bluuebunny/crossref_metadata_2025 huggingface dataset:
Fighting misinformation in seismology: Expert opinion on earthquake facts vs. fiction
Authors: Dryhurst Sarah , Mulder Femke , Dallo Irina , Kerr John R. , McBride Sara K. , Fallou Laure , Becker Julia S.
Published: December 2022

Misinformation carries the potential for immense damage to public understanding of science and for evidence-based decision making at an individual and policy level. Our research explores the following questions within seismology: which claims can be considered misinformation, which are supported by a consensus, and which are still under scientific debate? Consensus and debate are important to quantify, because where levels of scientific consensus on an issue are high, communication of this fact may itself serve as a useful tool in combating misinformation. This is a challenge for earthquake science, where certain theories and facts in seismology are still being established. The present study collates a list of common public statements about earthquakes and provides–to the best of our knowledge–the first elicitation of the opinions of 164 earth scientists on the degree of verity of these statements. The results provide important insights for the state of knowledge in the field, helping identify those areas where consensus messaging may aid in the fight against earthquake related misinformation and areas where there is currently lack of consensus opinion. We highlight the necessity of using clear, accessible, jargon-free statements with specified parameters and precise wording when communicating with the public about earthquakes, as well as of transparency about the uncertainties around some issues in seismology.
Identification of small molecules as novel anti-adipogenic compounds based on Connectivity Map
Authors: Zhang Shuang , Lyons Nicholas , Koedam Marijke , van de Peppel Jeroen , van Leeuwen Johannes P.T.M. , van der Eerden Bram C. J.
Published: December 2022

Several physiological and pathological conditions such as aging, obesity, diabetes, anorexia nervosa are associated with increased adipogenesis in the bone marrow. A lack of effective drugs hinder the improved treatment for aberrant accumulation of bone marrow adipocytes. Given the higher costs, longer duration and sometimes lack of efficacy in drug discovery, computational and experimental strategies have been used to identify previously approved drugs for the treatment of diseases, also known as drug repurposing. Here, we describe the method of small molecule-prioritization by employing adipocyte-specific genes using the connectivity map (CMap). We then generated transcriptomic profiles using human mesenchymal stromal cells under adipogenic differentiation with the treatment of prioritized compounds, and identified emetine and kinetin-riboside to have a potent inhibitory effect on adipogenesis. Overall, we demonstrated a proof-of-concept method to identify repurposable drugs capable of inhibiting adipogenesis, using the Connectivity Map.
Sacubitril/Valsartan contributes to improving the diabetic kidney disease and regulating the gut microbiota in mice
Authors: Wang Peipei , Guo Ruixue , Bai Xiwen , Cui Wen , Zhang Yiding , Li Huangmin , Shang Jin , Zhao Zhanzheng
Published: December 2022

Background

Diabetic kidney disease (DKD), as a serious microvascular complication of diabetes, has limted treatment options. It is reported that the Sacubitril/Valsartan (Sac/Val) can improve kidney function, and the disordered gut microbiota and part of its metabolites are related to the development of DKD. Therefore, we aim to explore whether the effect of Sac/Val on DKD is associated with the gut microbiota and related plasma metabolic profiles.

Methods

Male C57BL/6J mice were randomly divided into 3 groups: Con group (n = 5), DKD group (n = 6), and Sac/Val group (n = 6) . Sac/Val group was treated with Sac/Val solution. The intervention was given once every 2 days for 6 weeks. We measured the blood glucose and urine protein level of mice at different times. We then collected samples at the end of experiment for the 16s rRNA gene sequencing analysis and the untargeted plasma metabonomic analysis.

Results

We found that the plasma creatinine concentration of DKD-group mice was significantly higher than that of Con-group mice, whereas it was reduced after the Sac/Val treatment. Compared with DKD mice, Sac/Val treatment could decrease the expression of indicators related to EndMT and renal fibrosis like vimentin, collagen IV and fibronectin in kidney. According to the criteria of LDA ≥ 2.5 and p<0.05, LefSe analysis of gut microbiota identified 13 biomarkers in Con group, and 33 biomarkers in DKD group, mainly including Prevotella, Escherichia_Shigella and Christensenellaceae_R_7_group, etc. For the Sac/Val group, there were 21 biomarkers, such as Bacteroides, Rikenellaceae_RC9_gut_group, Parabacteroides, Lactobacillus, etc. Plasma metabolomics analysis identified a total of 648 metabolites, and 167 important differential metabolites were screened among groups. KEGG pathway of tryptophan metabolism: M and bile secretion: OS had the highest significance of enrichment.

Conclusions

Sac/Val improves the renal function of DKD mice by inhibiting renal fibrosis. This drug can also regulate gut microbiota in DKD mice.
The usefulness of serial ultrasound in thyroid mucosa-associated lymphoid tissue lymphoma
Authors: Zhang Xiumei , Wei Boxiong , Nong Lin , Zhang Hong , Gao Ying , Ou Jinping
Published: December 2022

Background

Mucosa-associated lymphoid tissue (MALT) lymphoma is an extranodal lymphoma with an indolent natural course. The thyroid gland is an uncommon site of involvement. We aimed to investigate serial ultrasound features and the disease progression during the clinical course of thyroid MALT lymphoma.

Methods

We searched our hospital’s pathology database (5,418 patients with thyroid malignancy) between January 2000 and July 2022. The medical records and serial ultrasounds of 11 patients with 12 thyroid MALT lymphoma foci were analyzed retrospectively.

Results

An enlarging neck mass, dyspnea, B symptoms, and neck lymphadenopathy were seen at diagnosis in 9 (9/11, 81.8%), 3 (3/11, 27.3%), 2 (2/11, 18.2%), and 9 (9/11, 81.8%) cases, respectively. Eleven cases were concomitant Hashimoto thyroiditis. Common ultrasound features included bilateral or unilateral asymmetric goiter or large, solid, and very hypoechoic nodules (11/12, 91.7%) interspersed with linear, reticular hyperechoic, and enhanced posterior echoes (11/12, 91.7%), and neck lymph node involvement (10/11, 90.9%). The Thyroid Imaging and Reporting Data System (TIRADS) categories showed higher diagnostic accuracy (11/12, 91.7%) than real-time ultrasound (2/12, 16.7%) in evaluating thyroid lesions for recommendation of fine-needle aspiration (FNA). Serial ultrasound showed self-limiting changes in three cases, relapse in three cases after subtotal thyroidectomy and chemotherapy, large cell transformation (LCT) in one case after left lobectomy, partial remission in one case, and complete remission after chemo/radiation in four cases; progression to enlarged thyroid nodules occurred in three cases without treatment, with no obvious change observed after diagnosis. Three patients died during follow-up.

Conclusion

On sonograms, solid large thyroid nodules or goiter with very hypoechoic and enhanced posterior echoes in the setting of Hashimoto thyroiditis should raise suspicion for MALT lymphoma. TIRADS categories can improve the ultrasound diagnostic efficacy for malignancy. Serial ultrasound examinations demonstrated self-limiting and indolent natures of thyroid MALT lymphoma.
Time-restricted feeding improves metabolic and endocrine profiles in mice with polycystic ovary syndrome
Authors: Han Yan , Lin Baiwei , Lu Wenjing , Wang Xu , Tang Wenshuai , Tao Xinge , Cai Han , He Chunmei , Liu Changqin
Published: December 2022

Objectives

Polycystic ovary syndrome (PCOS) is one of the most common endocrinopathy disorders in premenopausal women, which is characterized by hyperandrogenemia, anovulation, and polycystic ovarian morphology (PCOM). Time-restricted feeding (TRF) is a new intermittent restriction dietary pattern, which has been shown to have positive benefits on obesity and glycolipid metabolism disorders. We aimed to explore the effect of the feeding regimen (ad libitum vs. TRF) on the glycolipid metabolism and reproductive endocrine disorders in a PCOS mouse model.

Methods

PCOS mouse model was induced by continuous subcutaneous administration of dihydrotestosterone for 21 days. Mice were fed a high-fat diet (HFD) for 8 weeks on an ad libitum or time- restricted diet (from 10:30 p.m. to 6:30 a.m.).

Results

Compared to control mice, PCOS mice that received TRF treatment had significantly lower body weight, reduced adiposity, lower area under the curve (AUC) of glucose response in the oral glucose tolerance test (OGTT), and lower AUC in the insulin tolerance test (ITT). TRF also ameliorated lipid metabolism, as shown by a reduction in plasma lipid profiles (triglycerides and cholesterol) and the triglyceride content in the liver of PCOS mice. In terms of reproduction, the plasma androgen level, plasma estrogen (E2) level, and luteinizing hormone (LH)/follicle stimulating hormone (FSH) ratio in PCOS mice were significantly reduced after 8 weeks of TRF treatment. In addition, ovarian histology showed that TRF inhibits cyst formation and promotes corpus luteum formation.

Conclusion

In conclusion, TRF improved metabolic and endocrine profiles in mice with PCOS.
Gene mutations associated with fertilization failure after in vitro fertilization/intracytoplasmic sperm injection
Authors: Xue Yamei , Cheng Xiaohong , Xiong Yuping , Li Kun
Published: December 2022

Fertilization failure during assisted reproductive technologies (ART) is often unpredictable, as this failure is encountered only after in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) have been performed. The etiology of fertilization failure remains elusive. More and more mutations of genes are found to be involved in human fertilization failure in infertile patients as high throughput sequencing techniques are becoming widely applied. In this review, the mutations of nine important genes expressed in sperm or oocytes, PLCZ1, ACTL7A, ACTL9, DNAH17, WEE2, TUBB8, NLRP5, ZP2, and TLE6, were summarized and discussed. These abnormalities mainly have shown Mendelian patterns of inheritance, including dominant and recessive inheritance, although de novo mutations were present in some cases. The review revealed the crucial roles of each reported gene in the fertilization process and summarized all known mutations and their corresponding phenotypes. The review suggested the mutations might become promising targets for precision treatments in reproductive medicine. Moreover, our work will provide some helpful clues for genetic counseling, risk prediction, and optimizing clinical treatments for human infertility by supplying the useful and timely information on the genetic causes leading to fertilization failure.
Delineating the molecular landscape of different histopathological growth patterns in colorectal cancer liver metastases
Authors: Hu Mingtao , Chen Zhigang , Hu Dandan , Xi Shaoyan , Wang Deshen , Zhang Xiaolong , Fong William Pat , Wen Lei , Cai Yanyu , Yuan Yunfei , Li Binkui , Wu Xiaojun , Lu Zhenhai , Chen Gong , Li Liren , Ding Peirong , Pan Zhizhong , Wan Desen , Du Ziming , Chen Minshan , Li Yuhong
Published: December 2022

Background

Histopathological growth patterns (HGPs) have shown important prognostic values for patients with colorectal cancer liver metastases, but the potential molecular mechanisms remain largely unknown.

Methods

We performed an exploratory analysis by conducting the RNA sequencing of primary colorectal lesions, colorectal liver metastatic lesions and normal liver tissues.

Findings

We found that desmoplastic HGPs of the metastatic lesions were significantly enriched in EMT, angiogenesis, stroma, and immune signaling pathways, while replacement HGPs were enriched in metabolism, cell cycle, and DNA damage repair pathways. With the exception of immune-related genes, the differentially expressed genes of the two HGPs from colorectal liver metastases were mostly inherited from the primary tumor. Moreover, normal liver tissue in the desmoplastic HGP subgroup was markedly enriched in the fibrinous inflammation pathway.

Conclusions

We surmised that HGPs are observable morphological changes resulting from the regulation of molecular expressions, which is the combined effect of the heterogeneity and remodeling of primary tumors seeds and liver soils.
Detrimental effects of simulated microgravity on mast cell homeostasis and function
Authors: Kim Minjin , Jang Gyeongin , Kim Kyu-Sung , Shin Jinwook
Published: December 2022

Exposure to microgravity causes significant alterations in astronauts’ immune systems during spaceflight; however, it is unknown whether microgravity affects mast cell homeostasis and activation. Here we show that microgravity negatively regulates the survival and effector function of mast cells. Murine bone marrow-derived mast cells (BMMCs) were cultured with IL-3 in a rotary cell culture system (RCCS) that generates a simulated microgravity (SMG) environment. BMMCs exposed to SMG showed enhanced apoptosis along with the downregulation of Bcl-2, and reduced proliferation compared to Earth’s gravity (1G) controls. The reduction in survival and proliferation caused by SMG exposure was recovered by stem cell factor. In addition, SMG impaired mast cell degranulation and cytokine secretion. BMMCs pre-exposed to SMG showed decreased release of β-hexosaminidase, interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) upon stimulation with phorbol 12-myristate-13-acetate (PMA) plus calcium ionophore ionomycin, which correlated with decreased calcium influx. These findings provide new insights into microgravity-mediated alterations of mast cell phenotypes, contributing to the understanding of immune system dysfunction for further space medicine research.
Pasteurella multocida toxin – lessons learned from a mitogenic toxin
Authors: Kubatzky Katharina F.
Published: December 2022

The gram-negative, zoonotic bacteriumPasteurella multocidawas discovered in 1880 and found to be the causative pathogen of fowl cholera.Pasteurella-related diseases can be found in domestic and wild life animals such as buffalo, sheep, goat, deer and antelope, cats, dogs and tigers and cause hemorrhagic septicemia in cattle, rhinitis or pneumonia in rabbits or fowl cholera in poultry and birds.Pasteurella multocidadoes not play a major role in the immune-competent human host, but can be found after animal bites or in people with close contact to animals. Toxigenic strains are most commonly found in pigs and express a phage-encoded 146 kDa protein, thePasteurella multocidatoxin (PMT). Toxin-expressing strains cause atrophic rhinitis where nasal turbinate bones are destroyed through the inhibition of bone building osteoblasts and the activation of bone resorbing osteoclasts. After its uptake through receptor-mediated endocytosis, PMT specifically targets the alpha subunit of several heterotrimeric G proteins and constitutively activates them through deamidation of a glutamine residue to glutamate in the alpha subunit. This results in cytoskeletal rearrangement, proliferation, differentiation and survival of cells. Because of the toxin’s mitogenic effects, it was suggested that it might have carcinogenic properties, however, no link betweenPasteurellainfections and cell transformation could be established, neither in tissue culture models nor through epidemiological data. In the recent years it was shown that the toxin not only affects bone, but also the heart as well as basically all cells of innate and adaptive immunity. During the last decade the focus of research shifted from signal transduction processes to understanding how the bacteria might benefit from a bone-destroying toxin. The primary function of PMT seems to be the modulation of immune cell activation which at the same time creates an environment permissive for osteoclast formation. While the disease is restricted to pigs, the implications of the findings from PMT research can be used to explore human diseases and have a high translational potential. In this review our current knowledge will be summarized and it will be discussed what can be learned from using PMT as a tool to understand human pathologies.
Issues occupying our minds: Nomenclature of autoimmune blistering diseases requires updating, pemphigus vulgaris propensity to affect areas adjacent to natural body orifices unifies seemingly diverse clinical features of this disease
Authors: Dmochowski Marian , Jałowska Magdalena , Bowszyc-Dmochowska Monika
Published: December 2022

In this conceptual analysis, we present our concepts on two issues regarding autoimmune bullous diseases (AIBD), namely (i) current nomenclature of AIBD requires updating by incorporating molecular data and (ii) pemphigus vulgaris (PV) “likes” areas adjacent to natural body orifices. The problem of inadequacy of the currently used nomenclature was noticed recently by Zillikens, who proposed to form a group with the task of updating it. The early efforts by Dmochowski to update this nomenclature happened to be a daunting task. Nevertheless, the ideal nomenclature should retain the bulk of clinical data, which generations of dermatologists are accustomed to, including triggers if known, and incorporate molecular data revealing targets of autoimmune response and immunoglobulin isotypes involved. The natural body orifices affected by PV were previously described in numerous publications. However, these openings are described separately in these publications. Here, Dmochowski comes up with an intellectual concept that this propensity of PV unifies seemingly diverse clinical features of this disease.
Are we overlooking Natura 2000 sites? Lessons learned from a transnational project in the Adriatic Sea
Authors: Gianni Fabrizio , Manea Elisabetta , Cataletto Bruno , Pugnetti Alessandra , Bergami Caterina , Bongiorni Lucia , Pleslić Grgur , Vilibić Ivica , Bandelj Vinko
Published: December 2022

Since the adoption of the Habitats and Birds Directives by EU governments, marine Natura 2000 (N2K) sites have been established in the European Mediterranean Sea, creating one of the largest international networks of protected areas. Nevertheless, to date, marine N2K sites are generally scarcely implemented, studied and monitored, and thus their management effectiveness is weak, and their environmental status is often unknown. The Interreg Italy-Croatia ECOSS project aimed at establishing the ECOlogical observing system of the Adriatic Sea (ECOAdS), to integrate the existing research and monitoring activities in the area, and to promote data sharing at international level, for enhancing monitoring and conservation in Adriatic N2K network. In the framework of ECOSS, a conceptual model was developed and applied to selected N2K sites, to review the existing knowledge, assess site effectiveness, and suggest possible improvements in their monitoring and management based on the contribution that ECOAdS can provide to their implementation. Information on social, ecological, and oceanographic elements related to the conservation and management of these case studies was gathered by consulting the project partners involved in the management and monitoring of the sites and through a literature review. The results of this study revealed a discouraging condition with no management plan in most of the sites, while regulatory measures are generally in place but without surveillance. Monitoring activities are performed occasionally, and information on presence and status of protected species is often lacking or outdated. Although the N2K network provides a unique opportunity to advance marine conservation and achieve the 30% conservation target by 2030, the biggest challenge ahead is the proper management and monitoring of N2K sites. The proposed conceptual model may be taken as a framework to properly set up ecological observing systems in the N2K network and help overcome current limitations, integrating scientific research within the N2K conservation strategies.
Mitigating effects of sea-level rise on maritime features through the international law-making process in the Law of the Sea
Authors: Chen Xidi , Xu Qi
Published: December 2022

Sea-level rise is not only causing physical damage to maritime features but also posing challenges to the law of the sea. The United Nations Convention on the Law of the Sea lends legal significance to the relative position of the land and the sea. However, the ecological situation of maritime features and rising sea levels are changing these factors and placing the legal status of these features at risk of reclassification. This implies that islands with full rights may lose their exclusive economic zones, continental shelves, and even territorial seas due to sea-level rise. In addition to the physical enhancement of maritime features, legal solutions, as a more sustainable and affordable approach, are expected to contribute to mitigating adverse impacts of sea-level rise. However, most discussions are limited to the issue of baselines and maritime boundaries, while the legal status of maritime features has not received sufficient attention. In this paper, we examine in detail the limitations of existing laws, particularly the Convention, and present substantive and procedural options for the establishment of new rules to mitigate the effects of sea-level rise. The legal impacts of sea-level rise on maritime features can be categorized into three different aspects: dynamics of the relative position of land and sea, ecological degradation, and human interventions. It was found that the current international rules are insufficiently flexible in addressing the challenges posed by sea-level rise; thus, international law-making is therefore considered necessary. As far as the proposed rule is concerned, either legally “sustaining” the status of maritime features or allowing reclassification elicits complex issues, particularly considering the close connection between land and maritime zones under the law of the sea. Moreover, attempts to achieve new rules by applying any procedural option for international law-making in isolation may be impractical. In light of this, we explore a viable approach to the progressive development of relevant legal regimes, following the international community’s optimal consensus and shared interests.
Oceanic productivity and high-frequency temperature variability—not human habitation—supports calcifier abundance on central Pacific coral reefs
Authors: Huntington Brittany , Vargas-Ángel Bernardo , Couch Courtney S. , Barkley Hannah C. , Abecassis Melanie
Published: December 2022

Past research has demonstrated how local-scale human impacts—including reduced water quality, overfishing, and eutrophication—adversely affect coral reefs. More recently, global-scale shifts in ocean conditions arising from climate change have been shown to impact coral reefs. Here, we surveyed benthic reef communities at 34 U.S.-affiliated Pacific islands spanning a gradient of oceanic productivity, temperature, and human habitation. We re-evaluated patterns reported for these islands from the early 2000s in which uninhabited reefs were dominated by calcifiers (coral and crustose coralline algae) and thought to be more resilient to global change. Using contemporary data collected nearly two decades later, our analyses indicate this projection was not realized. Calcifiers are no longer the dominant benthic group at uninhabited islands. Calcifier coverage now averages 26.9% ± 3.9 SE on uninhabited islands (compared to 45.18% in the early 2000s). We then asked whether oceanic productivity, past sea surface temperatures (SST), or acute heat stress supersede the impacts of human habitation on benthic cover. Indeed, we found variation in benthic cover was best explained not by human population densities, but by remotely sensed metrics of chlorophyll-a, SST, and island-scale estimates of herbivorous fish biomass. Specifically, higher coral and CCA cover was observed in more productive waters with greater biomass of herbivores, while turf cover increased with daily SST variability and reduced herbivore biomass. Interestingly, coral cover was positively correlated with daily variation in SST but negatively correlated with monthly variation. Surprisingly, metrics of acute heat stress were not correlated with benthic cover. Our results reveal that human habitation is no longer a primary correlate of calcifier cover on central Pacific island reefs, and highlight the addition of oceanic productivity and high-frequency SST variability to the list of factors supporting reef builder abundance.
Secondary consolidation characteristics of organic soil modified by bio-enzyme based on the Gibson model
Authors: Zhang Yixin , Wen Changping
Published: December 2022

In order to study the secondary consolidation characteristics of organic soil improved by bio-enzyme, the secondary consolidation test was carried out. First, the Gibson rheological model parameters were fitted according to the experimental results. Then, the relationship between rheological model parameters, Ca/Cc value, secondary consolidation coefficient Ca, and load was analyzed for different ratios of bio-enzyme. The results showed that: 1) the rheological model parameters were negatively correlated with the ratios of bio-enzyme and positively correlated with the load value. The rheological model parameters E1 (Kelvin elastic modulus) and η (Kelvin viscosity coefficient) reached the maximum value when the ratio of bio-enzyme was 0.01%. 2) The secondary consolidation coefficient was related to the load and showed a certain law. At 100 kPa, the secondary consolidation coefficient of samples reached the peak. When it was less than 200 kPa, the secondary consolidation coefficient changed obviously with the increase in load. When the load was greater than 200 kPa, the variation trend of the secondary consolidation coefficient tended to be gentle with the increase in load and finally tended to be constant. With the increase in load, the secondary consolidation coefficient Ca finally approached to a stable value. 3) The value of Ca/Cc of improved organic soil varied from 0.042 to 0.1 under various loads. In this article, the secondary consolidation characteristics of organic soil modified by bio-enzyme were studied. The secondary consolidation strain can be predicted by the established rheological model parameter equations.
Optimization design and performance evaluation of a novel asphalt rejuvenator
Authors: Yi Jiao , Yuanguang Xie , Zhengjia Liu
Published: December 2022

The development of a regeneration agent is one of the key technologies for pavement regeneration and one of the methods to reduce carbon emissions in the transportation field, so it is very necessary to develop a regeneration agent. Based on the composition of asphalt and rejuvenator components, the optimal dosing of extraction oil, plasticizer dioctyl phthalate (DOP), and hydrogenated (carbon 9) C9 petroleum resin was determined by the response surface method, and the suitable dosing of the anti-aging agent was also designed to optimize the orthogonal experiment to prepare the ZJ-I (Zenith Yummy-Invent) rejuvenator with good overall performance. On the basis of the ZJ-I rejuvenator, dynamic shear rheology (DSR), bending beam rheometery (BBR), Fourier transform infrared spectroscopy (FTIR), atomic force microscopy (AFM), and contact angle experiments were used to investigate the effects of the ZJ-I rejuvenator dosing on the high- and low-temperature rheology, chemical structure, surface microscopic morphology, and adhesion between asphalt and aggregate of aged asphalt and to explore the regeneration effect and regeneration mechanism of the ZJ-I rejuvenator. The results showed that the ZJ-I rejuvenator formulated with 83.6% extracted oil, 15% plasticizer DOP, 1.4% hydrogenated petroleum resin, 0.6% antioxidant, and 0.4% light stabilizer has the best regeneration effect, and its optimal dosing is 7% aging degree. It can also improve the adhesion performance of asphalt and aggregate.
Cyclic di-GMP regulates bacterial colonization and further biocontrol efficacy of Bacillus velezensis against apple ring rot disease via its potential receptor YdaK
Authors: Gong Huiling , Jiang Wenxiao , Yang Yang , Zhang Yue , Chen Xufei , Li Wei , Yang Panlei , Wang Zhenshuo , Wang Qi , Li Yan
Published: December 2022

Bacillus species are among the most investigated beneficial bacteria and widely used in agricultural systems as biological control agents. Its biocontrol efficacy is controlled by diverse regulators. Cyclic diguanylate (c-di-GMP) is a nearly universal second messenger in bacteria and modulates various important physiological processes, including motility, biofilm formation, antifungal antibiotic production and host colonization. However, the impact of c-di-GMP on biocontrol efficacy of beneficial bacteria is unknown. Bacillus velezensis PG12 is an effective biocontrol strain against apple ring rot disease caused by Botryosphaeria dothidea. In this study, the contribution of c-di-GMP to biocontrol efficacy of B. velezensis PG12 was investigated. Deletion of single gene encoding diguanylate cyclase or phosphodiesterase did not affect its biocontrol efficacy against apple ring rot. However, artificial modulation of c-di-GMP level in the cells leads to a significant change of biocontrol efficacy, suggesting that c-di-GMP positively regulates biocontrol efficacy of B. velezensis PG12 against apple ring rot disease. More evidences indicate that c-di-GMP does not affect the antagonistic activity of B. velezensis PG12 against B. dothidea in vitro and in vivo, but positively regulates biofilm formation of B. velezensis PG12 and its colonization on apple fruits. Importantly, deletion of ydaK could rescue the inhibition of biofilm formation, bacterial colonization and biocontrol efficacy caused by low c-di-GMP level, indicating that YdaK is the potential c-di-GMP receptor to regulate biofilm formation, colonization and effective biological control. However, YdaK did not affect the antagonistic activity of B. velezensis PG12 against B. dothidea. Based on these findings, we propose that c-di-GMP regulates biofilm formation, subsequently the bacterial colonization on apple fruits and thus biocontrol efficacy of B. velezensis through its receptor YdaK. This is the first report showing that c-di-GMP plays a role in biocontrol efficacy of beneficial bacteria.
Biocrusts from Iceland and Svalbard: Does microbial community composition differ substantially?
Authors: Pushkareva Ekaterina , Elster Josef , Holzinger Andreas , Niedzwiedz Sarina , Becker Burkhard
Published: December 2022

A wide range of microorganisms inhabit biocrusts of arctic and sub-arctic regions. These taxa live and thrive under extreme conditions and, moreover, play important roles in biogeochemical cycling. Nevertheless, their diversity and abundance remain ambiguous. Here, we studied microbial community composition in biocrusts from Svalbard and Iceland using amplicon sequencing and epifluorescence microscopy. Sequencing of 16S rRNA gene revealed the dominance of Chloroflexi in the biocrusts from Iceland and Longyearbyen, and Acidobacteria in the biocrusts from Ny-Ålesund and South Svalbard. Within the 18S rRNA gene sequencing dataset, Chloroplastida prevailed in all the samples with dominance of Trebouxiophyceae in the biocrusts from Ny-Ålesund and Embryophyta in the biocrusts from the other localities. Furthermore, cyanobacterial number of cells and biovolume exceeded the microalgal in the biocrusts. Community compositions in the studied sites were correlated to the measured chemical parameters such as conductivity, pH, soil organic matter and mineral nitrogen contents. In addition, co-occurrence analysis showed the dominance of positive potential interactions and, bacterial and eukaryotic taxa co-occurred more frequently together.
Cerebrospinal fluid neurofilament dynamic profiles predict cognitive progression in individuals with de novo Parkinson’s disease
Authors: Sheng Ze-Hu , Ma Ling-Zhi , Liu Jia-Yao , Ou Ya-Nan , Zhao Bing , Ma Ya-Hui , Tan Lan
Published: December 2022

Background

Neurofilament light chain protein (NfL) in cerebrospinal fluid (CSF) reflects the severity of neurodegeneration, with its altered concentrations discovered in Parkinson’s disease (PD) and Parkinson’s disease dementia (PD-D).

Objective

To determine whether CSF NfL, a promising biomarker of neuronal/axonal damage, can be used to monitor cognitive progression in de novo Parkinson’s disease and predict future cognitive decline.

Methods

A total of 259 people were recruited in this study, including 85 healthy controls (HC) and 174 neonatal PD patients from the Parkinson’s Progression Markers Initiative (PPMI). Multiple linear regression and linear mixed effects models were used to examine the associations of baseline/longitudinal CSF NfL with cognitive decline and other CSF biomarkers. Kaplan–Meier analysis and log-rank test were used to compare the cumulative probability risk of cognition progression during the follow-up. Multivariate cox regression was used to detect cognitive progression in de novo PD.

Results

We found PD patients with mild cognitive impairment (PD-MCI) was higher than with normal cognition (PD-NC) in terms of CSF NfL baseline levels (p = 0.003) and longitudinal increase rate (p = 0.034). Both baseline CSF NfL and its rate of change predicted measurable cognitive decline in de novo PD (MoCA, β = −0.010, p = 0.011; β = −0.0002, p < 0.001, respectively). The predictive effects in de novo PD patients aged >65, male, ill-educated (<13 years) and without carrying Apolipoprotein E ε4 (APOE ε4) seemed to be more obvious and reflected in more domains investigated. We also observed that CSF NfL levels predicted progression in de novo PD patients with different cognitive diagnosis and amyloid status. After an average follow-up of 6.66 ± 2.54 years, higher concentration above the median of baseline CSF NfL was associated with a future high risk of PD with dementia (adjusted HR 2.82, 95% CI: 1.11–7.20, p = 0.030).

Conclusion

Our results indicated that CSF NfL is a promising prognostic predictor of PD, and its concentration and dynamics can monitor the severity and progression of cognitive decline in de novo PD patients.
Association of platelet-to-lymphocyte ratio and neutrophil-to-lymphocyte ratio with outcomes in stroke patients achieving successful recanalization by endovascular thrombectomy
Authors: Ma Jin , Guo Wenting , Xu Jiali , Li Sijie , Ren Changhong , Wu Longfei , Wu Chuanjie , Li Chuanhui , Chen Jian , Duan Jiangang , Ma Qingfeng , Song Haiqing , Zhao Wenbo , Ji Xunming
Published: December 2022

Objective

Serum inflammatory biomarkers play crucial roles in the development of acute ischemic stroke (AIS). In this study, we explored the association between inflammatory biomarkers including platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), and monocyte-to-lymphocyte ratio (MLR), and clinical outcomes in AIS patients who achieved successful recanalization.

Methods

Patients with AIS who underwent endovascular thrombectomy (EVT) and achieved a modified thrombolysis in the cerebral infarction scale of 2b or 3 were screened from a prospective cohort at our institution between January 2013 and June 2021. Data on blood parameters and other baseline characteristics were collected. The functional outcome was an unfavorable outcome defined by a modified Rankin Scale of 3–6 at the 3-month follow up. Other clinical outcomes included symptomatic intracranial hemorrhage (sICH) and 3-month mortality. Multivariable logistic regression analysis was performed to evaluate the effects of PLR, NLR, and MLR on clinical outcomes.

Results

A total of 796 patients were enrolled, of which 89 (11.2%) developed sICH, 465 (58.4%) had unfavorable outcomes at 3 months, and 168 (12.1%) died at the 3-month follow up. After adjusting for confounding variables, a higher NLR (OR, 1.076; 95% confidence interval [CI], 1.037–1.117; p < 0.001) and PLR (OR, 1.001; 95%CI, 1.000–1.003; p = 0.045) were significantly associated with unfavorable outcomes, the area under the receiver operating characteristic curve of NLR and PLR was 0.622 and 0.564, respectively. However, NLR, PLR, and MLR were not independently associated with sICH and 3-month mortality (all adjusted p > 0.05).

Conclusion

Overall, our results indicate that higher PLR and NLR were independently associated with unfavorable functional outcomes in AIS patients with successful recanalization after EVT; however, the underlying mechanisms are yet to be elucidated.
Multiplex detection of meningitis and encephalitis pathogens: A study from laboratory to clinic
Authors: Si Yanjun , He Weijun , Guo Shuo , Wang Xiaohui , Tang Meng , Ying Binwu , Wang Minjin
Published: December 2022

Introduction

Infectious meningitis and encephalitis (ME) are life-threatening conditions are caused by various pathogens. Conventional laboratory tests with low sensitivity and specificity cannot help with early diagnosis.

Methods

A prospective study using the novel multiplex PCR detection for 18 pathogens of ME (MME-18) was conducted to investigate the clinical utilization and the epidemiology characteristics of ME in southwestern China. Patients with suspected intracranial infection were recruited between May and October 2019 at West China Hospital of Sichuan University. The MME-18 was used to detect cerebrospinal fluid, and conventional experiments including cryptococcal capsular antigen detection, GeneXpert, real-time PCR, and clinical feedback were used to verify the result of MME-18.

Results

Among 581 tested patients, 139 eligible individuals were enrolled in the study. Among them, Mycobacterium tuberculosis was the most common pathogen in mono-infection. Viruses and Cryptococcus neoformans were also frequently detected. Of 139 infected patients, 12 cases were diagnosed by MME-18 only, 57 patients by conventional testing only, and 70 cases by both comparator tests and MME-18. There were 96.3% (79/82) diagnoses made by MME-18 had a favorable outcome, and two of twelve diagnoses, made solely by MME-18, had a likely unclear clinical significance.

Discussion

The MME-18 showed satisfactory consistency with expert clinical consensus for patients presenting with ME. Combined with conventional testing and clinical suspicion, MME-18 may help clinicians with the early identification of pathogens.
Ultrasound and elastography role in pre- and post-operative evaluation of median neuropathy in patients with carpal tunnel syndrome
Authors: Wu Han , Zhao Hong-Juan , Xue Wei-Li , Wang Yi-Chun , Zhang Wu-Yue , Wang Xiao-Lei
Published: December 2022

Introduction

Carpal tunnel syndrome (CTS) is a common compression neuropathy of the median nerve in the wrist. Early diagnosis of CTS is essential for selecting treatment options and assessing prognosis. The current diagnosis of CTS is based on the patient's clinical symptoms, signs, and an electromyography (EMG) test. However, they have some limitations. Recently, ultrasound has been adopted as an adjunct diagnostic tool for electromyography (EMG). Ultrasound is a non-invasive and cost-effective technique. It provides a dynamic display of morphological changes in the median nerve and an assessment of CTS etiology such as tenosynovitis, mass compression, and tendon disease. This study aimed to investigate the value of conventional ultrasound and real-time shear wave elastography (SWE) in evaluation of median neuropathy in patients with carpal tunnel syndrome (CTS) before and after surgery.

Methods

First, the Boston Carpal Tunnel Questionnaire (BCTQ) was administered to patients with CTS. All subjects were measured at three levels: the distal 1/3 of the forearm, the carpal tunnel inlet, and the distal carpal tunnel using conventional ultrasound and SWE. Median nerve parameters were examined in patients with CTS 1 week after surgery.

Results

The cross-sectional area (CSA) and stiffness of the median nerve at the carpal tunnel inlet and distal carpal tunnel were significantly higher in patients with CTS than in healthy controls (p < 0.001). The CSA and stiffness of the median nerve at the carpal tunnel inlet were statistically significantly significantly between pre- and postoperative patients with CTS (p < 0.001). The CSA and stiffness of the nerve in patients with CTS had a positive correlation with electrophysiology severity.

Conclusions and discussion

Conventional ultrasound and elastography are valuable in the diagnosis of CTS and are useful in the clinical assessment of patient's nerve recovery after operation.
Differential diagnosis of pancreatic cystic neoplasms through a radiomics-assisted system
Authors: Dong Zhenglin , Chen Xiahan , Cheng Zhaorui , Luo Yuanbo , He Min , Chen Tao , Zhang Zijie , Qian Xiaohua , Chen Wei
Published: December 2022

Pancreatic cystic neoplasms (PCNs) are a group of heterogeneous diseases with distinct prognosis. Existing differential diagnosis methods require invasive biopsy or prolonged monitoring. We sought to develop an inexpensive, non-invasive differential diagnosis system for PCNs based on radiomics features and clinical characteristics for a higher total PCN screening rate. We retrospectively analyzed computed tomography images and clinical data from 129 patients with PCN, including 47 patients with intraductal papillary mucinous neoplasms (IPMNs), 49 patients with serous cystadenomas (SCNs), and 33 patients with mucinous cystic neoplasms (MCNs). Six clinical characteristics and 944 radiomics features were tested, and nine features were finally selected for model construction using DXScore algorithm. A five-fold cross-validation algorithm and a test group were applied to verify the results. In the five-fold cross-validation section, the AUC value of our model was 0.8687, and the total accuracy rate was 74.23%, wherein the accuracy rates of IPMNs, SCNs, and MCNs were 74.26%, 78.37%, and 68.00%, respectively. In the test group, the AUC value was 0.8462 and the total accuracy rate was 73.61%. In conclusion, our research constructed an end-to-end powerful PCN differential diagnosis system based on radiomics method, which could assist decision-making in clinical practice.
Characteristics and outcomes of pediatric testicular yolk Sac tumor
Authors: Li Maoxian , Wang Jinkui , Wang Jianyu , Zhang Deying , Hua Yi , Liu Feng , Lu Peng , Liu Junhong , Liu Xing , Lin Tao , Wei Guanghui , He Dawei
Published: December 2022

Purpose

Pediatric testicular yolk sac tumor is a rare malignant germ cell tumor and there is a lack of large clinical studies. The purpose of this study is to summarize the clinical characteristics of pediatric testicular yolk tumor and evaluate the prognostic factors.

Materials and methods

The medical records of children with testicular yolk sac tumor in one pediatric medical centre in China from January 2005 to January 2021 were retrospectively investigated. Data regarding clinical characteristics, treatment and prognosis were collected.

Results

A total of 109 patients with a median diagnosed age of 18 months (range 2–69) were included in this study; of them 100 were diagnosed as stage I, 6 as stage II and 3 as stage IV. All patients underwent radical orchiectomy, and 61 of them underwent postoperative chemotherapy. The mean follow-up time was 61.3 months (range 3–259), during that time, 8 patients experienced relapse. The five-year overall survival was 90.6% (95% CI 84.6%–96.7%). Univariate Cox regression analysis showed that disease stage, relapse, maximum tumor diameter, and alpha-fetoprotein returning to normal within 2 months postoperatively were risk factors for survival (HRs of 25.43, 26.43, 1.48 and 0.08, respectively, p < 0.05). Multivariate Cox regression analysis suggested that higher disease stage and relapse were independent adverse factors for survival (HRs of 148.30 and 94.58, respectively, p < 0.05).

Conclusions

The prognosis of pediatric testicular yolk sac tumor is generally excellent. A higher disease stage and the occurrence of relapse could predict a poor prognosis. The individualized management of children with testicular yolk sac tumor according to risk classification is feasible.
Lysophosphatidic acid suppresses apoptosis of high-grade serous ovarian cancer cells by inducing autophagy activity and promotes cell-cycle progression via EGFR-PI3K/Aurora-AThr288-geminin dual signaling pathways
Authors: Zhao Haile , Jia Peijun , Nanding Kathleen , Wu Man , Bai Xiaozhou , Morigen Morigen , Fan Lifei
Published: December 2022

Lysophosphatidic acid (LPA) and geminin are overexpressed in ovarian cancer, and increasing evidence supports their contribution to ovarian tumor development. Here, we reveal that geminin depletion induces autophagy suppression and enhances reactive oxygen species (ROS) production and apoptosis of high-grade serous ovarian cancer (HGSOC) cells. Bioinformatics analysis and pharmacological inhibition studies confirm that LPA activates geminin expression in the early S phase in HGSOC cells via the LPAR1/3/MMPs/EGFR/PI3K/mTOR pathway. Furthermore, LPA phosphorylates Aurora-A kinase on Thr288 through EGFR transactivation, and this event potentiates additional geminin stabilization. In turn, overexpressed and stabilized geminin regulates DNA replication, cell-cycle progression, and cell proliferation of HGSOC cells. Our data provide potential targets for enhancing the clinical benefit of HGSOC precision medicine.
Recent progress in DNA methyltransferase inhibitors as anticancer agents
Authors: Zhang Zhixiong , Wang Guan , Li Yuyan , Lei Dongsheng , Xiang Jin , Ouyang Liang , Wang Yanyan , Yang Jinliang
Published: December 2022

DNA methylation mediated by DNA methyltransferase is an important epigenetic process that regulates gene expression in mammals, which plays a key role in silencing certain genes, such as tumor suppressor genes, in cancer, and it has become a promising therapeutic target for cancer treatment. Similar to other epigenetic targets, DNA methyltransferase can also be modulated by chemical agents. Four agents have already been approved to treat hematological cancers. In order to promote the development of a DNA methyltransferase inhibitor as an anti-tumor agent, in the current review, we discuss the relationship between DNA methylation and tumor, the anti-tumor mechanism, the research progress and pharmacological properties of DNA methyltransferase inhibitors, and the future research trend of DNA methyltransferase inhibitors.