6.4 earthquake sequence was rebuilt using the “Match & Locate” method. A total of 9,695 earthquake events were obtained, and the number of newly detected earthquakes was approximately 7.3 times the number in the officially released catalog. The newly identified microseismic data greatly increased the number of effective records and improved the reliability of the results. We analyzed shear-wave splitting according to the updated catalog. The results showed that the dominant polarizations of the fast shear waves were in NW or NNW at the stations BPM, XKR, L6505, and L6513, consistent with the stress near the source area. There are also blind faults with an NNW direction in the strike distributing en echelon and parallel to the main stress direction in the Jiashi seismic area. Thus, the fast shear-wave polarization of the four stations may also reflect the strike of multiple buried NNW faults in the study area. The fast shear-wave polarization of station HLJ, located at the Halajun Basin, was E–W, with the overall trend of the Kalpin thrust nappe structure. However, this station didn’t show the same NW or NNW fast-wave direction as the four stations previously mentioned. This finding may indicate that the NW-trending buried faults in the Jiashi seismic area have a limited size in both the length and the depth, only reaching northward near the second row of the Kapingtag nappe structure. The temporal trend of the delay time at station HLJ showed that a stress-release process occurred before the MS 6.4 earthquake and that stress-release occurred again after the mainshock. At station XKR, the delay time rapidly increased and then fell in the early period after the MS 6.4 earthquake, indicating that stress accumulated rapidly after the main earthquake but was released during the aftershock sequence. This study provides novel insights into the complex structural characteristics and seismogenic environment in the Jiashi area.
Nomogram prediction for cervical lymph node metastasis in multifocal papillary thyroid microcarcinoma
Authors: Li Wen-Hui , Yu Wei-Ying , Du Jia-Rui , Teng Deng-Ke , Lin Yuan-Qiang , Sui Guo-Qing , Wang Hui
Published: May 2023

Aim

Accurate preoperative prediction of cervical lymph node metastasis (LNM) in patients with mPTMC provides a basis for surgical decision making and the extent of tumor resection. This study aimed to develop and validate an ultrasound radiomics nomogram for the preoperative assessment of LN status.

Methods

A total of 450 patients pathologically diagnosed with mPTMC were enrolled, including 348 patients in the modeling group and 102 patients in the validation group. Univariate and multivariate logistic regression analyses were performed on the basic information, ultrasound characteristics, and American College of Radiology Thyroid Imaging Reporting and Data System (ACR TI-RADS) scores of the patients in the modeling group to identify independent risk factors for LNM in mPTMC and to construct a logistic regression equation and nomogram to predict the risk of LNM. The validation group data were used to evaluate the predictive performance of the nomogram.

Results

Male sex, age <40 years, a single lesion with a maximum diameter >0.5 cm, capsular invasion, a maximum ACR score >9 points, and a total ACR score >19 points were independent risk factors for the development of cervical LNM in mPTMC. Both the area under the curve (AUC) and concordance index (C-index) of the prediction model constructed from the above six factors were 0.838. The calibration curve of the nomogram was close to the ideal diagonal line. Furthermore, decision curve analysis (DCA) demonstrated a significantly greater net benefit of the model. The external validation demonstrated the reliability of the prediction nomogram.

Conclusions

The presented radiomics nomogram, which is based on ACR TI-RADS scores, shows favorable predictive value for the preoperative assessment of LNs in patients with mPTMC. These findings may provide a basis for surgical decision making and the extent of tumor resection.
Association of growth hormone deficiency with an increased number of preadipocytes in subcutaneous fat
Authors: Zhao Lidan , Jia Dan , Tan Zhendong , Jiang Honglin
Published: May 2023

The inhibitory effect of growth hormone (GH) on adipose tissue growth is well known, but the underlying mechanism is not fully understood. In this study, we determined the possibility that GH inhibits adipose tissue growth by inhibiting adipogenesis, the process of formation of adipocytes from stem cells, in the lit/lit mice. The lit/lit mice are GH deficient because of a spontaneous mutation to the GH releasing hormone receptor (ghrhr) gene, and they have more subcutaneous fat despite being smaller than the lit/+ mice at the same age. We found that cells of the stromal vascular fraction (SVF) of subcutaneous fat from the lit/lit mice had greater adipogenic potential than those from the lit/+ mice, as evidenced by forming greater numbers of lipid droplets-containing adipocytes and having greater expression of adipocyte marker genes during induced adipocyte differentiation in culture. However, addition of GH to the culture did not reverse the superior adipogenic potential of subcutaneous SVF from the lit/lit mice. Through florescence-activated cell sorting and quantification of mRNAs of preadipocyte markers, including CD34, CD29, Sca-1, CD24, Pref-1, and PPARγ, we found that subcutaneous SVF from the lit/lit mice contained more preadipocytes than that from the lit/+ mice. These results support the notion that GH inhibits adipose tissue growth in mice at least in part by inhibiting adipogenesis. Furthermore, these results suggest that GH inhibits adipogenesis in mice not by inhibiting the terminal differentiation of preadipocytes into adipocytes, rather by inhibiting the formation of preadipocytes from stem cells or the recruitment of stem cells to the fat depot.
Electric vehicle charging path planning considering couped faults in distribution-transportation network
Authors: Fu Wanxin , Wei Minjie
Published: May 2023

Once a distribution network failure occurs, it can spread to the traffic network through the coupling point, causing electric vehicles (EVs) to change their charging paths. To address this problem, this paper presents an EV charging path planning approach that considers coupled faults in the distribution-transportation network. First, the cascading failure model of the distribution-transportation network and the model for choosing charging stations are presented to transfer the information of coupling faults propagation and coupling points power interaction to the follow-up path planning scheme. Second, a time occupancy road resistance model that considers congested and unobstructed traffic states is proposed to calculate the road section travel time, based on the analysis results of the evolution process of road traffic flow queuing using traffic wave theory. For the speed and density parameters in the traffic wave model, values are calculated using the logistics speed-density model and the time occupancy model. Third, a multi-objective optimization function that integrates travel cost and coupling network operation state is determined from the perspective of hindering the propagation of coupling faults. The function is solved to recommend optimal charging paths using an improved A* searching algorithm. Finally, a 90-bus road network and three 33-bus distribution networks are selected as examples to verify the veracity and validity of the proposed model and method. The research results demonstrate that the proposed method can alleviate traffic congestion.
Soil fertility and landscape surrounding former arable fields drive the ecological resilience of Mediterranean dry grassland plant communities
Authors: Jaunatre Renaud , Buisson Elise , Leborgne Elsa , Dutoit Thierry
Published: May 2023

Introduction

Semi-natural dry grasslands are among the species-richest and most diverse habitats in Europe especially in the Mediterranean Basin. They evolved with long-term severe environmental constraints, either biotic (e.g., grazing or mowing) or abiotic (e.g., dryness or oligotrophy). Their recovery after sever anthropogenic disturbance, such as cultivation is often very slow and incomplete. A deeper understanding of the processes driving the recovery would be of great benefit to better restore or conserve these grasslands. We used the filter model as a framework to assess the relative importance of dispersion, abiotic and biotic filters as drivers of this recovery.

Methods

We studied the medium-term dynamics of 37 Mediterranean dry grassland plant communities after an episode of cultivation in the plain of La Crau (Southern France) by two census: after 25 years of abandonment, and revisited 10 years later (35 years of abandonment). Our aims were to characterize the temporal medium-term dynamics of these communities, to measure their taxonomic resilience and to identify the drivers. We performed structural equation modeling to measure the importance of the various drivers, with cover of remnant dry grasslands surrounding each studied community as a proxy for the dispersion filter, soil pH and phosphorus content as proxies for the abiotic filter and cover of the most dominant species as a proxy for the biotic filter.

Results and Discussion

Our results show that former arable field vegetation do not recover after more than 40 years. The three filters drive the recovery of dry grassland vegetation: former arable fields that have lower phosphorus content (abiotic filter) have a lower cover of dominant species (biotic filter), a higher species richness and a higher similarity with remnant dry grassland plant communities, especially if the former arable fields are surrounded by remnant dry grasslands (dispersion filter).
Facilitating systems-level analyses of all-cause and Covid-mediated sepsis through SeptiSearch, a manually-curated compendium of dysregulated gene sets
Authors: Baghela Arjun S. , Tam Jasmine , Blimkie Travis M. , Dhillon Bhavjinder K. , Hancock Robert E.W.
Published: May 2023

Background

Sepsis is a dysfunctional host response to infection. The syndrome leads to millions of deaths annually (19.7% of all deaths in 2017) and is the cause of most deaths from severe Covid infections. High throughput sequencing or ‘omics’ experiments in molecular and clinical sepsis research have been widely utilized to identify new diagnostics and therapies. Transcriptomics, quantifying gene expression, has dominated these studies, due to the efficiency of measuring gene expression in tissues and the technical accuracy of technologies like RNA-Seq.

Objective

Most of these studies seek to uncover novel mechanistic insights into sepsis pathogenesis and diagnostic gene signatures by identifying genes differentially expressed between two or more relevant conditions. However, little effort has been made, to date, to aggregate this knowledge from such studies. In this study we sought to build a compendium of previously described gene sets that combines knowledge gained from sepsis-associated studies. This would enable the identification of genes most associated with sepsis pathogenesis, and the description of the molecular pathways commonly associated with sepsis.

Methods

PubMed was searched for studies using transcriptomics to characterize acute infection/sepsis and severe sepsis (i.e., sepsis combined with organ failure). Several studies were identified that used transcriptomics to identify differentially expressed (DE) genes, predictive/prognostic signatures, and underlying molecular responses and pathways. The molecules included in each gene set were collected, in addition to the relevant study metadata (e.g., patient groups used for comparison, sample collection time point, tissue type, etc.).

Results

After performing extensive literature curation of 74 sepsis-related publications involving transcriptomics, 103 unique gene sets (comprising 20,899 unique genes) from thousands of patients were collated together with associated metadata. Frequently described genes included in gene sets as well as the molecular mechanisms they were involved in were identified. These mechanisms included neutrophil degranulation, generation of second messenger molecules, IL-4 and -13 signaling, and IL-10 signaling among many others. The database, which we named SeptiSearch, is made available in a web application created using the Shiny framework in R, (available at https://septisearch.ca).

Conclusions

SeptiSearch provides members of the sepsis community the bioinformatic tools needed to leverage and explore the gene sets contained in the database. This will allow the gene sets to be further scrutinized and analyzed for their enrichment in user-submitted gene expression data and used for validation of in-house gene sets/signatures.
Sex and gender influence on immunity and autoimmunity
Authors: Lahita Robert G.
Published: May 2023

Autoimmune diseases are skewed toward one biological sex or another. This is the obvious observation of many decades, and it remains unexplained. Females predominate with most autoimmune diseases. The reasons for this predilection are an interplay of genetic, epigenetic and hormonal factors.
Variable resistance to zinc intoxication among Streptococcus agalactiae reveals a novel IS1381 insertion element within the zinc efflux transporter gene czcD
Authors: Varghese Brian R. , Goh Kelvin G. K. , Desai Devika , Acharya Dhruba , Chee Collin , Sullivan Matthew J. , Ulett Glen C.
Published: May 2023

Streptococcus agalactiae, also known as group B Streptococcus, is an important human and animal pathogen. Zinc (Zn) is an essential trace element for normal bacterial physiology but intoxicates bacteria at high concentrations. Molecular systems for Zn detoxification exist in S. agalactiae, however the degree to which Zn detoxification may vary among different S. agalactiae isolates is not clear. We measured resistance to Zn intoxication in a diverse collection of clinical isolates of S. agalactiae by comparing the growth of the bacteria in defined conditions of Zn stress. We found significant differences in the ability of different S. agalactiae isolates to resist Zn intoxication; some strains such as S. agalactiae 18RS21 were able to survive and grow at 3.8-fold higher levels of Zn stress compared to other reference strains such as BM110 (6.4mM vs 1.68mM Zn as inhibitory, respectively). We performed in silico analysis of the available genomes of the S. agalactiae isolates used in this study to examine the sequence of czcD, which encodes an efflux protein for Zn that supports resistance in S. agalactiae. Interestingly, this revealed the presence of a mobile insertion sequence (IS) element, termed IS1381, in the 5′ region of czcD in S. agalactiae strain 834, which was hyper-resistant to Zn intoxication. Interrogating a wider collection of S. agalactiae genomes revealed identical placement of IS1381 in czcD in other isolates from the clonal-complex-19 (CC19) 19 lineage. Collectively, these results show a resistance spectrum among S. agalactiae isolates enables survival in varying degrees of Zn stress, and this phenotypic variability has implications for understanding bacterial survival in metal stress.
Tocilizumab versus anakinra in COVID-19: results from propensity score matching
Authors: Arcani Robin , Correard Florian , Suchon Pierre , Kaplanski Gilles , Jean Rodolphe , Cauchois Raphael , Leprince Marine , Arcani Vincent , Seguier Julie , De Sainte Marie Benjamin , Andre Baptiste , Koubi Marie , Rossi Pascal , Gayet Stéphane , Gobin Nirvina , Garrido Victoria , Weiland Joris , Jouve Elisabeth , Couderc Anne-Laure , Villani Patrick , Daumas Aurélie
Published: May 2023

Background

Tocilizumab and anakinra are anti-interleukin drugs to treat severe coronavirus disease 2019 (COVID-19) refractory to corticosteroids. However, no studies compared the efficacy of tocilizumab versus anakinra to guide the choice of the therapy in clinical practice. We aimed to compare the outcomes of COVID-19 patients treated with tocilizumab or anakinra.

Methods

Our retrospective study was conducted in three French university hospitals between February 2021 and February 2022 and included all the consecutive hospitalized patients with a laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection assessed by RT-PCR who were treated with tocilizumab or anakinra. A propensity score matching was performed to minimize confounding effects due to the non-random allocation.

Results

Among 235 patients (mean age, 72 years; 60.9% of male patients), the 28-day mortality (29.4% vs. 31.2%, p = 0.76), the in-hospital mortality (31.7% vs. 33.0%, p = 0.83), the high-flow oxygen requirement (17.5% vs. 18.3%, p = 0.86), the intensive care unit admission rate (30.8% vs. 22.2%, p = 0.30), and the mechanical ventilation rate (15.4% vs. 11.1%, p = 0.50) were similar in patients receiving tocilizumab and those receiving anakinra. After propensity score matching, the 28-day mortality (29.1% vs. 30.4%, p = 1) and the rate of high-flow oxygen requirement (10.1% vs. 21.5%, p = 0.081) did not differ between patients receiving tocilizumab or anakinra. Secondary infection rates were similar between the tocilizumab and anakinra groups (6.3% vs. 9.2%, p = 0.44).

Conclusion

Our study showed comparable efficacy and safety profiles of tocilizumab and anakinra to treat severe COVID-19.
An iterative labeling method for annotating marine life imagery
Authors: Zhang Zhiyong , Kaveti Pushyami , Singh Hanumant , Powell Abigail , Fruh Erica , Clarke M. Elizabeth
Published: May 2023

This paper presents a labeling methodology for marine life data using a weakly supervised learning framework. The methodology iteratively trains a deep learning model using non-expert labels obtained from crowdsourcing. This approach enables us to converge on a labeled image dataset through multiple training and production loops that leverage crowdsourcing interfaces. We present our algorithm and its results on two separate sets of image data collected using the Seabed autonomous underwater vehicle. The first dataset consists of 10,505 images that were point annotated by NOAA biologists. This dataset allows us to validate the accuracy of our labeling process. We also apply our algorithm and methodology to a second dataset consisting of 3,968 completely unlabeled images. These image categories are challenging to label, such as sponges. Qualitatively, our results indicate that training with a tiny subset and iterating on those results allows us to converge to a large, highly annotated dataset with a small number of iterations. To demonstrate the effectiveness of our methodology quantitatively, we tabulate the mean average precision (mAP) of the model as the number of iterations increases.
Biochemical composition and reproductive cycle of the clam Chamelea gallina in the Northern Adriatic Sea: an after-10-year comparison of patterns and changes
Authors: Moschino Vanessa , Rizzo Giulia , Marĉeta Tihana , Cernigai Federica , Masiero Luciano , Da Ros Luisa , Marin Maria Gabriella
Published: May 2023

The study of the relationships between growth patterns, energy reserves and reproduction, and their interdependency with environmental variables is crucial to increase the knowledge of the physiological processes regulating the recruitment and survival of commercially exploited bivalve species. In the present study, the biochemical profile and gametogenic cycle of the striped Venus clam Chamelea gallina monthly sampled in fishing grounds of the Chioggia district in 2001 and 2010 were investigated to identify possible variations that occurred after 10 years and to analyze inter-relationships among the biological parameters with changing environmental conditions. Our results indicated that higher phytoplankton availability and increased water temperature recorded from 2001 to 2010 resulted in higher reserve accumulation, mostly in the form of proteins, carbohydrates and glycogen. An increase was also observed in the calcification rate of the shells, which consequently became heavier in clams collected in 2010. Moreover, in 2010, as for the reproductive conditions, a prolonged spawning period was observed with respect to 2002. Overall results highlighted clear-cut differences in the physiological performances of clams collected in 2001 and 2010, suggesting the importance to monitor changes over time to unveil potential pros and cons for single populations of commercial interest.
Predicting omicron pneumonia severity and outcome: a single-center study in Hangzhou, China
Authors: Xu Jingjing , Cao Zhengye , Miao Chunqin , Zhang Minming , Xu Xiaojun
Published: May 2023

Background

In December 2022, there was a large Omicron epidemic in Hangzhou, China. Many people were diagnosed with Omicron pneumonia with variable symptom severity and outcome. Computed tomography (CT) imaging has been proven to be an important tool for COVID-19 pneumonia screening and quantification. We hypothesized that CT-based machine learning algorithms can predict disease severity and outcome in Omicron pneumonia, and we compared its performance with the pneumonia severity index (PSI)-related clinical and biological features.

Methods

Our study included 238 patients with the Omicron variant who have been admitted to our hospital in China from 15 December 2022 to 16 January 2023 (the first wave after the dynamic zero-COVID strategy stopped). All patients had a positive real-time polymerase chain reaction (PCR) or lateral flow antigen test for SARS-CoV-2 after vaccination and no previous SARS-CoV-2 infections. We recorded patient baseline information pertaining to demographics, comorbid conditions, vital signs, and available laboratory data. All CT images were processed with a commercial artificial intelligence (AI) algorithm to obtain the volume and percentage of consolidation and infiltration related to Omicron pneumonia. The support vector machine (SVM) model was used to predict the disease severity and outcome.

Results

The receiver operating characteristic (ROC) area under the curve (AUC) of the machine learning classifier using PSI-related features was 0.85 (accuracy = 87.40%, p < 0.001) for predicting severity while that using CT-based features was only 0.70 (accuracy = 76.47%, p = 0.014). If combined, the AUC was not increased, showing 0.84 (accuracy = 84.03%, p < 0.001). Trained on outcome prediction, the classifier reached the AUC of 0.85 using PSI-related features (accuracy = 85.29%, p < 0.001), which was higher than using CT-based features (AUC = 0.67, accuracy = 75.21%, p < 0.001). If combined, the integrated model showed a slightly higher AUC of 0.86 (accuracy = 86.13%, p < 0.001). Oxygen saturation, IL-6, and CT infiltration showed great importance in both predicting severity and outcome.

Conclusion

Our study provided a comprehensive analysis and comparison between baseline chest CT and clinical assessment in disease severity and outcome prediction in Omicron pneumonia. The predictive model accurately predicts the severity and outcome of Omicron infection. Oxygen saturation, IL-6, and infiltration in chest CT were found to be important biomarkers. This approach has the potential to provide frontline physicians with an objective tool to manage Omicron patients more effectively in time-sensitive, stressful, and potentially resource-constrained environments.
Dysfunction of inhibitory interneurons contributes to synaptic plasticity via GABABR-pNR2B signaling in a chronic migraine rat model
Authors: Zeng Xiaoxu , Niu Yingying , Qin Guangcheng , Zhang Dunke , Chen Lixue
Published: May 2023

Background

According to our previous study, the loss of inhibitory interneuron function contributes to central sensitization in chronic migraine (CM). Synaptic plasticity is a vital basis for the occurrence of central sensitization. However, whether the decline in interneuron-mediated inhibition promotes central sensitization by regulating synaptic plasticity in CM remains unclear. Therefore, this study aims to explore the role of interneuron-mediated inhibition in the development of synaptic plasticity in CM.

Methods

A CM model was established in rats by repeated dural infusion of inflammatory soup (IS) for 7 days, and the function of inhibitory interneurons was then evaluated. After intraventricular injection of baclofen [a gamma-aminobutyric acid type B receptor (GABABR) agonist] or H89 [a protein kinase A (PKA) inhibitor), behavioral tests were performed. The changes in synaptic plasticity were investigated by determining the levels of the synapse-associated proteins postsynaptic density protein 95 (PSD95), synaptophysin (Syp) and synaptophysin-1(Syt-1)]; evaluating the synaptic ultrastructure by transmission electron microscopy (TEM); and determining the density of synaptic spines via Golgi-Cox staining. Central sensitization was evaluated by measuring calcitonin gene-related peptide (CGRP), brain-derived neurotrophic factor (BDNF), c-Fos and substance P (SP) levels. Finally, the PKA/Fyn kinase (Fyn)/tyrosine-phosphorylated NR2B (pNR2B) pathway and downstream calcium-calmodulin-dependent kinase II (CaMKII)/c-AMP-responsive element binding protein (pCREB) signaling were assessed.

Results

We observed dysfunction of inhibitory interneurons, and found that activation of GABABR ameliorated CM-induced hyperalgesia, repressed the CM-evoked elevation of synapse-associated protein levels and enhancement of synaptic transmission, alleviated the CM-triggered increases in the levels of central sensitization-related proteins, and inhibited CaMKII/pCREB signaling via the PKA/Fyn/pNR2B pathway. The inhibition of PKA suppressed the CM-induced activation of Fyn/pNR2B signaling.

Conclusion

These data reveal that the dysfunction of inhibitory interneurons contributes to central sensitization by regulating synaptic plasticity through the GABABR/PKA/Fyn/pNR2B pathway in the periaqueductal gray (PAG) of CM rats. Blockade of GABABR-pNR2B signaling might have a positive influence on the effects of CM therapy by modulating synaptic plasticity in central sensitization.
Eyes on the road: brain computer interfaces and cognitive distraction in traffic
Authors: Bosch Victoria , Mecacci Giulio
Published: May 2023

Novel wearable neurotechnology is able to provide insight into its wearer's cognitive processes and offers ways to change or enhance their capacities. Moreover, it offers the promise of hands-free device control. These brain-computer interfaces are likely to become an everyday technology in the near future, due to their increasing accessibility and affordability. We, therefore, must anticipate their impact, not only on society and individuals broadly but also more specifically on sectors such as traffic and transport. In an economy where attention is increasingly becoming a scarce good, these innovations may present both opportunities and challenges for daily activities that require focus, such as driving and cycling. Here, we argue that their development carries a dual risk. Firstly, BCI-based devices may match or further increase the intensity of cognitive human-technology interaction over the current hands-free communication devices which, despite being widely accepted, are well-known for introducing a significant amount of cognitive load and distraction. Secondly, BCI-based devices will be typically harder than hands-free devices to both visually detect (e.g., how can law enforcement check when these extremely small and well-integrated devices are used?) and restrain in their use (e.g., how do we prevent users from using such neurotechnologies without breaching personal integrity and privacy?). Their use in traffic should be anticipated by researchers, engineers, and policymakers, in order to ensure the safety of all road users.
Maternal preconception BMI and gestational weight gain are associated with weight retention and maternal and child body fat at 6–7 years postpartum in the PRECONCEPT cohort
Authors: Young Melissa F. , Nguyen Phuong Hong , Tran Lan Mai , Khuong Long Quynh , Hendrix Sara , Martorell Reynaldo , Ramakrishnan Usha
Published: May 2023

Background

There is limited evidence from prospective cohorts in low-resource settings on the long-term impact of pre-pregnancy body mass index (PPBMI) and gestational weight gain (GWG) on postpartum weight retention (PPWR) and maternal and child body composition.

Objectives

We examined the associations between PPBMI and timing of GWG on PPWR at 1, 2, and 6–7 years and maternal and child percent body fat at 6–7 years.

Methods

We used data from the PRECONCEPT study (NCT01665378) that included prospectively collected data on 864 mother–child pairs from preconception through 6–7 years postpartum. The key outcomes were PPWR at 1, 2, and 6–7 years, and maternal and child percent body fat at 6–7 years that was measured using bioelectric impedance. Maternal conditional GWG (CGWG) was defined as window-specific weight gains (< 20wk, 21-29wk, and  ≥ 30wk), uncorrelated with PPBMI and all prior body weights. PPBMI and CGWG were calculated as standardized z-scores to allow for relative comparisons of a 1 standard deviation (SD) increase in weight gain for each window. We used multivariable linear regressions to examine the associations, adjusting for baseline demographic characteristics, intervention, breastfeeding practices, diet and physical activity.

Results

Mean (SD) PPBMI and GWG were 19.7 (2.1) kg/m2 and 10.2 (4.0) kg, respectively. Average PPWR at 1, 2, and 6–7 years was 1.1, 1.5 and 4.3 kg, respectively. A one SD increase in PPBMI was associated with a decrease in PPWR at 1 year (β [95% CI]: −0.21 [−0.37, −0.04]) and 2 years (−0.20 [−0.39, −0.01]); while a one SD in total CGWG was associated with an increase in PPWR at 1 year (1.01 [0.85,1.18]), 2 years (0.95 [0.76, 1.15]) and 6–7 years (1.05 [0.76, 1.34]). Early CGWG (< 20 weeks) had the greatest association with PPWR at each time point as well as with maternal (0.67 [0.07, 0.87]) and child (0.42 [0.15, 0.69]) percent body fat at 6–7 years.

Conclusion

Maternal nutrition before and during pregnancy may have long-term implications for PPWR and body composition. Interventions should consider targeting women preconception and early in pregnancy to optimize maternal and child health outcomes.
Spinal cord vascular degeneration impairs duloxetine penetration
Authors: Da Vitoria Lobo M. E , Madden R , Liddell S , Hirashima M , Hulse R. P
Published: May 2023

Introduction

Chronic pain is a prevalent physically debilitating health-related morbidity. Frontline analgesics are inadequate, providing only partial pain relief in only a proportion of the patient cohort. Here, we explore whether alterations in spinal cord vascular perfusion are a factor in reducing the analgesic capability of the noradrenaline reuptake inhibitor, duloxetine.

Method

An established rodent model of spinal cord vascular degeneration was used. Endothelial-specific vascular endothelial growth factor receptor 2 knockout mouse was induced via hydroxytamoxifen administered via intrathecal injection. Duloxetine was administered via intraperitoneal injection, and nociceptive behavioural testing was performed in both WT and VEGFR2KO mice. LC-MS/MS was performed to explore the accumulation of duloxetine in the spinal cord in WT and VEGFR2KO mice.

Results

Spinal cord vascular degeneration leads to heat hypersensitivity and a decline in capillary perfusion. The integrity of noradrenergic projections (dopa - hydroxylase labelled) in the dorsal horn remained unaltered in WT and VEGFR2KO mice. There was an association between dorsal horn blood flow with the abundance of accumulated duloxetine in the spinal cord and analgesic capacity. In VEGFR2KO mice, the abundance of duloxetine in the lumbar spinal cord was reduced and was correlated with reduced anti-nociceptive capability of duloxetine.

Discussion

Here, we show that an impaired vascular network in the spinal cord impairs the anti-nociceptive action of duloxetine. This highlights that the spinal cord vascular network is crucial to maintaining the efficacy of analgesics to provide pain relief.
Development of a population pharmacokinetic model of pyrazinamide to guide personalized therapy: impacts of geriatric and diabetes mellitus on clearance
Authors: Kim Ryunha , Jayanti Rannissa Puspita , Lee Hongyeul , Kim Hyun-Kuk , Kang Jiyeon , Park I-Nae , Kim Jehun , Oh Jee Youn , Kim Hyung Woo , Lee Heayon , Ghim Jong-Lyul , Ahn Sangzin , Long Nguyen Phuoc , Cho Yong-Soon , Shin Jae-Gook , On behalf of the cPMTb
Published: May 2023

Objectives: This study was performed to develop a population pharmacokinetic model of pyrazinamide for Korean tuberculosis (TB) patients and to explore and identify the influence of demographic and clinical factors, especially geriatric diabetes mellitus (DM), on the pharmacokinetics (PK) of pyrazinamide (PZA).

Methods: PZA concentrations at random post-dose points, demographic characteristics, and clinical information were collected in a multicenter prospective TB cohort study from 18 hospitals in Korea. Data obtained from 610 TB patients were divided into training and test datasets at a 4:1 ratio. A population PK model was developed using a nonlinear mixed-effects method.

Results: A one-compartment model with allometric scaling for body size effect adequately described the PK of PZA. Geriatric patients with DM (age >70 years) were identified as a significant covariate, increasing the apparent clearance of PZA by 30% (geriatric patients with DM: 5.73 L/h; others: 4.50 L/h), thereby decreasing the area under the concentration–time curve from 0 to 24 h by a similar degree compared with other patients (geriatric patients with DM: 99.87 μg h/mL; others: 132.3 μg h/mL). Our model was externally evaluated using the test set and provided better predictive performance compared with the previously published model.

Conclusion: The established population PK model sufficiently described the PK of PZA in Korean TB patients. Our model will be useful in therapeutic drug monitoring to provide dose optimization of PZA, particularly for geriatric patients with DM and TB.