bluuebunny/crossref_metadata_2025 huggingface dataset:
The Issue of Women in Adjara in the Prism of Soviet Antireligious Policy (1920s)
Authors: Putkaradze Tamaz , Putkaradze Kakha
Published: May 2023

The purpose of the article to present the problem of women in the prism of the Soviet atheistic policy in Ajara in 1920s. Soviet religious policy from the very beginning was characterized by heterogeneity, bias, and one-sidedness, with communism and atheism considered as the mainstays of ideology. The Bolsheviks seemed to preach the inviolability of the religious feelings of the believers, but in fact fought with fire and sword against any manifestation of religiosity. The Soviet government encouraged controversy among believers. A clear confirmation of this was the so-called ‘The chador taking’ campaign, which has been met with serious controversy in the region. Examining the problems related to the wearing of the chador, presenting the issue of women in the context of anti-religious policies is the main task of our research.

The scientific novelty of the research is the discussion of the factors that collectively led to the 1929 mass protests in mountainous Adjara (Georgia). At the same time, a number of unpublished archival documents, which are kept in the Adjara State Archive, enter the scientific circulation. The factual materials presented in the article and the analysis of the documents kept in the Adjara Archives Division clearly show the Soviet policy of neglecting and insulting the religious feelings of believers, which led to the 1929 large-scale anti-Soviet protests in mountainous Adjara.

The methodological basis of the research is the universal scientific principles of objectivity, comprehensiveness and systematics, historical-comparative and historical-typological methods.

Conclusions. As a result of the research, the determining factors of the mass demonstrations of 1929 were identified, in particular: the anti-religious policy of the Soviet government, which included the implementation of various measures by the government, in particular: The formation of the League of Militant Atheists and other anti-religious bodies, the mass destruction of religious institutions, theatrics against religion, the introduction of various awards to reward activists who fight against religion, the creation of women’s committees and ‘Muslim women’s sections’ to separate women from the religion. Added to this was the rudeness and arbitrariness of the party officials in all spheres of public and social life, the imposition of various restrictions on religious services and other factors, the combination of which led to the mass uprising of 1929. The results of the research proved once again that despite the various methods used to intimidate the believers, the government was powerless to suppress the religious feelings of the people.
Non-Governmental Institutions as Actors of German ‘Soft Power’ in Ukraine (1992-2022)
Authors: Mateleshko Yurii
Published: May 2023

The purpose of the research paper is to characterize the activity of German non-governmental institutions (organizations) in Ukraine during 1992-2022 through the prism of the concept of ‘soft power’ by J. Nye, as well as to clarify the forms, aims, priorities, and results of their activity.

The scientific novelty is in the concept of ‘soft power’ application in the study of the activities of German non-governmental organizations in Ukraine at the time of independence.

The methodology of the research, which is essentially interdisciplinary, is based on the combination of the political science concept of J. Nye and the historical approach. The ‘soft power’ of Germany is analyzed as a combination of four components: resources (values, language, culture, etc.), actors (subjects of influence who use the attractiveness of the resources to involve target groups of the population), tools (means of influence including public diplomacy and its varieties), results (positive image, implementation of political and cultural values, etc.).

Conclusions. Since the beginning of its independence, Ukraine has become the object of significant interest both on the part of the government agencies of the Federal Republic of Germany and its numerous non-governmental institutions that have been active in our country since 1992.

German non-governmental organizations can be conditionally divided into two groups: 1) political, which primarily include party foundations; 2) cultural, educational, and scientific, among which the Goethe-Institut, the German Academic Exchange Service (DAAD), the German Wave (Deutsche Welle) and the Alexander von Humboldt Foundation should be singled out.

When implementing the ‘soft power’ policy, these institutions rest on such resources as democracy and a developed civil society’s values, the German language and culture, and the federal system of education and science. The activities of German non-governmental organizations in Ukraine generally correspond to their general goals.

Among the main results of these institutions’ activities can be named the formation of a positive image of Germany in Ukraine, as well as the spread of European political values among target groups of the Ukrainian population (mainly young people). The result of the latter has become the formation of civil society in Ukraine and increasing European integration, which has been also facilitated by the activities of other democratic countries’ institutions. However, confirmation of the last statement requires separate research. It also seems promising to study the relationship between Germany’s ‘soft power’ (or another Western country) and the emigration of the Ukrainian population during the period of independence.
Venom biotechnology: casting light on nature’s deadliest weapons using synthetic biology
Authors: Lüddecke Tim , Paas Anne , Harris Richard J. , Talmann Lea , Kirchhoff Kim N. , Billion André , Hardes Kornelia , Steinbrink Antje , Gerlach Doreen , Fry Bryan G. , Vilcinskas Andreas
Published: May 2023

Venoms are complex chemical arsenals that have evolved independently many times in the animal kingdom. Venoms have attracted the interest of researchers because they are an important innovation that has contributed greatly to the evolutionary success of many animals, and their medical relevance offers significant potential for drug discovery. During the last decade, venom research has been revolutionized by the application of systems biology, giving rise to a novel field known as venomics. More recently, biotechnology has also made an increasing impact in this field. Its methods provide the means to disentangle and study venom systems across all levels of biological organization and, given their tremendous impact on the life sciences, these pivotal tools greatly facilitate the coherent understanding of venom system organization, development, biochemistry, and therapeutic activity. Even so, we lack a comprehensive overview of major advances achieved by applying biotechnology to venom systems. This review therefore considers the methods, insights, and potential future developments of biotechnological applications in the field of venom research. We follow the levels of biological organization and structure, starting with the methods used to study the genomic blueprint and genetic machinery of venoms, followed gene products and their functional phenotypes. We argue that biotechnology can answer some of the most urgent questions in venom research, particularly when multiple approaches are combined together, and with other venomics technologies.
Human dental pulp stem cells (hDPSCs) promote the lipofibroblast transition in the early stage of a fibro-inflammatory process
Authors: Pisciotta Alessandra , Di Tinco Rosanna , Bertani Giulia , Orlandi Giulia , Bertoni Laura , Pignatti Elisa , Orciani Monia , Sena Paola , Bertacchini Jessika , Salvarani Carlo , Carnevale Gianluca
Published: May 2023

Introduction: In autoimmune diseases, particularly in systemic sclerosis and chronic periaortitis, a strict correlation between chronic inflammation and fibrosis exists. Since the currently used drugs prove mostly effective in suppressing inflammation, a better comprehension of the molecular mechanisms exerted by cell types implicated in fibro-inflammation is needed to develop novel therapeutic strategies. Mesenchymal stromal/stem cells (MSCs) are being matter of deep investigation to unveil their role in the evolution of fibrogenetic process. Several findings pointed out the controversial implication of MSCs in these events, with reports lining at a beneficial effect exerted by external MSCs and others highlighting a direct contribution of resident MSCs in fibrosis progression. Human dental pulp stem cells (hDPSCs) have demonstrated to hold promise as potential therapeutic tools due to their immunomodulatory properties, which strongly support their contribution to tissue regeneration.

Methods: Our present study evaluated hDPSCs response to a fibro-inflammatory microenvironment, mimicked in vitro by a transwell co-culture system with human dermal fibroblasts, at early and late culture passages, in presence of TGF-β1, a master promoter of fibrogenesis.

Results and Discussion: We observed that hDPSCs, exposed to acute fibro-inflammatory stimuli, promote a myofibroblast-to-lipofibroblast transition, likely based on BMP2 dependent pathways. Conversely, when a chronic fibro-inflammatory microenvironment is generated, hDPSCs reduce their anti-fibrotic effect and acquire a pro-fibrotic phenotype. These data provide the basis for further investigations on the response of hDPSCs to varying fibro-inflammatory conditions.
Protective effect of ursodeoxycholic acid on COVID-19 in patients with chronic liver disease
Authors: Li Yanyan , Zhu Na , Cui Xinyu , Lin Yingying , Li Xin
Published: May 2023

Objective

Ursodeoxycholic acid (UDCA) may reduce susceptibility to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection by downregulating angiotensin-converting enzyme 2 (ACE2), based on recent experimental investigation. This study aimed to determine the potential protective effect of UDCA against SARS-CoV-2 infection in patients with chronic liver disease.

Methods

Patients with chronic liver disease receiving UDCA (taking UDCA ≥1 month) at Beijing Ditan Hospital between January 2022 and December 2022 were consecutively enrolled. These patients were matched in a 1:1 ratio to those with liver disease not receiving UDCA during the same period by using a propensity score matching analysis with nearest neighbor matching algorithm. We conducted a phone survey of coronavirus disease 2019 (COVID-19) infection during the early phase of the pandemic liberation (from 15 December 2022 to 15 January 2023). The risk of COVID-19 was compared in two matched cohorts of 225 UDCA users and 225 non-UDCA users based on patient self-report.

Results

In the adjusted analysis, the control group was superior to the UDCA group in COVID-19 vaccination rates and liver function indicators, including γ-glutamyl transpeptidase and alkaline phosphatase (p < 0.05). UDCA was associated with a lower incidence of SARS-CoV-2 infection (UDCA 85.3% vs. control 94.2%, p = 0.002), more mild cases (80.0% vs. 72.0%, p = 0.047), and shorter median time from infection to recovery (5 vs. 7 days, p < 0.001). Logistic regression analysis showed that UDCA was a significant protective factor against COVID-19 infection (OR: 0.32, 95%CI: 0.16–0.64, p = 0.001). Furthermore, diabetes mellitus (OR: 2.48, 95%CI: 1.11–5.54, p = 0.027) and moderate/severe infection (OR: 8.94, 95%CI: 1.07–74.61, p = 0.043) were more likely to prolong the time from infection to recovery.

Conclusion

UDCA therapy may be beneficial in reducing COVID-19 infection risk, alleviating symptoms, and shortening the recovery time in patients with chronic liver disease. However, it should be emphasized that the conclusions were based on patient self-report rather than classical COVID-19 detection by experimental investigations. Further large clinical and experimental studies are needed to validate these findings.
Screening of linear B-cell epitopes and its proinflammatory activities of Haemophilus parasuis outer membrane protein P2
Authors: Wu Jingbo , Nan Wenjin , Peng Guoliang , Hu Honghui , Xu Chongbo , Huang Jianqiang , Xiao Zhengzhong
Published: May 2023

Haemophilus parasuis is a commensal organism of the upper respiratory tract of pigs, but virulent strains can cause Glässer’s disease, resulting in significant economic losses to the swine industry. OmpP2 is an outer membrane protein of this organism that shows considerable heterogeneity between virulent and non-virulent strains, with classification into genotypes I and II. It also acts as a dominant antigen and is involved in the inflammatory response. In this study, 32 monoclonal antibodies (mAbs) against recombinant OmpP2 (rOmpP2) of different genotypes were tested for reactivity to a panel of OmpP2 peptides. Nine linear B cell epitopes were screened, including five common genotype epitopes (Pt1a, Pt7/Pt7a, Pt9a, Pt17, and Pt19/Pt19a) and two groups of genotype-specific epitopes (Pt5 and Pt5-II, Pt11/Pt11a, and Pt11a-II). In addition, we used positive sera from mice and pigs to screen for five linear B-cell epitopes (Pt4, Pt14, Pt15, Pt21, and Pt22). After porcine alveolar macrophages (PAMs) were stimulated with overlapping OmpP2 peptides, we found that the epitope peptides Pt1 and Pt9, and the loop peptide Pt20 which was adjacent epitopes could all significantly upregulated the mRNA expression levels of IL-1α, IL-1β, IL-6, IL-8, and TNF-α. Additionally, we identified epitope peptides Pt7, Pt11/Pt11a, Pt17, Pt19, and Pt21 and loop peptides Pt13 and Pt18 which adjacent epitopes could also upregulate the mRNA expression levels of most proinflammatory cytokines. This suggested that these peptides may be the virulence-related sites of the OmpP2 protein, with proinflammatory activity. Further study revealed differences in the mRNA expression levels of proinflammatory cytokines, including IL-1β and IL-6, between genotype-specific epitopes, which may be responsible for pathogenic differences between different genotype strains. Here, we profiled a linear B-cell epitope map of the OmpP2 protein and preliminarily analyzed the proinflammatory activities and effects of these epitopes on bacterial virulence, providing a reliable theoretical basis for establishing a method to distinguish strain pathogenicity and to screen candidate peptides for subunit vaccines.
Spatial response of urban land use change and ecosystem service value in the lower reaches of the Yangtze River: A case study of Tongling, China
Authors: Liu Fang , Qin Tianling , Liu Shanshan , Wang Hao , Nie Hanjiang
Published: May 2023

Exploring the impact of urban land use change (LUC) on ecosystem services is significant for ensuring urban ecological security and realizing regional economic development. This study used land use data from 1985, 2000, 2014, and 2020 of Tongling city and the CA–Markov model to predict the LUC in 2025 and 2030. The spatio-temporal distribution characteristics of LUC during 1985–2030 were analyzed using the land use dynamics model and Sankey diagram. The vegetation-corrected ecological services value (ESV) equivalent was used to quantify the impact of LUC on ESV. Estimating the profit/loss value and spatial autocorrelation revealed ESV’s spatial and temporal dynamics in Tongling city. The results show that: 1) The most obvious LUC in the study area during 1985–2030 is the conversion of cultivated land to built-up land, in which the proportion of cultivated land decreased by 9.6%, and built-up land increased by 12.2%. 2) During 1985–2030, the ESV in Tongling showed an increasing trend at the beginning and then decreased, reaching a maximum value of 274.74 billion yuan in 2000. Regarding individual ecosystem service functions, the hydrological regulation function significantly contributed to ESV changes. The area change in paddy fields and built-up land had the most significant impact on ESV. 3) The total addition of ESV in Tongling during 1985–2030 was 5.98 billion yuan; the total loss was 18.59 billion yuan, and the net loss was 12.6 billion yuan. The proportion of area with ESV gains relative to the whole city is getting smaller, and the proportion of area with ESV losses is growing. The spatial autocorrelation shows the presence of high aggregation in ESV profit and loss areas. Simulating future LUC in Tongling and exploring ESV’s response is beneficial to developing new landscape patterns and ecological protection. It also provides a scientific basis for the extensive promotion of sustainable urban development in the future.
Multi-omics analysis of Siglec family genes in cutaneous melanoma
Authors: Li Kezhu , Xu Nan , Guo Shu
Published: May 2023

Background

Melanoma is widely recognized as the most aggressive and fatal type of skin cancer; however, effective prognostic markers are lacking. The sialic acid-binding immunoglobulin-type lectin (Siglec) gene family plays an important role in the development of tumors and immune escape, but its prognostic role in melanoma remains unknown.

Results

Siglec genes have a high mutation frequency, with up to 8% in SIGLEC7. High expression levels of Siglecs in tumor bulk suggests a better prognosis. Siglecs also show a high degree of synergistic expression. Immunohistochemistry was used to analyze the expression of SIGLEC9 in tumor tissue microarray. The expression of SIGLEC9 in tumor tissue without metastasis was higher than that in tumor tissue with metastasis. We used unsupervised clustering to create a high expression of Siglec (HES) cluster and a low expression of Siglec (LES) cluster. The HES cluster correlated with high overall survival and increased expression levels of Siglec genes. The HES cluster also showed significant immune cell infiltration and activation of immune signaling pathways. We used least absolute shrinkage and selection operator (LASSO) regression analysis to reduce the dimensionality of Siglec cluster-related genes and constructed a prognostic model composed of SRGN and GBP4, which can risk-stratify patients in both the training and test datasets.

Conclusion

We conducted a multi-omics analysis of the Siglec family genes in melanoma and found that Siglecs play an important role in the occurrence and development of melanoma. Typing constructed using Siglecs can show risk stratification and derived prognostic models can predict a patient’s risk score. In summary, Siglec family genes are potential targets for melanoma treatment as well as prognostic markers that can direct individualized treatments and improve overall survival.
Fatty acid analysis reveals the trophic interactions among organisms in the Zhelin Bay Marine Ranch
Authors: Li Changlin , Lin Huijie , Guo Yu , Yu Gang , Ma Zhenhua , Pei Kun , Qin Chuanxin
Published: May 2023

The fatty acid composition in organisms can reflect the trophic level, feeding habits, and utilization of local resources. In the present study, the living resources of different functional areas (artificial reef area, shellfish area, macroalgae area) in the Zhelin Bay Marine Ranch were investigated, and fatty acid analysis was used to elucidate the trophic relations across the food web. The results showed that 22:6ω3 FA (docosahexaenoic acid, DHA), 20:5ω3 FA (eicosapentaenoic acid, EPA), 16:1ω7 FA, and 16:0 FA are fatty acid biomarkers that distinguish carnivorous, omnivorous, and herbivorous organisms. The ratios of DHA/EPA, polyunsaturated fatty acids/saturated fatty acids (PUFA/SFA), and sum of ω3 fatty acids/sum of ω6 fatty acids (Σω3/Σω6) can be used as an important basis to assess the trophic level and feeding habits of organisms. In the comparison of the food web structure of different functional areas, the DHA/EPA ratio of carnivorous organisms in the Artificial Reef area was higher than that in other functional areas due to the abundant living resources, indicating that the food web of the Artificial Reef area presents lower stability to cope with perturbations. Furthermore, MixSIAR was used to quantitatively estimate the diet composition of consumers in the Zhelin Bay Marine Ranch based on their fatty acids. The results of the present study are a valuable contribution to understanding the trophic relationships in the Zhelin Bay Marine Ranch and provide theoretical support for future planning and construction of marine ranches.
Case report: Short-term eculizumab use in atypical HUS associated with Lemierre's syndrome and post-infectious glomerulonephritis
Authors: Sadiq Sanober , Urisman Anatoly , Cil Onur
Published: May 2023

Atypical hemolytic uremic syndrome (aHUS) is a rare disease caused by genetic abnormalities, infections, autoimmune diseases, drugs, and malignancies. Anti-C5 monoclonal antibody eculizumab is the mainstay of treatment of aHUS caused by the genetic defects of the alternative complement pathway. However, the utility of eculizumab in non-genetic forms of aHUS and the timing of treatment discontinuation remain controversial. Here, we report successful short-term eculizumab use in two young adult patients with aHUS due to rare infectious and autoimmune etiologies: Lemierre's syndrome and post-infectious glomerulonephritis, respectively. Eculizumab was rapidly discontinued in both patients with no aHUS recurrence during long-term follow-up. Considering its favorable safety profile with appropriate meningococcal prophylaxis, eculizumab can be considered as a treatment option for non-genetic aHUS.
Spatial and temporal dynamics at an actively silicifying hydrothermal system
Authors: Rasmussen Kalen L. , Stamps Blake W. , Vanzin Gary F. , Ulrich Shannon M. , Spear John R.
Published: May 2023

Steep Cone Geyser is a unique geothermal feature in Yellowstone National Park (YNP), Wyoming, actively gushing silicon-rich fluids along outflow channels possessing living and actively silicifying microbial biomats. To assess the geomicrobial dynamics occurring temporally and spatially at Steep Cone, samples were collected at discrete locations along one of Steep Cone’s outflow channels for both microbial community composition and aqueous geochemistry analysis during field campaigns in 2010, 2018, 2019, and 2020. Geochemical analysis characterized Steep Cone as an oligotrophic, surface boiling, silicious, alkaline-chloride thermal feature with consistent dissolved inorganic carbon and total sulfur concentrations down the outflow channel ranging from 4.59 ± 0.11 to 4.26 ± 0.07 mM and 189.7 ± 7.2 to 204.7 ± 3.55 μM, respectively. Furthermore, geochemistry remained relatively stable temporally with consistently detectable analytes displaying a relative standard deviation <32%. A thermal gradient decrease of ~55°C was observed from the sampled hydrothermal source to the end of the sampled outflow transect (90.34°C ± 3.38 to 35.06°C ± 7.24). The thermal gradient led to temperature-driven divergence and stratification of the microbial community along the outflow channel. The hyperthermophile Thermocrinis dominates the hydrothermal source biofilm community, and the thermophiles Meiothermus and Leptococcus dominate along the outflow before finally giving way to more diverse and even microbial communities at the end of the transect. Beyond the hydrothermal source, phototrophic taxa such as Leptococcus, Chloroflexus, and Chloracidobacterium act as primary producers for the system, supporting heterotrophic growth of taxa such as Raineya, Tepidimonas, and Meiothermus. Community dynamics illustrate large changes yearly driven by abundance shifts of the dominant taxa in the system. Results indicate Steep Cone possesses dynamic outflow microbial communities despite stable geochemistry. These findings improve our understanding of thermal geomicrobiological dynamics and inform how we can interpret the silicified rock record.
The association between stress, emotional states, and tinnitus: a mini-review
Authors: Patil Jayaditya Devpal , Alrashid Manar Abdulkarim , Eltabbakh Ayah , Fredericks Salim
Published: May 2023

Extensive literature supporting the view of tinnitus induced stress in patients is available. However, limited evidence has been produced studying the opposite, that is, does stress cause tinnitus? The hypothalamus pituitary adrenal axis, one of the main neuroendocrine systems involved in stress response, is commonly disturbed in tinnitus patients. Patients with chronic tinnitus have been shown to develop abnormal responses to psycho-social stress, where the hypothalamus pituitary adrenal axis response is weaker and delayed, suggesting chronic stress contributes to the development of chronic tinnitus. The sympathetic branch of the autonomic nervous system also plays a major role in stress response and its chronic hyperactivity seems to be involved in developing tinnitus. Psycho-social stress has been shown to share the same probability of developing tinnitus as occupational noise and contributes to worsening tinnitus. Additionally, exposure to high stress levels and occupational noise doubles the likelihood of developing tinnitus. Interestingly, short-term stress has been shown to protect the cochlea in animals, but chronic stress exposure has negative consequences. Emotional stress also worsens pre-existing tinnitus and is identified as an important indicator of tinnitus severity. Although there is limited body of literature, stress does seem to play a vital role in the development of tinnitus. This review aims to highlight the association between stress, emotional states, and the development of tinnitus while also addressing the neural and hormonal pathways involved.
Unique genotype-phenotype correlations within LAMA2-related limb girdle muscular dystrophy in Chinese patients
Authors: Huang Xiuli , Tan Dandan , Zhang Zaiqiang , Ge Lin , Liu Jieyu , Ding Juan , Yang Haipo , Wei Cuijie , Chang Xingzhi , Yuan Yun , Yan Chuanzhu , Xiong Hui
Published: May 2023

Background

LAMA2-related limb girdle muscular dystrophy (LGMD R23) is rare. The detailed clinical phenotypes and genetic information associated with LGMD R23 are unknown.

Methods

We conducted a retrospective cross-sectional and longitudinal study on 19 LGMD R23 patients.

Results

Normal early motor development was observed in 84.2% patients. Mild orthopedic complications were observed in 42.1% patients. 36.8% patients had seizures, which is unusually frequent in LGMD. Epilepsy was eventually diagnosed in 26.3% patients. 46.7% patients presented with motor neuropathy. Genetic analysis identified 29 pathogenic variants, with missense and frameshift variants being the most common. The mutant sites were mainly distributed in the N-terminal and G-like domains of laminin. The missense variants are distributed near the N-terminus (exons 3–11), whereas frameshift variants are distributed in exons 12–65. Five patients were diagnosed with epilepsy and all of them harbor at least one missense variants in exon 4. 71.4% variants of patients with motor neuropathy located in the LN domain.

Conclusions

Missense variants in exon 4 maybe correlated with epilepsy and variants in the LN domain maybe correlated with motor neuropathy in Chinese patients. Our study expands the clinical and genetic spectrum caused by LAMA2 variations and provides novel genotype-phenotype correlations of LGMD R23.
Brain effects of gestating germ-free persist in mouse neonates despite acquisition of a microbiota at birth
Authors: Castillo-Ruiz Alexandra , Gars Aviva , Sturgeon Hannah , Ronczkowski Nicole M. , Pyaram Dhanya N. , Dauriat Charlène J. G. , Chassaing Benoit , Forger Nancy G.
Published: May 2023

At birth, mammals experience a massive colonization by microorganisms. We previously reported that newborn mice gestated and born germ-free (GF) have increased microglial labeling and alterations in developmental neuronal cell death in the hippocampus and hypothalamus, as well as greater forebrain volume and body weight when compared to conventionally colonized (CC) mice. To test whether these effects are solely due to differences in postnatal microbial exposure, or instead may be programmed in utero, we cross-fostered GF newborns immediately after birth to CC dams (GF→CC) and compared them to offspring fostered within the same microbiota status (CC→CC, GF→GF). Because key developmental events (including microglial colonization and neuronal cell death) shape the brain during the first postnatal week, we collected brains on postnatal day (P) 7. To track gut bacterial colonization, colonic content was also collected and subjected to 16S rRNA qPCR and Illumina sequencing. In the brains of GF→GF mice, we replicated most of the effects seen previously in GF mice. Interestingly, the GF brain phenotype persisted in GF→CC offspring for almost all measures. In contrast, total bacterial load did not differ between the CC→CC and GF→CC groups on P7, and bacterial community composition was also very similar, with a few exceptions. Thus, GF→CC offspring had altered brain development during at least the first 7 days after birth despite a largely normal microbiota. This suggests that prenatal influences of gestating in an altered microbial environment programs neonatal brain development.
Dermoglandular advancement-rotation flap for conservative treatment of breast cancer – description of technique, objective and subjective assessments
Authors: Soliani Bastos Maria Carolina , Bagnoli Fábio , Rinaldi José Francisco , João Thais Businaro Fernandes , de Oliveira Vilmar Marques
Published: May 2023

Objective

to describe and evaluate the dermoglandular advancement-rotation flap with no contralateral surgery as a technique for the conservative treatment of breast cancer when skin or a large proportion of gland requires resection.

Patients/Methods

14 patients with breast tumors with a mean size of 4.2 cm and need for skin resection. The resection area is included within an isosceles triangle, with its apex located on the areola, which is the pivot for rotation of a dermoglandular flap released through a lateral extension along that triangle base. Symmetry before and after radiotherapy was objectively assessed by authors using the BCCT.core software, as well as subjectively by three experts and patients themselves using the Harvard scale.

Results

Experts considered the breast symmetry results to be excellent/good for 85.7% of patients in the early post-operative period and 78.6% in the late post-operative period. Excellent/good ratings provided by BCCT.core software amounted to 78.6% of cases in the early post-operative period and 92.9% in the late post-operative period. Symmetry was rated as excellent/good by 100% of patients.

Conclusion

Dermoglandular advancement-rotation flap technique with no contralateral surgery provides good symmetry when a large proportion of skin or gland requires resection on breast conservative cancer treatment.
TYROBP-positive endothelial cell-derived TWEAK as a promoter of osteosarcoma progression: insights from single-cell omics
Authors: Wei Zhi-qiang , Ding Sheng , Yang Yan-cai
Published: May 2023

Background

Endothelial cells (ECs) play a vital role in promoting the progression of malignant cells, and they exhibit heterogeneity in their phenotypic characteristics. We aimed to explore the initiating cells of ECs in osteosarcoma (OS) and investigate their potential interaction with malignant cells.

Method

We obtained scRNA-seq data from 6 OS patients, and datasets were batch-corrected to minimize variations among samples. Pseudotime analysis was performed to investigate the origin of differentiation of ECs. CellChat was employed to examine the potential communication between endothelial cells and malignant cells, and gene regulatory network analysis was performed to identify transcription factor activity changes during the conversion process. Importantly, we generated TYROBP-positive ECs in vitro and investigated its role in OS cell lines. Finally, we explored the prognosis of specific ECs cluster and their impact on the tumor microenvironment (TME) at the bulk transcriptome level.

Results

The results showed that TYROBP-positive ECs may play a crucial role in initiating the differentiation of ECs. TYROBOP-positive endothelial cells (ECs) exhibited the strongest crosstalk with malignant cells, likely mediated by TWEAK, a multifunctional cytokine. TYROBP-positive ECs exhibited significant expression of TME-related genes, unique metabolic and immunological profiles. Importantly, OS patients with low enrichment of TYROBP-positive ECs had better prognoses and a lower risk of metastasis. Finally, vitro assays confirmed that TWEAK was significantly increased in ECs-conditioned medium (ECs-CM) when TYROBP was over-expressed in EC cells, and could promote the proliferation and migration of OS cells.

Conclusion

We concluded that TYROBP-positive ECs may be the initiating cells and play a crucial role in the promotion of malignant cell progression. TYROBP-positive ECs have a unique metabolic and immunological profile and may interact with malignant cells through the secretion of TWEAK.
Animal venoms: a novel source of anti-Toxoplasma gondii drug candidates
Authors: Yang Dongqian , Liu Xiaohua , Li Jing , Xie Jing , Jiang Liping
Published: May 2023

Toxoplasma gondii (T. gondii) is a nucleated intracellular parasitic protozoan with a broad host selectivity. It causes toxoplasmosis in immunocompromised or immunodeficient patients. The currently available treatments for toxoplasmosis have significant side effects as well as certain limitations, and the development of vaccines remains to be explored. Animal venoms are considered to be an important source of novel antimicrobial agents. Some peptides from animal venoms have amphipathic alpha-helix structures. They inhibit the growth of pathogens by targeting membranes to produce lethal pores and cause membrane rupture. Venom molecules generally possess immunomodulatory properties and play key roles in the suppression of pathogenic organisms. Here, we summarized literatures of the last 15 years on the interaction of animal venom peptides with T. gondii and attempt to explore the mechanisms of their interaction with parasites that involve membrane and organelle damage, immune response regulation and ion homeostasis. Finally, we analyzed some limitations of venom peptides for drug therapy and some insights into their development in future studies. It is hoped that more research will be stimulated to turn attention to the medical value of animal venoms in toxoplasmosis.
Case report: Preemptive intervention for an infant with early signs of autism spectrum disorder during the first year of life
Authors: Colombi Costanza , Chericoni Natasha , Bargagna Stefania , Costanzo Valeria , Devescovi Raffaella , Lecciso Flavia , Pierotti Caterina , Prosperi Margherita , Contaldo Annarita
Published: May 2023

Autism spectrum disorder (ASD) includes neurodevelopmental conditions traditionally considered to bring life long disabilities, severely impacting individuals and their families. Very early identification and intervention during the very first phases of life have shown to significantly diminish symptom severity and disability, and improve developmental trajectories. Here we report the case of a young child showing early behavioral signs of ASD during the first months of life, including diminished eye contact, reduced social reciprocity, repetitive movements. The child received a pre-emptive parent mediated intervention based on the Infant Start, an adaptation of the Early Start Denver Model (ESDM), specifically developed for children with ASD signs during the first year of life. The child here described received intervention from 6 to 32 months of age, in combination with educational services. Diagnostic evaluations performed at several time points (8, 14, 19, and 32 months) showed progressive improvements in his developmental level and ASD symptoms. Our case study supports the possibility of identifying ASD symptoms and providing services as soon as concerns emerge even during the first year of life. Our report, in combination with recent infant identification and intervention studies, suggests the need for very early screening and preemptive intervention to promote optimal outcomes.
Combined associations of vitamin D and cognitive function with all-cause mortality among older adults in Chinese longevity areas: A prospective cohort study
Authors: Dai Miao , Song Quhong , Wang Xiang , Li Ying , Lin Taiping , Liang Rui , Jiang Tingting , Shu Xiaoyu , Ge Ning , Yue Jirong
Published: May 2023

Objectives

While both vitamin D deficiency and cognitive impairment have individually been linked to a greater risk of all-cause mortality, the combined effects of these two different conditions have not previously been explored in this context. We aimed to investigate the combined impact of vitamin D concentration and cognitive impairment on all-cause mortality in older adults.

Methods

The analyzed data were collected from community-dwelling adults ≥65 years of age that were enrolled in the Chinese Longitudinal Healthy Longevity Survey (n = 1,673). The Mini-Mental Status Examination (MMSE) was used to assess cognitive function, while the plasma 25-hydroxyvitamin D [25(OH)D] test was used to assess vitamin D status. The associations between vitamin D concentration, cognitive function, and all-cause mortality were assessed with Cox proportional hazards models. We used restricted cubic splines to examine the dose–response relationship between vitamin D and the risk of all-cause mortality and used joint effect testing to explore interactions between vitamin D concentration and cognitive function.

Results

During a mean (SD) follow-up of 3.8 (1.9) years, 899 (53.7%) deaths occurred. A negative dose–response relationship was observed between 25(OH)D concentration and cognition impairment at baseline, as well as the odds of all-cause mortality during follow-up. Similarly, cognitive impairment was significantly related to all-cause mortality risk (HR 1.81, 95% CI: 1.54 to 2.12). The combined analyses showed positive associations, with the highest mortality risk observed in older adults with both low vitamin D and cognitive impairment (HR 3.04, 95% CI: 2.40 to 3.86). Moreover, the interaction between 25(OH)D concentration and cognitive function was found to be significant in relation to the risk of mortality (p for interaction <0.001).

Conclusion

Lower plasma 25(OH)D and cognitive impairment were, respectively, associated with increased all-cause mortality risks. The 25(OH)D concentration and cognitive impairment exhibited a combined additive effect on all-cause mortality among older Chinese adults.
Recombinant mycobacterium tuberculosis fusion protein for diagnosis of mycobacterium tuberculosis infection: a short-term economic evaluation
Authors: Liu Zheng , Diao Sha , Zeng Linan , Liu Dan , Jiao Xuefeng , Chen Zhe , Cheng Xiao , Ni Xiaofeng , He Siyi , Wu Bin , Kang Deying , Wan Chaomin , Zhao Rongsheng , Wang Huiqing , Zhang Lingli
Published: May 2023

Objectives

Recombinant Mycobacterium tuberculosis fusion protein (EC) was anticipated to be used for the scale-up of clinical application for diagnosis of Mycobacterium tuberculosis infection in China, but it lacked a head-to-head economic evaluation based on the Chinese population. This study aimed to estimate the cost-utility and the cost-effectiveness of both EC and tuberculin pure protein derivative (TB-PPD) for diagnosis of Mycobacterium tuberculosis infection in the short term.

Methods

From a Chinese societal perspective, both cost-utility analysis and cost-effectiveness analysis were performed to evaluate the economics of EC and TB-PPD for a one-year period based on clinical trials and decision tree model, with quality-adjusted life years (QALYs) as the utility-measured primary outcome and diagnostic performance (including the misdiagnosis rate, the omission diagnostic rate, the number of patients correctly classified, and the number of tuberculosis cases avoided) as the effective-measured secondary outcome. One-way and probabilistic sensitivity analyses were performed to validate the robustness of the base-case analysis, and a scenario analysis was conducted to evaluate the difference in the charging method between EC and TB-PPD.

Results

The base-case analysis showed that, compared with TB-PPD, EC was the dominant strategy with an incremental cost-utility ratio (ICUR) of saving 192,043.60 CNY per QALY gained, and with an incremental cost-effectiveness ratio (ICER) of saving 7,263.53 CNY per misdiagnosis rate reduction. In addition, there was no statistical difference in terms of the omission diagnostic rate, the number of patients correctly classified, and the number of tuberculosis cases avoided, and EC was a similar cost-saving strategy with a lower test cost (98.00 CNY) than that of TB-PPD (136.78 CNY). The sensitivity analysis showed the robustness of cost-utility and cost-effectiveness analysis, and the scenario analysis indicated cost-utility in EC and cost-effectiveness in TB-PPD.

Conclusion

This economic evaluation from a societal perspective showed that, compared to TB-PPD, EC was likely to be a cost-utility and cost-effective intervention in the short term in China.
Associations of long-term exposure to air pollution, physical activity with blood pressure and prevalence of hypertension: the China Health and Retirement Longitudinal Study
Authors: Zhang Jinglong , Zhang Fen , Xin Chao , Duan Zhizhou , Wei Jing , Zhang Xi , Han Shichao , Niu Zhiping
Published: May 2023

Background

Long-term exposure to air pollution and physical activity (PA) are linked to blood pressure and hypertension. However, the joint effect of air pollution and PA on blood pressure and hypertension are still unknown in Chinese middle-aged and older adults.

Methods

A total of 14,622 middle-aged and older adults from the China Health and Retirement Longitudinal Study wave 3 were included in this study. Ambient air pollution [particulate matter with diameter ≤ 2.5 μm (PM2.5), or ≤10 μm (PM10), sulfur dioxide (SO2), nitrogen dioxide (NO2), carbonic oxide (CO)] were estimated using satellite-based spatiotemporal models. PA was investigated using International Physical Activity Questionnaire. Generalized linear models were used to examine the associations of air pollution, PA score with blood pressure [systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP)], and the prevalence of hypertension. Subgroup analysis was conducted to investigate the effects of air pollution on blood pressure and the prevalence of hypertension in different PA groups.

Results

The results showed that for each inter-quartile range (IQR) increase in PM2.5 (25.45 μg/m3), PM10 (40.56 μg/m3), SO2 (18.61 μg/m3), NO2 (11.16 μg/m3), CO (0.42 mg/m3) and PA score (161.3 MET/h-week), the adjusted odd ratio (OR) of hypertension was 1.207 (95% confidence interval (CI): 1.137, 1.281), 1.189 (95%CI: 1.122, 1.260), 1.186 (95%CI: 1.112, 1.266), 1.186 (95%CI: 1.116, 1.260), 1.288 (95%CI: 1.223, 1.357), 0.948 (95%CI: 0.899, 0.999), respectively. Long-term exposure to PM2.5, PM10, SO2, NO2, and CO was associated with increased SBP, DBP, and MAP levels. For example, each IQR increase in PM2.5 was associated with 1.20 mmHg (95%CI: 0.69, 1.72) change in SBP, 0.66 mmHg (95%CI: 0.36, 0.97) change in DBP, and 0.84 mmHg (95%CI: 0.49, 1.19) change in MAP levels, respectively. Each IQR increase in PA score was associated with −0.56 mmHg (95%CI: −1.03, −0.09) change in SBP, −0.32 mmHg (95%CI: −0.59, −0.05) change in DBP, and −0.33 mmHg (95%CI: −0.64, −0.02) change in MAP levels, respectively. Subgroup analysis found that the estimated effects in the sufficient PA group were lower than that in the insufficient PA group.

Conclusion

Long-term exposure to air pollutants is associated with increased blood pressure and hypertension risk, while high-level PA is associated with decreased blood pressure and hypertension risk. Strengthening PA might attenuate the adverse effects of air pollution on blood pressure and hypertension risk.
Nitrous oxide: a unique official French addictovigilance national survey
Authors: Guerlais Marylène , Aquizerate Aurélie , Lionnet Arthur , Daveluy Amélie , Duval Mélanie , Gérardin Marie , Istvan Marion , Laforgue Edouard-Jules , Victorri-Vigneau Caroline ,   for French Addictovigilance Network
Published: May 2023

Introduction

Nitrous oxide has become over the last few years a public health problem in many countries. France has a dedicated health monitoring system dedicated to the surveillance of the abuse, dependence and consequences associated with the use of psychoactive substances coordinated by the French National Agency for the Safety of Medicines and Health Products.

We present the French national survey of nitrous oxide.

Materials and methods

We analyzed all the cases with nitrous oxide from 2012 to 2021: number of notifications, characteristics of the subjects and consumption, consequences reported and their evolutions over time. In addition, we have made a special focus on the four main complications reported.

Results

A total of 525 cases were received with an exponential increase since 2019. We observed changes in the characteristics of the notifications with an increase in the proportion of women [42.7% in 2021 vs. 30.8% in 2020 (p = 0.02)]; an increase in the quantities consumed (use of cylinders); a negative evolution of the contexts of use with a search for self-therapeutic effects and use in violent contexts; an increasing trend of the severity of cases [78.1% in 2021 vs. 70.0% in 2020 (p = 0.07)].

The main effects were substance use disorders and/or associated criteria (82.5%), neurological disorders (75.4%), psychiatric symptoms (15.4%) and cardiovascular events (8.6%). In terms of evolution, we observed a significant increase in cases with a use disorder and an increase in neurological complications. Moreover, new serious effects, notably cardiovascular events were reported.

Discussion

The combination of high availability, varied effects from euphoria to relief of discomfort in a stressful global pandemic context and the development of dependence could explain the rapid growth of consumption and the seriousness of the cases.

It must now be taken into account that (i) Substance use disorders are associated with nitrous oxide consumption; (ii) clinicians must consider “nitrous oxide” in young subjects presenting different types of manifestations; and (iii) stopping consumption is imperative and is the first treatment. In this context, an addictological assessment must also be carried out.