bluuebunny/crossref_metadata_2025 huggingface dataset:
Movement and survival of captive-bred Limosa harlequin frogs (Atelopus limosus) released into the wild
Authors: Klocke Blake , Estrada Angie , Mataya Mirjana , Medina Daniel , Baitchman Eric , Belden Lisa , Guerrel Jorge , Evans Matthew , Baughman Jeff , Connette Grant , Illueca Estefany , Ibáñez Roberto , Gratwicke Brian
Published: July 2023

The endangered Limosa harlequin frog Atelopus limosus has experienced significant chytridiomycosis-related declines, but has been successfully bred in captivity as part of the Panama Amphibian Rescue and Conservation Project. We conducted the first Atelopus release trial using 83 captive-bred A. limosus, and monitored individuals as they transitioned from captivity back into the wild at a site within their historic distribution with no extant population. We acclimated 23 animals to the environment prior to release by holding them in mesocosms for 30 days (soft release) and released a further 60 animals without prior acclimation (hard release). We radio-tracked a subsample of animals in each treatment group. We used a Bayesian mark–recapture analysis to integrate known fate data from radio-tracked individuals with data from resighted individuals that had unknown fates. For this analysis, we allowed survival to differ between release treatments (hard vs. soft) and assumed detection probability would differ between tracking methods. Per-survey detection probability was about 0.02 for individuals without radio transmitters vs. 0.88 for radio-tracked frogs. We observed that hard-released animals initially dispersed further than soft-released animals, and, despite the fact that 25% of the soft-released animals were Batrachochytrium dendrobatidis (Bd)-positive on release day, their estimated 30-day survival probability was 0.46 (vs. 0.31 for the hard-released animals). The insights from this release trial can be used in an adaptive management framework to improve and refine release methods that will inform the nascent field of amphibian reintroduction ecology.
A review on deep learning applications in highly multiplexed tissue imaging data analysis
Authors: Zidane Mohammed , Makky Ahmad , Bruhns Matthias , Rochwarger Alexander , Babaei Sepideh , Claassen Manfred , Schürch Christian M.
Published: July 2023

Since its introduction into the field of oncology, deep learning (DL) has impacted clinical discoveries and biomarker predictions. DL-driven discoveries and predictions in oncology are based on a variety of biological data such as genomics, proteomics, and imaging data. DL-based computational frameworks can predict genetic variant effects on gene expression, as well as protein structures based on amino acid sequences. Furthermore, DL algorithms can capture valuable mechanistic biological information from several spatial “omics” technologies, such as spatial transcriptomics and spatial proteomics. Here, we review the impact that the combination of artificial intelligence (AI) with spatial omics technologies has had on oncology, focusing on DL and its applications in biomedical image analysis, encompassing cell segmentation, cell phenotype identification, cancer prognostication, and therapy prediction. We highlight the advantages of using highly multiplexed images (spatial proteomics data) compared to single-stained, conventional histopathological (“simple”) images, as the former can provide deep mechanistic insights that cannot be obtained by the latter, even with the aid of explainable AI. Furthermore, we provide the reader with the advantages/disadvantages of DL-based pipelines used in preprocessing highly multiplexed images (cell segmentation, cell type annotation). Therefore, this review also guides the reader to choose the DL-based pipeline that best fits their data. In conclusion, DL continues to be established as an essential tool in discovering novel biological mechanisms when combined with technologies such as highly multiplexed tissue imaging data. In balance with conventional medical data, its role in clinical routine will become more important, supporting diagnosis and prognosis in oncology, enhancing clinical decision-making, and improving the quality of care for patients.
Krill oil treatment ameliorates lipid metabolism imbalance in chronic unpredicted mild stress-induced depression-like behavior in mice
Authors: Zhang Hao , Liu Xiaofang , Li Bo , Zhang Yi , Gao Hua , Zhao Xianyong , Leng Kailiang , Song Zhenhua
Published: July 2023

The pathology of depression involves various factors including the interaction between genes and the environment. The deficiency of n-3 polyunsaturated fatty acids (n-3 PUFAs) in the brain and depressive symptoms are closely related. Krill oil contains abundant amounts of n-3 PUFAs incorporated in phosphatidylcholine. However, the effect of krill oil treatment on depression-like behaviors induced by chronic stress and its molecular mechanism in the brain remain poorly understood. Here, we used a chronic unpredictable mild stress (CUMS) model to evaluate the effect of krill oil on depression-like behaviors and explored its molecular mechanism through lipid metabolomics and mRNA profiles in the whole brain. We observed that CUMS-induced depression-like behaviors were ameliorated by krill oil supplementation in mice. The metabolism of glycerophospholipids and sphingolipids was disrupted by CUMS treatment, which were ameliorated after krill oil supplementation. Further analysis found that differently expressed genes after krill oil supplementation were mainly enriched in the membrane structures and neuroactive ligand–receptor interaction pathway, which may be responsible for the amelioration of CUMS-induced depression-like behaviors. Altogether, our results uncovered the relationship between lipid metabolism and CUMS, and provided new strategies for the prevention and treatment of depression.
Spermatogonial fate in mice with increased activin A bioactivity and testicular somatic cell tumours
Authors: Whiley Penny A. F. , Nathaniel Benedict , Stanton Peter G. , Hobbs Robin M. , Loveland Kate L.
Published: July 2023

Adult male fertility depends on spermatogonial stem cells (SSCs) which undergo either self-renewal or differentiation in response to microenvironmental signals. Activin A acts on Sertoli and Leydig cells to regulate key aspects of testis development and function throughout life, including steroid production. Recognising that activin A levels are elevated in many pathophysiological conditions, this study investigates effects of this growth factor on the niche that determines spermatogonial fate. Although activin A can promote differentiation of isolated spermatogonia in vitro, its impacts on SSC and spermatogonial function in vivo are unknown. To assess this, we examined testes of Inha KO mice, which feature elevated activin A levels and bioactivity, and develop gonadal stromal cell tumours as adults. The GFRA1+ SSC-enriched population was more abundant and proliferative in Inha KO compared to wildtype controls, suggesting that chronic elevation of activin A promotes a niche which supports SSC self-renewal. Intriguingly, clusters of GFRA1+/EOMES+/LIN28A– cells, resembling a primitive SSC subset, were frequently observed in tubules adjacent to tumour regions. Transcriptional analyses of Inha KO tumours, tubules adjacent to tumours, and tubules distant from tumour regions revealed disrupted gene expression in each KO group increased in parallel with tumour proximity. Modest transcriptional changes were documented in Inha KO tubules with complete spermatogenesis. Importantly, tumours displaying upregulation of activin responsive genes were also enriched for factors that promote SSC self-renewal, including Gdnf, Igf1, and Fgf2, indicating the tumours generate a supportive microenvironment for SSCs. Tumour cells featured some characteristics of adult Sertoli cells but lacked consistent SOX9 expression and exhibited an enhanced steroidogenic phenotype, which could arise from maintenance or acquisition of a fetal cell identity or acquisition of another somatic phenotype. Tumour regions were also heavily infiltrated with endothelial, peritubular myoid and immune cells, which may contribute to adjacent SSC support. Our data show for the first time that chronically elevated activin A affects SSC fate in vivo. The discovery that testis stromal tumours in the Inha KO mouse create a microenvironment that supports SSC self-renewal but not differentiation offers a strategy for identifying pathways that improve spermatogonial propagation in vitro.
Chemical insights into the synthetic chemistry of five-membered saturated heterocycles—a transition metal–catalyzed approach
Authors: Sunbal  , Alamzeb Muhammad , Omer Muhammad , Abid Obaid-Ur-Rahman , Ullah Mohib , Sohail Muhammad , Ullah Ihsan
Published: July 2023

Drug design and delivery is primarily based on the hunt for new potent drug candidates and novel synthetic techniques. Recently, saturated heterocycles have gained enormous attention in medicinal chemistry as evidenced by the medicinal drugs listed in the FDA Orange Book. Therefore, the demand for novel saturated heterocyclic syntheses has increased tremendously. Transition metal (TM)–catalyzed reactions have remained the prime priority in heterocyclic syntheses for the last three decades. Nowadays, TM catalysis is well adorned by combining it with other techniques such as bio- and/or enzyme-catalyzed reactions, organocatalysis, or using two different metals in a single catalysis. This review highlights the recent developments of the transition metal–catalyzed synthesis of five-membered saturated heterocycles.
Blood pressure control and left ventricular echocardiographic progression in hypertensive patients: an 18-month follow-up study
Authors: Yang Yan , Li Yan , Zhu Limin , Xu Jianzhong , Tang Xiaofeng , Gao Pingjin
Published: July 2023

Objectives

The impact of blood pressure (BP) control and its timing on left ventricular (LV) structure and function remains unclear. The present study was to evaluate whether BP control correlated with conventional LV geometry and function indexes or global longitudinal strain (GLS) progression, and when echocardiographic changes would occur in essential hypertension.

Methods and results

A total of 62 participants (mean age 55.2 ± 11.5, male 71.0%) with uncontrolled hypertension were enrolled in the longitudinal study. Patients were followed up at the 6-month and 18-month, when echocardiographic measurements were performed and BP control was evaluated during the follow up period. At the 6- and 18-month examination, we divided the hypertensive patients into two groups as BP controlled and uncontrolled group. Patients with BP uncontrolled (n = 33) had higher LV mass index (P = 0.02), higher left atrial volume index (P = 0.01), worse GLS (P = 0.005) and GLS changes (P = 0.003) compared with controlled BP (n = 29) at the 6-month follow-up examination. Patients with uncontrolled BP (n = 25) had higher LV mass index (P = 0.001), higher LV mass index changes (P = 0.01), higher relative wall thickness (P = 0.01), higher E/e′ (P = 0.046), worse GLS (P = 0.02) and GLS changes (P = 0.02) compared to BP controlled group (n = 24) at the 18-month follow-up examination. GLS changes were associated with BP control (β = 0.370, P = 0.004 at the 6-month examination and β = 0.324, P = 0.02 at the 18-month examination, respectively) in stepwise multivariate regression analysis. LV mass index changes was corelated with systolic BP (β = 0.426, P = 0.003) at the 18-month follow-up examination in stepwise multivariate regression analysis. Neither was GLS changes nor LV mass index changes were related to antihypertensive medication class, including combination therapy in 6- or 18-month follow up examination.

Conclusions

Our findings offer new clinical evidence on the association of BP control with echocardiographic changes in hypertensive patients, and, in particular, support the view that GLS progression was earlier and subtler than conventional LV geometry and function parameters. GLS changes were significant between BP controlled and uncontrolled patients even in 6-month follow-up period.
The causal effects of genetically determined human blood metabolites on the risk of atrial fibrillation
Authors: Cheng Tao , Wang Huan , Hu Yuanhui
Published: July 2023

Background

Blood metabolites have been found related to atrial fibrillation (AF), but the causal role is still unclear. Mendel randomization (MR) can give information about the causality between blood metabolites and AF.

Methods

Two-sample MR analysis was used to evaluate the causality between 486 blood metabolites and AF. Firstly, the genome-wide association study (GWAS) data for AF (from Nielsen et al.) was analyzed and some metabolites were identified. Then another GWAS data for AF (from Roselli et al.) was repeatedly analyzed to verify the results. Inverse variance weighted method was mainly used to determine the causality, and MR-egger, Weighted Median, and MR-PRESSO models were used as supplements of MR. Cochran's Q test was used to assess heterogeneity. And MR-Egger intercept and MR-PRESSO global test were performed to measure pleiotropy.

Results

The study used Bonferroni's corrected P value (P < 1.03 × 10−4) as the significance threshold. After MR analysis and replication analysis, we found two overlapped metabolites. Among which tryptophan betaine was the most significant causal metabolite in both AF GWAS data (from Nielsen et al.) (odds ratio (OR) = 0.83, 95% confidence interval (CI) = 0.76–0.90, P = 9.37 × 10−6) and AF GWAS data (from Roselli et al.) (OR = 0.82, 95% CI = 0.76–0.88, P = 2.00 × 10−7), while uridine was nominally significant metabolites in both AF GWAS data (from Nielsen et al.) (OR = 0.58, 95% CI = 0.40–0.84, P = 0.004) and AF GWAS data (from Roselli et al.) (OR = 0.56, 95% CI = 0.35–0.88, P = 0.01). And the results of sensitivity analysis showed that none of them had obvious heterogeneity or pleiotropy.

Conclusion

The study identified several blood metabolites that were causally related to AF, which may provide new perspectives on the pathogenesis of AF.
Melatonin intervention to prevent delirium in the intensive care units: a systematic review and meta-analysis of randomized controlled trials
Authors: Duan Yushan , Yang Yuan , Zhu Weihua , Wan Linjun , Wang Gang , Yue Jinxi , Bao Qi , Shao Jianlin , Wan Xiaohong
Published: July 2023

Objective

To determine the preventive effect of melatonin on delirium in the intensive care units.

Methods

We conducted a systematic search of the PubMed, Cochrane Library, Science, Embase, and CNKI databases, with retrieval dates ranging from the databases’ inception to September 2022. Controlled trials on melatonin and placebo for preventing delirium in the intensive care units were included. The meta-analysis was performed using Review Manager software (version 5.3) and Stata software (version 14.0).

Results

Six studies involving 2374 patients were included in the meta-analysis. The results of the meta-analysis showed that melatonin did not reduce the incidence of delirium in ICU patients (odds ratio [OR]: 0.71; 95% confidence interval [CI]: 0.46 to 1.12; p = 0.14). There was a strong hetero-geneity between the selected studies (I2 = 74%). Subgroup analysis results showed that melatonin reduced the incidence of delirium in cardiovascular care unit (CCU) patients (OR: 0.52; 95% CI: 0.37 to 0.73; p=0.0001), but did not in general intensive care unit (GICU) patients (OR: 1.14; 95% CI: 0.86 to 1.50; p=0.35). In terms of the secondary outcomes, there were no significant differences in all-cause mortality (OR: 0.85; 95% CI: 0.66 to 1.09; p=0.20), length of ICU stay (mean difference [MD]: 0.33; 95% CI: -0.53 to 1.18; p=0.45), or length of hospital stay (MD: 0.51; 95% CI: -1.17 to 2.19; p=0.55).

Conclusion

Melatonin reduced the incidence of delirium in CCU patients, but did not significantly reduce the incidence of delirium in GICU patients.

Systematic Review Registration

https://www.crd.york.ac.uk/prospero/, identifier CRD42022367665.
Uncovering the alarming rise of diabetic ketoacidosis during COVID-19 pandemic: a pioneer African study and review of literature
Authors: Gorchane Asma , Ach Taieb , Sahli Jihene , Abdelkrim Asma Ben , Mallouli Manel , Bellazreg Foued , Hachfi Wissem , Chaieb Molka Chadli , Ach Koussay
Published: July 2023

Introduction

Reports around the world indicate that COVID-19 pandemic may be contributing to an increase in the incidence of new onset diabetic ketoacidosis (DKA). This has yet to be studied in Africa. We aimed to compare the incidence trend of new onset DKA before and during the COVID-19 pandemic, with a focus on the type of diabetes mellitus (DM).

Materials and methods

This was a cross sectional analytical study, over a 4-year period, between March 2018 until February 2022 conducted in the referral center: diabetology department of university hospital Farhat Hached Sousse, Tunisia. The study population included patients hospitalized for new onset DKA divided in two groups: G1: before COVID-19 pandemic and G2: during COVID-19 pandemic. Patients younger than 14, new onset DM not presenting with DKA, other types of diabetes (monogenic, secondary or pancreatic diabetes) were not included. A statistical analysis of the monthly incidence trend was conducted using the Jointpoint software providing the average monthly percentage of change (AMPC).

Results

a total of 340 patients were included:137 registered before the pandemic and 203 during the pandemic, representing a 48.17% increase. The mean monthly incidence of new onset DKA during COVID-19 pandemic was statistically higher than that before COVID-19 pandemic (8.42 ± 4.87 vs 5.75 ± 4.29 DKA per month) (p=0.049). The temporal trend of DKA during the 4-year study showed a significant upward trend with a change in AMPC of +0.2% (p=0.037). The incidence of type 1 diabetes (T1D) and type 2 diabetes (T2D) increased by 50% and 44% respectively during COVID-19 pandemic. Anti-glutamic acid decarboxylase (anti-GAD) antibodies’ titers significantly increased in G2 compared with G1 (median of 330[Q1–Q3]=[58.5–1795]vs 92.5[Q1–Q3]=[22.5–1074] respectively)(p=0.021).

Discussion

The incidence trend of DKA showed an increase during the COVID-19 pandemic along with an increase of T1D and T2D implying that the pandemic may have been the underlying factor of this upward trend.
The impact of government intervention on innovation efficiency of green technology—a threshold effect analysis based on environmental taxation and government subsidies
Authors: Li Liqin , Rao Minye
Published: July 2023

Research and promotion of green technology can improve energy efficiency and help to optimize energy structure, which are key considerations in achieving the “dual carbon” goals of carbon peaking and carbon neutrality. Owing to the “dual externality” arising from green technology innovation (GTI), government policies have an important impact on this area. Environmental taxes and government subsidies are important means for governments to improve GTI and optimize energy utilization, with different environmental taxes and subsidies having different impacts. This study evaluates the impact of environmental taxes and government subsidies in China from 2009 to 2019, and assesses how these policies interacted with each other to determine China’s efficiency in GTI over this period. The study’s findings based on analysis of 30 provinces and cities in China indicate that environmental taxes have a threshold effect on the development of green technologies, and that the current level of taxation is insufficient to encourage optimized development in this area. Government subsidies can also help to reduce the negative effects arising from the current environmental tax burden. To optimize government policy implementation in this area, improve the level of GTI, and improve energy use efficiency, this study proposes countermeasures based on differentiated policies, including gradually increasing the rate and scope of environmental taxation, and strengthening the supervision of government subsidies.
CNN-GRU model based on attention mechanism for large-scale energy storage optimization in smart grid
Authors: Li Xuhan
Published: July 2023

Introduction: Smart grid (SG) technologies have a wide range of applications to improve the reliability, economics, and sustainability of power systems. Optimizing large-scale energy storage technologies for smart grids is an important topic in smart grid optimization. By predicting the historical load and electricity price of the power system, a reasonable optimization scheme can be proposed.

Methods: Based on this, this paper proposes a prediction model combining a convolutional neural network (CNN) and gated recurrent unit (GRU) based on an attention mechanism to explore the optimization scheme of large-scale energy storage in a smart grid. The CNN model can extract spatial features, and the GRU model can effectively solve the gradient explosion problem in long-term forecasting. Its structure is simpler and faster than LSTM models with similar prediction accuracy. After the CNN-GRU extracts the data, the features are finally weighted by the attention module to improve the prediction performance of the model further. Then, we also compared different forecasting models.

Results and Discussion: The results show that our model has better predictive performance and computational power, making an important contribution to developing large-scale energy storage optimization schemes for smart grids.
Effects of digital economy and city size on green total factor productivity
Authors: Liu Zejie , Liu Jiandong , Yin Yuanyuan , Zhu Xianwen
Published: July 2023

Utilizing the digital economy’s contribution to green total factor productivity is a key strategy for accelerating China’s green growth, although more research is still needed to understand the mechanism of this influence. This study uses panel data from 282 Chinese prefecture-level cities from 2011 to 2019 to empirically assess the impact of the digital economy and city size on GTFP. First, GTFP overall exhibits an upward trend with excellent spatial correlation and minimal regional variation. Second, the findings demonstrate that, while surrounding locations’ GTFP is not affected by the digital economy, local productivity can be improved. Third, the heterogeneity study demonstrates that the digital economy contributes more to local GTFP in the eastern region compared to the central and western regions, with the central region making the largest contribution to GTFP in the surrounding regions; the first, second, and third tier cities have more contributions from the digital economy to local and neighboring GTFP than the fourth and fifth tier cities. Fourth, city size positively modifies the relationship between the green total factor productivity and the digital economy. The western region is where the positive moderating effect of city size expansion is greatest. Moreover, compared to first-, second-, and third-tier cities, the fourth- and fifth-tier cities have a stronger beneficial moderating effect of city size increase. In light of this, we should focus on the growth of the digital economy, optimize city scale, and fully exploit the scale effect produced by the concentration of the digital industries and the spillover effect produced by the spread of the digital technology.
New landscape-perspective exploration of Moso bamboo forests under on/off-year phenomena and human activities
Authors: Li Longwei , Zhu Huizi , Wu Tianzhen , Wei Linjia , Li Nan
Published: July 2023

On-year and off-year phenomena is an unique spatiotemporal characteristics of Moso bamboo forests (MBFs), the combination of multiple sources data to assess the impact of on-/off-year phenomena and human activities is a new perspective to better understand MBFs. There is an urgent need to explore how to characterize the spatial variability of MBFs, whether there is a pattern in the spatial distribution of MBFs boundary lines, and whether the causes of the boundary lines are directly related to human activities. In this paper, Anji County, with a large MBF area, was selected as the study area. Based on Sentinel-2 time-series data, topography and impermeability data, the on-year/off-year status and boundary lines of MBFs were determined, and the Integrated Moso bamboo On-off year Differentiation Index (IMODI) was proposed to evaluate spatial differentiation. Spatial heterogeneity, the shape pattern of boundary lines, and the impact of human activities on the MBFs were quantitatively analyzed, and 631.5 km2 of MBFs and 140 on-off boundaries were accurately obtained. The on-year and off-year MBFs and boundaries were mainly distributed in mountainous areas, especially at elevations of 100–400 m and on slopes of 10–35°. The patterns in elevation can be categorized as stable, single-change, ascending-descending and descending-ascending patterns. The patterns in slope can be summarized as stable, single-change, and trapezoidal patterns. The newly proposed IMODI shows the best performance in reflecting the spatial differentiation of MBFs, and the on-year and off-year phenomenon of MBFs was closely related to human activities because the boundary lines were mostly concentrated within 2 km of villages. The results of this paper provide a new perspective to understand landscape of MBFs and the integrated management of carbon sequestration and sinks.
Comparative analysis of full-length 16s ribosomal RNA genome sequencing in human fecal samples using primer sets with different degrees of degeneracy
Authors: Waechter Christian , Fehse Leon , Welzel Marius , Heider Dominik , Babalija Lek , Cheko Juan , Mueller Julian , Pöling Jochen , Braun Thomas , Pankuweit Sabine , Weihe Eberhard , Kinscherf Ralf , Schieffer Bernhard , Luesebrink Ulrich , Soufi Muhidien , Ruppert Volker
Published: July 2023

Next-generation sequencing has revolutionized the field of microbiology research and greatly expanded our knowledge of complex bacterial communities. Nanopore sequencing provides distinct advantages, combining cost-effectiveness, ease of use, high throughput, and high taxonomic resolution through its ability to process long amplicons, such as the entire 16s rRNA genome. We examine the performance of the conventional 27F primer (27F-I) included in the 16S Barcoding Kit distributed by Oxford Nanopore Technologies (ONT) and that of a more degenerate 27F primer (27F-II) in the context of highly complex bacterial communities in 73 human fecal samples. The results show striking differences in both taxonomic diversity and relative abundance of a substantial number of taxa between the two primer sets. Primer 27F-I reveals a significantly lower biodiversity and, for example, at the taxonomic level of the phyla, a dominance of Firmicutes and Proteobacteria as determined by relative abundances, as well as an unusually high ratio of Firmicutes/Bacteriodetes when compared to the more degenerate primer set (27F-II). Considering the findings in the context of the gut microbiomes common in Western industrial societies, as reported in the American Gut Project, the more degenerate primer set (27F-II) reflects the composition and diversity of the fecal microbiome significantly better than the 27F-I primer. This study provides a fundamentally relevant comparative analysis of the in situ performance of two primer sets designed for sequencing of the entire 16s rRNA genome and suggests that the more degenerate primer set (27F-II) should be preferred for nanopore sequencing-based analyses of the human fecal microbiome.
The last flight of F/O Tadeusz Stabrowski. Identification of the polish pilot
Authors: Lisman Dagmara , Drath Joanna , Teul Iwona , Zielińska Grażyna , Szargut Maria , Dowejko Joanna , Cytacka Sandra , Piątek Jarosław , Ambroziak Jan , Śliżewski Grzegorz , Ossowski Andrzej
Published: July 2023

The paper presents the process of identifying an unnamed soldier of the Polish armed forces in the west, whose remains were found in a nameless grave at the municipal cemetery in Le Crotoy in France. The Polish Genetic Database of Victims of Totalitarianism team carried out the research in cooperation with the Ministry of Culture and National Heritage. A comprehensive analysis of autosomal and Y-STR markers was performed. Historical, anthropological, and forensic examinations of the remains were also carried out. The items found with the remains were also examined. Identification based on DNA analysis made it possible to restore the identity of the Polish pilot who died on 11 March 1943 near the French coast, F/O Tadeusz Stabrowski. The airman regained his name in 2018, he was about 26 years old at the time of his death and left behind a grieving wife and son in the United Kingdom. The success of identifying the NN remains was guaranteed by the appointment of an interdisciplinary team consisting of specialists in archaeology, anthropology, history, forensic medicine and forensic genetics. The analysis of historical sources allowed to determine 4 missing airmen whose remains could have been buried in the cemetery in Le Crotoy. An interesting aspect of the research was the cooperation with history enthusiasts and fans of Polish aviation, thanks to which it was finally possible to narrow down the group of pilots sought and reach the family of Tadeusz Stabrowski, who submitted comparative material for research. This is the first case of establishing the identity of a Polish pilot killed in France. Many institutions have been involved in the project, including Polish Ministry of Culture and National Heritage (MDiKN), which partially funded the research.
IL-15 armoring enhances the antitumor efficacy of claudin 18.2-targeting CAR-T cells in syngeneic mouse tumor models
Authors: Shi Hongtai , Li Andi , Dai Zhenyu , Xue Jiao , Zhao Qi , Tian Jiyuan , Song Dandan , Wang Hao , Chen Jianan , Zhang Xiaokang , Zhou Kaisong , Wei Huafeng , Qin Songbing
Published: July 2023

Claudin 18.2 (CLDN18.2)-targeting chimeric antigen receptor (CAR)-modified T cells are one of the few cell therapies currently producing an impressive therapeutic effect in treating solid tumors; however, their long-term therapeutic efficacy is not satisfactory with a short duration of response. Transgenic expression of interleukin (IL)-15 has been reported to promote T-cell expansion, survival, and function and enhance the antitumor activity of engineered T cells in vitro and in vivo. Therefore, this study aimed to explore whether IL-15 modification would increase the antitumor activity of CLDN18.2-targeting CAR-modified T (CAR-T) cells in immunocompetent murine tumor models. CLDN18.2-specific CAR-T cells with (H9 CAR-IL15) or without transgenic IL-15 expression (H9 CAR) were generated by retroviral transduction of mouse splenic T cells. In vitro, compared with H9 CAR T cells, H9 CAR-IL15 T cells exhibited better expansion and viability in the absence of antigen stimulation, with a less differentiated and T-cell exhausted phenotype; although IL-15 modification did not affect the production of effector cytokines and cytotoxic activity in the short-term killing assay, it moderately improved the in vitro recursive killing activity of CAR-T cells against CLDN18.2-expressing tumor cells. In vivo, H9 CAR T cells showed no antitumor activity against CLDN18.2-expressing pancreatic tumors in immunocompetent mice without lymphodepleting pretreatment; however, H9 CAR-IL15 T cells produced significant tumor-suppressive effects. Furthermore, H9 CAR-IL15 T cells exhibited greater in vivo expansion and tumor infiltration when combined with lymphodepleting preconditioning, resulting in superior antitumor activity in two murine tumor models and a survival advantage in one tumor model. We further demonstrated that recurrent tumors following H9 CAR-IL15 T-cell therapy downregulated CLDN18.2 expression, suggesting immune escape through the selection of antigen-negative cells under persistent CAR-T-cell immune pressure. In conclusion, our findings provide preclinical evidence supporting the clinical evaluation of IL-15-expressing CLDN18.2 CAR-T cells in patients with CLDN18.2-positive tumors.
High expression of IL6 and decrease in immune cells in COVID-19 patients combined with myocardial injury
Authors: Chen Tingting , Chen Haixin , Chen Ping , Zhu Linchao , Mao Wei , Yao Yimin
Published: July 2023

Purpose

Myocardial injury, as a serious complication of coronavirus disease-2019 (COVID-19), increases the occurrence of adverse outcomes. Identification of key regulatory molecules of myocardial injury may help formulate corresponding treatment strategies and improve the prognosis of COVID-19 patients.

Methods

Gene Set Enrichment Analysis (GSEA) was conducted to identify co-regulatory pathways. Differentially expressed genes (DEGs) in GSE150392 and GSE169241 were screened and an intersection analysis with key genes of the co-regulatory pathway was conducted. A protein-protein interaction (PPI) network was constructed to screen for key regulatory genes. Preliminarily screened genes were verified using other datasets to identify genes with consistent expression. Based on the hierarchical cluster, we divided the patients from GSE177477 into high- and low-risk groups and compared the proportion of immune cells. A total of 267 COVID-19 patients from the Zhejiang Provincial Hospital of Chinese Medicine from December 26, 2022, to January 11, 2023, were enrolled to verify the bioinformatics results. Univariate and multivariate analyses were performed to analyze the risk factors for myocardial injury. According to high-sensitivity troponin (hsTnI) levels, patients with COVID-19 were divided into high- and low-sensitivity groups, and interleukin 6 (IL6) expression and lymphocyte subsets were compared. Patients were also divided into high and low groups according to the IL6 expression, and hsTnI levels were compared.

Results

Interleukin signaling pathway and GPCR ligand binding were shown to be co-regulatory pathways in myocardial injury associated with COVID-19. According to the hierarchical cluster analysis of seven genes (IL6, NFKBIA, CSF1, CXCL1, IL1R1, SOCS3, and CASP1), patients with myocardial injury could be distinguished from those without myocardial injury. Age, IL6 levels, and hospital stay may be factors influencing myocardial injury caused by COVID-19. Compared with COVID-19 patients without myocardial injury, the levels of IL6 in patients with myocardial injury increased, while the number of CD4+ T cells, CD8+ T cells, B cells, and NK cells decreased (P<0.05). The hsTnI levels in COVID-19 patients with high IL6 levels were higher than those in patients with low IL6 (P<0.05).

Conclusions

The COVID-19 patients with myocardial injury had elevated IL6 expression and decreased lymphocyte counts. IL6 may participate in myocardial injury through the interleukin signaling pathway.
The impact of SARS-CoV-2 infection and vaccination on inflammatory arthritis: a cohort study
Authors: Striani Giovanni , Hoxha Ariela , Lorenzin Mariagrazia , Cozzi Giacomo , Scagnellato Laura , Vangelista Tatiana , Frizzera Francesca , De Sandre Pierino , Simioni Paolo , Doria Andrea , Ramonda Roberta
Published: July 2023

Objectives

To investigate the effects of SARS-CoV-2 infection, as well as short- (within 48 hours) and long-term (within 30 days) adverse events (AEs) of SARS-CoV-2 vaccines, including arthritis flares in a large cohort of patients with inflammatory arthritis (IA).

Methods

A retrospective cohort study comprising 362 patients: 94 (26%) rheumatoid arthritis, 158 (43.6%) psoriatic arthritis and 110 (30.4%) ankylosing spondylitis; and 165 healthy controls (HC) to ascertain the prevalence and severity of SARS-CoV-2 infection in patients with IA, the rate of AEs associated with SARS-CoV-2 vaccines and disease flares within a month of the vaccination. All patients provided informed consent and data about SARS-CoV-2 infection and/or vaccination status.

Results

One-hundred-seventeen (32.3%) patients and 39 (23.6%) HC were affected by SARS-CoV-2 infection. Forty (34.2%) patients experienced an IA flare within one month of infection, of whom 3 (7.5%) needed to switch therapy. The prevalence of SARS-CoV-2 infection, disease severity, and hospitalization rate were not significantly different. At least one shot of SARS-CoV-2 vaccine was administered in 331 (91.4%) patients and 147 (89.1%) HC. Within 48 hours, 102 (30.8%) patients developed vaccine-related AEs; 52 (15.7%) patients with >1 vaccine dose experienced an IA flare-up, of whom 12 (23.1%) needed to switch therapy.

Conclusions

A significantly higher rate of IA flare was observed among patients who contracted SARS-CoV-2 infection vs. those without infection. Patients with IA experienced flares after SARS-CoV-2 vaccination, though it was not statistically significant.
Retrospective on molecular assay design for detecting pan-orthopox viruses and prospective on mpox laboratory preparedness and readiness
Authors: Yeh Kenneth B. , Powers Michael D. , Patel Ami , Parekh Falgunee , Tseng Ashley S. , Bradford Elaine , Parker Kyle , Soong Ricky , Olinger Gene , Mombo Illich
Published: July 2023

The landscape of in vitro diagnostic (IVD) devices encompasses a broad range of tests that have been used to detect and diagnose pathogens, especially tropical diseases, for decades. The COVID-19 pandemic exemplified the greater need for bringing IVDs from the laboratory directly to the consumer, and recent outbreaks such as mpox, Sudan ebolavirus, and Marburg virus further reinforce this need. The increased emergence of tropical disease outbreaks requires more agile development, higher performance, and mass production of IVD devices. Furthermore, lessons learned in previous device developments can sometimes be used to accelerate new disease diagnostic applications. As an example, we describe one case history of an earlier pan-orthopox viral assay that detected smallpox variola and vaccinia strains, and also discerned related strains including mpox. This work established the foundation for the molecular detection of orthopox viruses, which could be mobilized to address public health needs once an emergency declaration was made that opened the FDA pathway for issuing an emergency use authorization for the use of these assays. Thus, the utilization of knowledge from earlier investments was shown to enhance preparedness and readiness. Here in this retrospective, we elaborate on the processes that enable this approach, including multi-disciplinary and multisectoral collaborations to accomplish a holistic, one health world.
Ultrasonographic study of female perineal body and its supportive function on pelvic floor
Authors: Zhou Minzhi , Shui Wen , Bai Wenkun , Wu Xing , Ying Tao
Published: July 2023

Objectives

The study aimed to observe, measure the size and elastic value of perineal body (PB) and assess its association with levator hiatus.

Methods

Datasets were acquired in 45 nulliparous, 66 POP women and 70 postpartum women using ultrasound. The PB was measured in depth, height, and Young’s modulus. The datasets were compared to assess whether there are some differences in the morphology, dimension and elastography modulus of PB among women. Pearson correlation analysis was used to evaluate the association between the morphology measurements (ΔValsalva-rest[v-r]), tissue mechanical properties (ΔValsalva-rest[v-r]) of the PB and levator hiatus area (ΔValsalva-rest[v-r]) to preliminarily explore whether PB can influence levator hiatus.

Results

Four representative manifestations of PB were presented in our study. Nulliparous women had smaller diameters and bigger Young’s modulus while postpartum women had bigger diameters and smaller Young’s modulus. POP and postpartum women had bigger levator hiatal distensibility and PB extensibility. There was no statistical association between PB measurements and levator hiatal area.

Conclusion

It is feasible to observe the morphology of PB and assess the dimension and elastography modulus by high-frequency ultrasound. The manifestations and measurements of PB are influenced by parity and long-term increased abdominal pressure. Our study preliminarily shows that PB has little effect on levator hiatus area.
Colonization of Serendipita indica promotes resistance against Spodoptera exigua in onion (Allium cepa L.)
Authors: Roylawar Praveen , Khandagale Kiran , Nanda Satyabrata , Soumia Parakkattu Sulochanan , Jadhav Sangita , Mahajan Vijay , Gawande Suresh
Published: July 2023

Plant-endophyte symbiosis influences plant defense and growth. Serendipita indica is a root endophyte that promotes growth and induces tolerance against biotic and abiotic stress in plants. In this study, we examined the effect of S. indica colonization on herbivore (Spodoptera exigua) resistance of onion (Allium cepa L.). We found that colonization of S. indica in the roots of onion significantly reduced the feeding damage of leaves by S. exigua larvae, and also resulted in a reduction in weight gain of the larvae when fed on S. indica plants. This enhanced resistance is a result of modulation of antioxidant and defense enzymes/genes in the host by S. indica mutualism. Specifically, the activities of enzymes such as Superoxide dismutase, peroxidase, polyphenol oxidase, phenylalanine ammonia-lyase, and H2O2 content were significantly higher in the early stages of S. exigua feeding in the S. indica colonized plants compared to the non-colonized counterparts. Similarly, defense genes also showed modulation in response to this tripartite interaction of onion -S. indica mutualism and S. exigua herbivory. The hierarchical cluster analysis and principal component analysis indicated a clear difference in the onion biochemical responses, which is due to the S. indica symbiosis. Our investigation demonstrates that onion-S. indica symbiosis significantly decreases chewing injury by efficiently modulating antioxidant and defense enzyme activities and gene expression in response to S. exigua herbivory. Therefore, S. indica can be used as a potential biocontrol agent for sustainable management of this important pest of Alliums.
Long-term quality of life after decompressive craniectomy
Authors: Buffagni Daniel , Zamarron Alvaro , Melgosa Isabel , Gutierrez-Gonzalez Raquel
Published: July 2023

Introduction

This study aims to assess the quality of life (QoL) in patients who have undergone decompressive craniectomy (DC) for any pathology that has caused life-threatening intracranial hypertension. Similarly, it aims to evaluate QoL perceived by caregivers or external informants. In addition to that, the last purpose is to determine which clinical or therapeutic factors could correlate with a better QoL.

Methods

A single-center cross-sectional study was designed. All patients over 18 years old who underwent a supratentorial DC at our department due to intracranial hypertension of any etiology, from January 2015 to December 2021, were retrospectively selected. Patients with incomplete follow-up (under 1 year from the event or those who died) or who declined to participate in the study were excluded. QoL was assessed with SF-36 and CAVIDACE scales. The correlation between clinical and therapeutic variables and SF-36 subscales was studied with Spearman's correlation and the Mann–Whitney U-test.

Results

A total of 55 consecutive patients were recruited: 22 patients had died, three were missed for follow-up, and 15 declined to participate, thus 15 subjects were finally included. The mean follow-up was 47 months (IQR 21.5–67.5). A significant reduction in the “role physical” and “role emotional” subscales of SF-36 was observed compared with the general population. According to caregivers, a significant reduction was assigned to the “physical wellbeing” and “rights” domains. The “physical functioning” score was poorer in women, older patients, those with dominant hemisphere disease, those who required tracheostomy, and those with poor outcomes in the modified Rankin scale. A strong correlation was found between the QoL index at the CAVIDACE scale and the SF-36 subscales “physical functioning” and “role physical”.

Conclusion

Most patients and caregivers reported acceptable QoL after DC due to a life-threatening disease. A significant reduction in SF- 36 subscales scores “role limitation due to physical problems” and “role limitation due to emotional problems” was referred by patients. According to caregivers' QoL perception, only 25% of the survey's participants showed low scores in the QoL index of the CAVIDACE scale. Only 26.7% of the patients showed mood disorders.
Efficacy and safety of hydrokinesitherapy in patients with dystrophinopathy
Authors: Suslov V. M. , Lieberman L. N. , Carlier P. G. , Ponomarenko G. N. , Ivanov D. O. , Rudenko D. I. , Suslova G. A. , Adulas E. I.
Published: July 2023

Duchenne muscular dystrophy (DMD) is one of the most common forms of hereditary muscular dystrophies in childhood and is characterized by steady progression and early disability. It is known that physical therapy can slow down the rate of progression of the disease. According to global recommendations, pool exercises, along with stretching, are preferable for children with DMD, as these types of activities have a balanced effect on skeletal muscles and allow simultaneous breathing exercises. The present study aimed to evaluate the effectiveness of regular pool exercises in patients with Duchenne muscular dystrophy who are capable of independent movement during 4 months of training. 28 patients with genetically confirmed Duchenne muscular dystrophy, who were aged 6.9 ± 0.2 years, were examined. A 6-min distance walking test and timed tests, namely, rising from the floor, 10-meter running, and stair climbing and descending, muscle strength of the upper and lower extremities were assessed on the baseline and during dynamic observation at 2 and 4 months. Hydrorehabilitation course lasted 4 months and was divided into two stages: preparatory and training (depend on individual functional heart reserve (IFHR)). Set of exercises included pool dynamic aerobic exercises. Quantitative muscle MRI of the pelvic girdle and thigh was performed six times: before training (further BT) and after training (further AT) during all course. According to the results of the study, a statistically significant improvement was identified in a 6-min walking test, with 462.7 ± 6.2 m on the baseline and 492.0 ± 6.4 m after 4 months (p < 0.001). The results from the timed functional tests were as follows: rising from the floor test, 4.5 ± 0.3 s on the baseline and 3.8 ± 0.2 s after 4 months (p < 0.001); 10 meter distance running test, 4.9 ± 0.1 s on the baseline and 4.3 ± 0.1 s after 4 months (p < 0.001); 4-stair climbing test, 3.7 ± 0.2 s on the baseline and 3.2 ± 0.2 s after 4 months (p < 0.001); and 4-stair descent test, 3.9 ± 0.1 s on the baseline and 3.2 ± 0.1 s after 4 months (p < 0.001). Skeletal muscle quantitative MRI was performed in the pelvis and the thighs in order to assess the impact of the procedures on the muscle structure. Muscle water T2, a biomarker of disease activity, did not show any change during the training period, suggesting the absence of deleterious effects and negative impact on disease activity. Thus, a set of dynamic aerobic exercises in water can be regarded as effective and safe for patients with DMD.