bluuebunny/crossref_metadata_2025 huggingface dataset:
Construction of a prognostic model based on eight ubiquitination-related genes via machine learning and potential therapeutics analysis for cervical cancer
Authors: Hao Yiping , Guy Mutangala Muloye , Liu Qingqing , Li Ruowen , Mao Zhonghao , Jiang Nan , Wang Bingyu , Cui Baoxia , Zhang Wenjing
Published: March 2023

Introduction: Ubiquitination is involved in many biological processes and its predictive value for prognosis in cervical cancer is still unclear.

Methods: To further explore the predictive value of the ubiquitination-related genes we obtained URGs from the Ubiquitin and Ubiquitin-like Conjugation Database, analyzed datasets from The Cancer Genome Atlas and Gene Expression Omnibus databases, and then selected differentially expressed ubiquitination-related genes between normal and cancer tissues. Then, DURGs significantly associated with overall survival were selected through univariate Cox regression. Machine learning was further used to select the DURGs. Then, we constructed and validated a reliable prognostic gene signature by multivariate analysis. In addition, we predicted the substrate proteins of the signature genes and did a functional analysis to further understand the molecular biology mechanisms. The study provided new guidelines for evaluating cervical cancer prognosis and also suggested new directions for drug development.

Results: By analyzing 1,390 URGs in GEO and TCGA databases, we obtained 175 DURGs. Our results showed 19 DURGs were related to prognosis. Finally, eight DURGs were identified via machine learning to construct the first ubiquitination prognostic gene signature. Patients were stratified into high-risk and low-risk groups and the prognosis was worse in the high-risk group. In addition, these gene protein levels were mostly consistent with their transcript level. According to the functional analysis of substrate proteins, the signature genes may be involved in cancer development through the transcription factor activity and the classical P53 pathway ubiquitination-related signaling pathways. Additionally, 71 small molecular compounds were identified as potential drugs.

Conclusion: We systematically studied the influence of ubiquitination-related genes on prognosis in cervical cancer, established a prognostic model through a machine learning algorithm, and verified it. Also, our study provides a new treatment strategy for cervical cancer.
Accelerated institutionalization of an adolescent sexual and reproductive health (ASRH) intervention in Tanzania: Findings from a mixed-methods evaluation
Authors: Cutherell Meghan , Bwire Juliana , Mtei Edwin , Musau Abednego , Kahabuka Catherine , Luhanga Isabellah , Julius Augustino , Kihwele Gerald
Published: March 2023

Introduction

From 2018 to 2020, Adolescents 360 (A360), aiming to increase demand for and voluntary uptake of modern contraception among adolescent girls 15–19 years, designed and scaled an intervention in Tanzania (Kuwa Mjanja) to 13 regions through project-funded expansion. In 2020, the project began to develop a strategy for its follow-on phase, focusing on program sustainability. In this process, funder priorities led to a decision to exit A360's programming in Tanzania over a 15-month exit period. A360 elected to pursue a process of expedited institutionalization of Kuwa Mjanja into government systems during this period.

Materials and methods

The institutionalization process was facilitated in 17 local government authorities in Tanzania. Quantitative and qualitative data were gathered and analyzed including time-trend analysis of routine performance data, statistical analysis of two rounds of client exit interviews, and thematic analysis of qualitative research.

Results

The sociodemographic characteristics of adolescent girls reached under government-led implementation were comparable to those reached by A360-led implementation. Intervention productivity decreased under government-led implementation but remained consistent. Adopter method mix shifted slightly toward greater long-acting and reversible contraceptive uptake under a government-led model. Factors that enabled successful institutionalization of Kuwa Mjanja included the presence of youth-supportive policies, the establishment of school clubs which provided sexual and reproductive health education, commitment of government stakeholders, and appreciation of adolescent pregnancy as a problem. Some intervention components were important for program effectiveness but proved difficult to institutionalize, primarily because of resource constraints. Lack of adolescent sexual and reproductive health (ASRH)-focused targets and indicators disincentivized Kuwa Mjanja implementation.

Discussion

There is significant potential in operationalizing user-centered ASRH models within government structures, even in a narrow time frame. A360 saw similar performance under government-led implementation and fidelity to the unique experience that the program was designed to deliver for adolescent girls. However, beginning this process earlier presents greater opportunities, as some aspects of the institutionalization process that are critical to sustained impact, for example, shifting government policy and measurement and mobilizing government resources, require heavy coordination and long-term efforts. Programs pursuing institutionalization in a shorter time frame would benefit from setting realistic expectations. This may include prioritizing a smaller subset of program components that have the greatest impact.
Aerosolized nicotine from e-cigarettes alters gene expression, increases lung protein permeability, and impairs viral clearance in murine influenza infection
Authors: Maishan Mazharul , Sarma Aartik , Chun Lauren F. , Caldera Saharai , Fang Xiaohui , Abbott Jason , Christenson Stephanie A. , Langelier Charles R. , Calfee Carolyn S. , Gotts Jeffrey E. , Matthay Michael A.
Published: March 2023

E-cigarette use has rapidly increased as an alternative means of nicotine delivery by heated aerosolization. Recent studies demonstrate nicotine-containing e-cigarette aerosols can have immunosuppressive and pro-inflammatory effects, but it remains unclear how e-cigarettes and the constituents of e-liquids may impact acute lung injury and the development of acute respiratory distress syndrome caused by viral pneumonia. Therefore, in these studies, mice were exposed one hour per day over nine consecutive days to aerosol generated by the clinically-relevant tank-style Aspire Nautilus aerosolizing e-liquid containing a mixture of vegetable glycerin and propylene glycol (VG/PG) with or without nicotine. Exposure to the nicotine-containing aerosol resulted in clinically-relevant levels of plasma cotinine, a nicotine-derived metabolite, and an increase in the pro-inflammatory cytokines IL-17A, CXCL1, and MCP-1 in the distal airspaces. Following the e-cigarette exposure, mice were intranasally inoculated with influenza A virus (H1N1 PR8 strain). Exposure to aerosols generated from VG/PG with and without nicotine caused greater influenza-induced production in the distal airspaces of the pro-inflammatory cytokines IFN-γ, TNFα, IL-1β, IL-6, IL-17A, and MCP-1 at 7 days post inoculation (dpi). Compared to the aerosolized carrier VG/PG, in mice exposed to aerosolized nicotine there was a significantly lower amount of Mucin 5 subtype AC (MUC5AC) in the distal airspaces and significantly higher lung permeability to protein and viral load in lungs at 7 dpi with influenza. Additionally, nicotine caused relative downregulation of genes associated with ciliary function and fluid clearance and an increased expression of pro-inflammatory pathways at 7 dpi. These results show that (1) the e-liquid carrier VG/PG increases the pro-inflammatory immune responses to viral pneumonia and that (2) nicotine in an e-cigarette aerosol alters the transcriptomic response to pathogens, blunts host defense mechanisms, increases lung barrier permeability, and reduces viral clearance during influenza infection. In conclusion, acute exposure to aerosolized nicotine can impair clearance of viral infection and exacerbate lung injury, findings that have implications for the regulation of e-cigarette products.
Causal associations between modifiable risk factors and pancreatitis: A comprehensive Mendelian randomization study
Authors: Mao Xiaotong , Mao Shenghan , Sun Hongxin , Huang Fuquan , Wang Yuanchen , Zhang Deyu , Wang Qiwen , Li Zhaoshen , Zou Wenbin , Liao Zhuan
Published: March 2023

Background

The pathogenesis of pancreatitis involves diverse environmental risk factors, some of which have not yet been clearly elucidated. This study systematically investigated the causal effects of genetically predicted modifiable risk factors on pancreatitis using the Mendelian randomization (MR) approach.

Methods

Genetic variants associated with 30 exposure factors were obtained from genome-wide association studies. Summary-level statistical data for acute pancreatitis (AP), chronic pancreatitis (CP), alcohol-induced AP (AAP) and alcohol-induced CP (ACP) were obtained from FinnGen consortia. Univariable and multivariable MR analyses were performed to identify causal risk factors for pancreatitis.

Results

Genetic predisposition to smoking (OR = 1.314, P = 0.021), cholelithiasis (OR = 1.365, P = 1.307E-19) and inflammatory bowel disease (IBD) (OR = 1.063, P = 0.008) as well as higher triglycerides (OR = 1.189, P = 0.016), body mass index (BMI) (OR = 1.335, P = 3.077E-04), whole body fat mass (OR = 1.291, P = 0.004) and waist circumference (OR = 1.466, P = 0.011) were associated with increased risk of AP. The effect of obesity traits on AP was attenuated after correcting for cholelithiasis. Genetically-driven smoking (OR = 1.595, P = 0.005), alcohol consumption (OR = 3.142, P = 0.020), cholelithiasis (OR = 1.180, P = 0.001), autoimmune diseases (OR = 1.123, P = 0.008), IBD (OR = 1.066, P = 0.042), type 2 diabetes (OR = 1.121, P = 0.029), and higher serum calcium (OR = 1.933, P = 0.018), triglycerides (OR = 1.222, P = 0.021) and waist-to-hip ratio (OR = 1.632, P = 0.023) increased the risk of CP. Cholelithiasis, triglycerides and the waist-to-hip ratio remained significant predictors in the multivariable MR. Genetically predicted alcohol drinking was associated with increased risk of AAP (OR = 15.045, P = 0.001) and ACP (OR = 6.042, P = 0.014). After adjustment of alcohol drinking, genetic liability to IBD had a similar significant causal effect on AAP (OR = 1.137, P = 0.049), while testosterone (OR = 0.270, P = 0.002) a triglyceride (OR = 1.610, P = 0.001) and hip circumference (OR = 0.648, P = 0.040) were significantly associated with ACP. Genetically predicted higher education and household income levels could lower the risk of pancreatitis.

Conclusions

This MR study provides evidence of complex causal associations between modifiable risk factors and pancreatitis. These findings provide new insights into potential therapeutic and prevention strategies.
ROS-AMPK/mTOR-dependent enterocyte autophagy is involved in the regulation of Giardia infection-related tight junction protein and nitric oxide levels
Authors: Wu Jingxue , Yang Yongwu , Liu Lin , Zhu Weining , Liu Min , Yu Xiran , Li Wei
Published: March 2023

Giardia duodenalis, a cosmopolitan noninvasive protozoan parasite of zoonotic concern and public health importance, infects the upper portions of the small intestine and causes one of the most common gastrointestinal diseases globally termed giardiasis, especially in situations lacking safe drinking water and adequate sanitation services. The pathogenesis of giardiasis is complex and involves multiple factors from the interaction of Giardia and intestinal epithelial cells (IECs). Autophagy is an evolutionarily conserved catabolic pathway that involves multiple pathological conditions including infection. Thus far, it remains uncertain if autophagy occurs in Giardia-infected IECs and if autophagic process is associated with the pathogenic factors of giardiasis, such as tight junction (TJ) barrier defects and nitric oxide (NO) release of IECs. Here Giardia-in vitro exposed IECs showed upregulation of a series of autophagy-related molecules, such as LC3, Beclin1, Atg7, Atg16L1, and ULK1, and downregulation of p62 protein. IEC autophagy induced by Giardia was further assessed by using autophagy flux inhibitor, chloroquine (CQ), with the ratio of LC3-II/LC3-I significantly increased and downregulated p62 significantly reversed. Inhibition of autophagy by 3-methyladenine (3-MA) rather than CQ could markedly reverse Giardia-induced downregulation of TJ proteins (claudin-1, claudin-4, occludin, and ZO-1; also known as epithelial cell markers) and NO release, implying the involvement of early-stage autophagy in TJ/NO regulation. We subsequently confirmed the role of ROS-mediated AMPK/mTOR signaling in modulating Giardia-induced autophagy, TJ protein expression, and NO release. In turn, impairment of early-stage autophagy by 3-MA and late-stage autophagy by CQ both exhibited an exacerbated effect on ROS accumulation in IECs. Collectively, we present the first attempt to link the occurrence of IEC autophagy with Giardia infection in vitro, and provides novel insights into the contribution of ROS-AMPK/mTOR-dependent autophagy to Giardia infection-related downregulation of TJ protein and NO levels.
Targeting of chimeric antigen receptor T cell metabolism to improve therapeutic outcomes
Authors: Nanjireddy Priyanka Maridhi , Olejniczak Scott H. , Buxbaum Nataliya Prokopenko
Published: March 2023

Genetically engineered chimeric antigen receptor (CAR) T cells can cure patients with cancers that are refractory to standard therapeutic approaches. To date, adoptive cell therapies have been less effective against solid tumors, largely due to impaired homing and function of immune cells within the immunosuppressive tumor microenvironment (TME). Cellular metabolism plays a key role in T cell function and survival and is amenable to manipulation. This manuscript provides an overview of known aspects of CAR T metabolism and describes potential approaches to manipulate metabolic features of CAR T to yield better anti-tumor responses. Distinct T cell phenotypes that are linked to cellular metabolism profiles are associated with improved anti-tumor responses. Several steps within the CAR T manufacture process are amenable to interventions that can generate and maintain favorable intracellular metabolism phenotypes. For example, co-stimulatory signaling is executed through metabolic rewiring. Use of metabolic regulators during CAR T expansion or systemically in the patient following adoptive transfer are described as potential approaches to generate and maintain metabolic states that can confer improved in vivo T cell function and persistence. Cytokine and nutrient selection during the expansion process can be tailored to yield CAR T products with more favorable metabolic features. In summary, improved understanding of CAR T cellular metabolism and its manipulations have the potential to guide the development of more effective adoptive cell therapies.
Cyclophosphamide-induced seizures in a patient with neuropsychiatric systemic lupus erythematosus (NPSLE): A case report
Authors: Zhang Lingshu , Shi Ying , Zhang Jingyao , Wu Jing , Jiang Wei
Published: March 2023

Seizures are life-threatening complications of neuropsychiatric systemic lupus erythematosus (NPSLE) and are often associated with poor outcomes. Cyclophosphamide immunotherapy is the mainstay of NPSLE treatment. We report the unique case of a patient with NPSLE who developed seizures soon after her first and second doses of low-dose cyclophosphamide. The exact pathophysiological mechanism underlying cyclophosphamide-induced seizures is not well understood. However, this unusual drug-associated side effect of cyclophosphamide is thought to be due to the drug’s unique pharmacology. Clinicians should be aware of this complication to make a correct diagnosis and adjust the immunosuppressive regimens very carefully.
Transmission of stimulus-induced epigenetic changes through cell division is coupled to continuous transcription factor activity
Authors: Sun Sarah , Aguirre-Gamboa Raúl , Barreiro Luis B.
Published: March 2023

Trained immunity, or innate immune memory, has been attributed to the long-term retention of stimulus-induced histone post-translational modifications (PTMs) following clearance of the initial stimulus. Yet, it remains unknown how this epigenetic memory can persist for months in dividing cells given the lack of any known mechanism for stimulus-induced histone PTMs to be directly copied from parent to daughter strand during DNA replication. Here, using time course RNA-seq, ChIP-seq, and infection assays, we find that trained macrophages are transcriptionally, epigenetically, and functionally re-programmed for at least 14 cell divisions after stimulus washout. However, the epigenetic changes observed after multiple rounds of cell division do not result from the self-sustained propagation of stimulus-induced epigenetic changes through cell division. Instead, long-lasting epigenetic differences between trained and non-trained cells are always coupled with changes in transcription factor (TF) activity, emphasizing the central role played by TFs, and gene expression changes more broadly, in driving the transmission of stimulus-induced epigenetic changes across cell divisions.
Bioengineered bacterial outer membrane vesicles encapsulated Polybia–mastoparan I fusion peptide as a promising nanoplatform for bladder cancer immune-modulatory chemotherapy
Authors: Ren Chunyu , Li Yangyang , Cong Zhaoqing , Li Zhuoran , Xie Leiming , Wu Song
Published: March 2023

Background

Nanosized bacterial outer membrane vesicles (OMVs) secreted by Gram-negative bacteria have emerged as a novel antitumor nanomedicine reagent due to their immunostimulatory properties. The encapsulated bacterial composition in OMVs can be edited via manipulating bioengineering technology on paternal bacteria, allowing us to design an ingenious antitumor platform by loading the Polybia–mastoparan I (MPI) fusion peptide into OMVs.

Methods

OMVs containing the MPI fusion peptide were obtained from bioengineered Escherichia coli transformed with recombinant plasmid. The antitumor efficacy of bioengineered OMVs in vitro was verified by performing cell viability and wound-healing and apoptosis assays using MB49 and UMUC3 cells, respectively. Subcutaneous MB49 tumor-bearing mice were involved to investigate the tumor inhibition ability of bioengineered OMVs. Moreover, the activated immune response in tumor and the biosafety were also evaluated in detail.

Results

The resulting OMVs had the successful encapsulation of MPI fusion peptides and were subjected to physical characterization for morphology, size, and zeta potential. Cell viabilities of bladder cancer cells including MB49 and UMUC3 rather than a non-carcinomatous cell line (bEnd.3) were decreased when incubated with bioengineered OMVs. In addition, bioengineered OMVs restrained migration and induced apoptosis of bladder cancer cells. With intratumor injection of bioengineered OMVs, growths of subcutaneous MB49 tumors were significantly restricted. The inherent immunostimulation of OMVs was demonstrated to trigger maturation of dendritic cells (DCs), recruitment of macrophages, and infiltration of cytotoxic T lymphocytes (CTLs), resulting in the increased secretion of pro-inflammatory cytokines (IL-6, TNF-α, and IFN-γ). Meanwhile, several lines of evidence also indicated that bioengineered OMVs had satisfactory biosafety.

Conclusion

Bioengineered OMVs fabricated in the present study were characterized by strong bladder cancer suppression and great biocompatibility, providing a new avenue for clinical bladder cancer therapy.
Adenosine deaminase augments SARS-CoV-2 specific cellular and humoral responses in aged mouse models of immunization and challenge
Authors: Gary Ebony N. , Tursi Nicholas J. , Warner Bryce M. , Cuismano Gina , Connors Jennifer , Parzych Elizabeth M. , Griffin Bryan D. , Bell Matthew R. , Ali Ali R. , Frase Drew , Hojecki Casey E. , Canziani Gabriela A. , Chaiken Irwin , Kannan Toshitha , Moffat Estella , Embury-Hyatt Carissa , Wooton Sarah K. , Kossenkov Andrew , Patel Ami , Kobasa Darwyn , Kutzler Michele A. , Haddad Elias K. , Weiner David B.
Published: March 2023

Despite numerous clinically available vaccines and therapeutics, aged patients remain at increased risk for COVID-19 morbidity. Furthermore, various patient populations, including the aged can have suboptimal responses to SARS-CoV-2 vaccine antigens. Here, we characterized vaccine-induced responses to SARS-CoV-2 synthetic DNA vaccine antigens in aged mice. Aged mice exhibited altered cellular responses, including decreased IFNγ secretion and increased TNFα and IL-4 secretion suggestive of TH2-skewed responses. Aged mice exhibited decreased total binding and neutralizing antibodies in their serum but significantly increased TH2-type antigen-specific IgG1 antibody compared to their young counterparts. Strategies to enhance vaccine-induced immune responses are important, especially in aged patient populations. We observed that co-immunization with plasmid-encoded adenosine deaminase (pADA)enhanced immune responses in young animals. Ageing is associated with decreases in ADA function and expression. Here, we report that co-immunization with pADA enhanced IFNγ secretion while decreasing TNFα and IL-4 secretion. pADA expanded the breadth and affinity SARS-CoV-2 spike-specific antibodies while supporting TH1-type humoral responses in aged mice. scRNAseq analysis of aged lymph nodes revealed that pADA co-immunization supported a TH1 gene profile and decreased FoxP3 gene expression. Upon challenge, pADA co-immunization decreased viral loads in aged mice. These data support the use of mice as a model for age-associated decreased vaccine immunogenicity and infection-mediated morbidity and mortality in the context of SARS-CoV-2 vaccines and provide support for the use of adenosine deaminase as a molecular adjuvant in immune-challenged populations.
Low-dose administration of prednisone has a good effect on the treatment of prolonged hematologic toxicity post-CD19 CAR-T cell therapy
Authors: Wang Jiaxi , Zhang Meng , Lyu Hairong , Guo Ruiting , Xiao Xia , Bai Xue , Pu Yedi , Meng Juanxia , Li Qing , Yuan Ting , Lu Wenyi , Zhao Mingfeng
Published: March 2023

Introduction

Hematologic toxicity (HT) is a joint adverse event after CAR-T cells infusion. Some patients experience prolonged hematologic toxicity (PHT), which is challenging to treat.

Methods

We collected clinical data from patients with relapsed refractory B-ALL treated with CD19 CAR-T cells. Patients with PHT who did not respond to erythropoietin, platelet receptor agonists, transfusion, or G-CSF and eventually received low-dose prednisone therapy were included in the analysis. We retrospectively analyzed the efficacy and safety of low-dose prednisone on PHT.

Results

Among 109 patients treated with CD19 CAR-T cells, 78.9% (86/109) of patients were evaluated as PHT. Of these, 15 patients had persistent hematological toxicity after infusion (12 were grade 3/4 cytopenia, 12 were trilineage cytopenia and 3 were bilineage cytopenia), 2 developed cytopenia without apparent cause after D28. The initial prednisone dose was 0.5 mg/kg/day, and the median response time was 21 days (7-40 days). The recovery rate of blood count was 100%, and the complete recovery rate ranged from 60% to 66.67%. Especially exciting was that HT recurred in 6 patients after stopping prednisone. They were relieved again after the administration of prednisone. The median follow-up time was 14.97 months (4.1-31.2 months). Twelve-month duration of PFS and OS rates were 58.8% (±11.9%) and 64.7% (±11.6%). We did not observe any other side effects of prednisone apart from drug-controllable hyperglycemia and hypertension.

Discussion

We suggest that low-dose prednisone is a beneficial and tolerable therapy for PHT after CAR-T cells. The trials have been registered at www.chictr.org.cn as ChiCTR-ONN-16009862 (November 14, 2016) and ChiCTR1800015164 (March 11, 2018).
Breast milk microRNAs: Potential players in oral tolerance development
Authors: Ahlberg Emelie , Al-Kaabawi Ahmed , Thune Rebecka , Simpson Melanie Rae , Pedersen Sindre Andre , Cione Erika , Jenmalm Maria Christina , Tingö Lina
Published: March 2023

Breast milk is an essential source of nutrition and hydration for the infant. In addition, this highly complex biological fluid contains numerous immunologically active factors such as microorganisms, immunoglobulins, cytokines and microRNAs (miRNAs). Here, we set out to predict the function of the top 10 expressed miRNAs in human breast milk, focusing on their relevance in oral tolerance development and allergy prevention in the infant. The top expressed miRNAs in human breast milk were identified on basis of previous peer-reviewed studies gathered from a recent systematic review and an updated literature search. The miRNAs with the highest expression levels in each study were used to identify the 10 most common miRNAs or miRNA families across studies and these were selected for subsequent target prediction. The predictions were performed using TargetScan in combination with the Database for Annotation, Visualization and Integrated Discovery. The ten top expressed miRNAs were: let-7-5p family, miR-148a-3p, miR-30-5p family, miR-200a-3p + miR-141-3p, miR-22-3p, miR-181-5p family, miR-146b-5p, miR-378a-3p, miR-29-3p family, miR-200b/c-3p and miR-429-3p. The target prediction identified 3,588 potential target genes and 127 Kyoto Encyclopedia of Genes and Genomes pathways; several connected to the immune system, including TGF-b and T cell receptor signaling and T-helper cell differentiation. This review highlights the role of breast milk miRNAs and their potential contribution to infant immune maturation. Indeed, breast milk miRNAs seem to be involved in several pathways that influence oral tolerance development.
Ecological adaptation in cod and herring and possible consequences of future climate change in the Baltic Sea
Authors: Andersson Leif , André Carl , Johannesson Kerstin , Pettersson Mats
Published: March 2023

The Atlantic herring and Atlantic cod are two marine fish species that have successfully adapted to the brackish Baltic Sea, and the former is able to spawn in near-freshwater conditions in the inner Gulf of Bothnia. Here, we review the state of current knowledge concerning ecological adaptation in the two species and make an attempt to predict how they will be able to cope with future climate change. Previous whole genome sequencing studies in Atlantic herring have revealed hundreds of genetic loci underlying ecological adaptation, including several loci that show very strong associations to variation in salinity and temperature. These results suggest the existence of standing genetic variation available for adaptation to a changing environment. However, although Atlantic herring probably has the genetic potential to adapt, its future status also depends on how climate change will affect plankton production and competing species, such as sprat and three-spined stickleback. In cod, the situation is challenging, as there is only one true Baltic population, spawning east of Bornholm and then dispersing towards the east and north. This Baltic cod population is threatened by overfishing, low oxygen levels in benthic waters and generally bad physiological condition of individual fish, in addition to being completely isolated from gene flow from nearby cod populations at the entrance of the Baltic Sea.
Predicting the impacts of climate change on the distribution of European syngnathids over the next century
Authors: Monteiro Nuno , Pinheiro Sara , Magalhães Susana , Tarroso Pedro , Vincent Amanda
Published: March 2023

At the latitudinal interval that encompasses Europe, due to the gradual seawater warming imposed by climate change, there is now continuing evidence for a widespread pattern of poleward range shifts, often translated by expansions in the northern leading edges of distribution and contraction episodes at the southern boundaries. As the distribution of biodiversity is far from static, it seems imperative that we can predict changes in species’ geographic ranges to potentially circumvent severe biodiversity losses in the near future. Here, we focus on syngnathids, flagship species and umbrella taxa for coastal marine ecosystems, and attempt to identify areas of environmental suitability in Europe over the next century, according to distinct greenhouse gas concentration trajectories. Our results seamlessly match the general and region-specific impacts of climate change projections for European seas. Especially within the Atlantic Coast, species are expected to continue poleward range shifts, with the hotspot of syngnathid diversity remaining around the Celtic-Biscay Shelf, albeit with slightly distinct species composition from that of present day. The most dramatic changes are expected within semi-enclosed areas such as the Baltic, the Mediterranean and the Black Sea, where present-day endemic species diversity is likely to plunge, especially under a ‘business-as-usual’ scenario. When looking at the potential protective role of ‘no-take’ marine protected areas (MPAs) on European syngnathids, a clear latitudinal asymmetry emerged. From the Atlantic diversity hotspot downwards, and especially in the Mediterranean and Black Sea, the current ‘no-take’ MPA layout, if it remains static, will not be especially effective in either safeguarding syngnathid diversity or delaying the expected gradual species disappearance. Europe needs to be prepared to implement, at a continental scale, coordinated conservation measures aimed at preventing (or delaying, at the very least) the loss of its marine endemic species. As umbrella species, conservation efforts aimed at syngnathids will surely have a positive impact on coastal ecosystems.
Epidemiology of turbot bacterial diseases in China between October 2016 and December 2019
Authors: Gao Ye , Wang Qiyao , Liu Yaokuan , Ma Yue , Jin Huaiyuan , Liu Jingjing , Wang Huilin , Yan Yongwei , Li Jie
Published: March 2023

Turbot (Scophthalmus maximus) is an important commercial fish in China that can be infected by a series of bacterial pathogens, leading to great economic losses. In this study we focused on the epidemiology of turbot bacterial diseases in the major farming areas in China for three years. A total of 155 cases with 446 diseased turbots were investigated, and dominant bacterial pathogens were isolated from 137 cases (344 turbots). Thus, bacteria are the major threat to farming turbot in China. Edwardsiella piscicida was the major pathogen, which isolated as the dominant colony in 62 cases (40.00%) with 151 turbots (33.85%). Aeromonas salmonicida was isolated in 57 cases (36.77%) with 116 turbots (26.01%). Vibrio anguillarum was isolated in nine cases (5.81%), and Streptococcus parauberis in five cases (3.23%). Photobacterium damselae and Mycobacterium marinum were also isolated from one or two diseased fish. Other Vibrio spp. were isolated in 15 cases (9.68%). Two species of pathogen were isolated in 13 cases, and three species (E. piscicida, A. salmonicida, and S. parauberis) in one case. In 19 cases, no bacteria were isolated. Based on the annual disease analysis, we found that the E. piscicida infection proportion of total cases was greatly decreased, which may be caused by the attenuated vaccine inoculated in 2018. The antibiotic resistance of E. piscicida strains isolated in Weifang city was also determined. We found that the resistance to ceftriaxone, doxycycline, and SMZ/TMP were significantly increased from October 2016 to June 2018, and all the E. piscicida isolates exhibited resistance to SMZ/TMP in June 2018. These results indicated that E. piscicida is the major threat to turbot farming in China, and the attenuated E. piscicida vaccine exhibits effective protection. The usage of antibiotics may induce resistance quickly. Thus, development of vaccines is an important work for sustainable development of turbot farming in the future.
AIDS with obesity, hypothyroidism and elevated serum creatinine: A case report
Authors: Zhang Chenxi , Qian Chuyue , Wang Wanning , Chen Zhi , Lin Yangyang , Sun Mindan
Published: March 2023

Hypothyroidism is a prevalent endocrine illness with a variety of clinical symptoms, but among which elevated serum creatinine is uncommon. Hypothyroidism is also common in acquired immunodeficiency syndrome (AIDS) patients, especially those receiving highly active antiretroviral treatment (HAART). Here we present a case of a young AIDS patient with hypothyroidism, increased serum creatinine, and obesity. Despite the lack of a kidney biopsy, following levothyroxine (LT4) therapy, his serum creatinine recovered to normal levels, and weight loss, edema, weakness, rough skin and other clinical symptoms obtained notable improvement. This highlights the need of clinicians paying attention to whether thyroid function is aberrant in human immunodeficiency virus (HIV) patients with increased creatinine, edema and significant weight gain since prompt thyroid hormone therapy can restore the alterations in renal function and avoid invasive renal biopsy.
Considerations for the use of immunosuppression for the management of pemphigus during the COVID-19 pandemic with a focus on rituximab: Case reports from a single center experience in Australia
Authors: Koszegi Ben , Stone Corey , Murrell Dedee F.
Published: March 2023

Pemphigus is a rare group of autoimmune mucocutaneous blistering conditions for which the mainstay of treatment is immunosuppression. This is usually achieved with high dose corticosteroids as well as steroid sparing agents. Rituximab is now recommended as a first line treatment for moderate to severe pemphigus vulgaris, the commonest form of pemphigus, alongside corticosteroids. During the early stages of the COVID-19 pandemic the use of rituximab was reduced in our department due to its long term irreversible B-cell suppression. During the COVID-19 pandemic careful pharmacological selection was undertaken for our pemphigus patients to balance the risks of immunosuppression. To demonstrate this, we report three pemphigus patients who required treatment for COVID-19 and assessment throughout the pandemic. To date there has been limited published data regarding the clinical outcomes of pemphigus patients who have developed COVID-19 infections following rituximab infusions, especially in those patients who have received COVID-19 vaccinations. Following careful personalized consideration, all three pemphigus patients presented received rituximab infusions since the start of the COVID-19 pandemic. These patients had also received COVID-19 vaccinations prior to becoming infected with COVID-19. Each patient had a mild COVID-19 infection after receiving rituximab. We advocate for all pemphigus patients to have a full course of COVID-19 vaccinations. Antibody response to COVID-19 vaccinations should ideally be confirmed by measuring pemphigus patient’s SARS-CoV-2 antibodies prior to receiving rituximab.
Warm needle acupuncture for osteoarthritis: An overview of systematic reviews and meta-analysis
Authors: Jun Ji Hee , Choi Tae-Young , Park Sunju , Lee Myeong Soo
Published: March 2023

Background

Osteoarthritis (OA) is a chronic disease that is a major cause of pain and functional disability. Warm needle acupuncture (WA) therapy has been widely used to treat OA. This overview summarizes the evidence from systematic reviews (SRs) and assesses the methodological quality of previous SRs that evaluated the use of WA therapy for OA.

Methods

We searched electronic databases to identify SRs that evaluated the efficacy of WA therapy for OA. Two reviewers independently extracted data and assessed the methodological quality of the reviews according to the A Measurement Tool to Assess Systematic Reviews (AMSTAR 2) tool. The reporting quality was assessed using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis 2020 (PRISMA 2020) guidelines. The quality of evidence was assessed according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach.

Results

Fifteen SRs were included in this study. WA therapy was more effective than control conditions for the treatment of OA. The results of the AMSTAR 2 tool showed that the methodological quality of all included studies was critically low. The items with the lowest scores were item 2 (reporting the protocol), item 7 (listing excluded studies and justifying the exclusions), and item 16 (including conflicts of interest). Regarding the PRISMA guidelines, 2 SRs exhibited greater than 85% compliance. The overall quality of evidence in the included SRs ranged from “very low” to “moderate.”

Conclusion

This overview shows that WA therapy was more effective than the control treatment for OA. However, the methodological quality of the reviews was low, indicating the need for improvements in the collection of evidence. Future studies are needed to collect high-quality evidence regarding the use of WA for OA.

Systematic review registration

https://www.researchregistry.com/, Research Registry (reviewregistry1317).
Prognostic performance of the REDS score, SOFA score, NEWS2 score, and the red-flag, NICE high-risk, and SIRS criteria to predict survival at 180 days, in emergency department patients admitted with suspected sepsis – An observational cohort study
Authors: Sivayoham Narani , Hussain Adil N. , Sheerin Thomas , Dwivedi Prerak , Curpanen Danalakshmee , Rhodes Andrew
Published: March 2023

Background

Patients admitted to hospital with sepsis are at persistent risk of poor outcome after discharge. Many tools are available to risk-stratify sepsis patients for in-hospital mortality. This study aimed to identify the best risk-stratification tool to prognosticate outcome 180 days after admission via the emergency department (ED) with suspected sepsis.

Methods

A retrospective observational cohort study was performed of adult ED patients who were admitted after receiving intravenous antibiotics for the treatment of a suspected sepsis, between 1st March and 31st August 2019. The Risk-stratification of ED suspected Sepsis (REDS) score, SOFA score, Red-flag sepsis criteria met, NICE high-risk criteria met, the NEWS2 score and the SIRS criteria, were calculated for each patient. Death and survival at 180 days were noted. Patients were stratified in to high and low-risk groups as per accepted criteria for each risk-stratification tool. Kaplan–Meier curves were plotted for each tool and the log-rank test performed. The tools were compared using Cox-proportional hazard regression (CPHR). The tools were studied further in those without the following specified co-morbidities: Dementia, malignancy, Rockwood Frailty score of 6 or more, long-term oxygen therapy and previous do-not-resuscitate orders.

Results

Of the 1,057 patients studied 146 (13.8%) died at hospital discharge and 284 were known to have died within 180 days. Overall survival proportion was 74.4% at 180 days and 8.6% of the population was censored before 180 days. Only the REDS and SOFA scores identified less than 50% of the population as high-risk. All tools except the SIRS criteria, prognosticated for outcome at 180 days; Log-rank tests between high and low-risk groups were: REDS score p < 0.0001, SOFA score p < 0.0001, Red-flag criteria p = 0.001, NICE high-risk criteria p = 0.0001, NEWS2 score p = 0.003 and SIRS criteria p = 0.98. On CPHR, the REDS [Hazard ratio (HR) 2.54 (1.92–3.35)] and SOFA [HR 1.58 (1.24–2.03)] scores out-performed the other risk-stratification tools. In patients without the specified co-morbidities, only the REDS score and the SOFA score risk-stratified for outcome at 180 days.

Conclusion

In this study, all the risk-stratification tools studied were found to prognosticate for outcome at 180 days, except the SIRS criteria. The REDS and SOFA scores outperformed the other tools.
The tropical cookbook: Termite diet and phylogenetics—Over geographical origin—Drive the microbiome and functional genetic structure of nests
Authors: González Plaza Juan José , Hradecký Jaromír
Published: March 2023

Termites are key decomposers of dead plant material involved in the organic matter recycling process in warm terrestrial ecosystems. Due to their prominent role as urban pests of timber, research efforts have been directed toward biocontrol strategies aimed to use pathogens in their nest. However, one of the most fascinating aspects of termites is their defense strategies that prevent the growth of detrimental microbiological strains in their nests. One of the controlling factors is the nest allied microbiome. Understanding how allied microbial strains protect termites from pathogen load could provide us with an enhanced repertoire for fighting antimicrobial-resistant strains or mining for genes for bioremediation purposes. However, a necessary first step is to characterize these microbial communities. To gain a deeper understanding of the termite nest microbiome, we used a multi-omics approach for dissecting the nest microbiome in a wide range of termite species. These cover several feeding habits and three geographical locations on two tropical sides of the Atlantic Ocean known to host hyper-diverse communities. Our experimental approach included untargeted volatile metabolomics, targeted evaluation of volatile naphthalene, a taxonomical profile for bacteria and fungi through amplicon sequencing, and further diving into the genetic repertoire through a metagenomic sequencing approach. Naphthalene was present in species belonging to the genera Nasutitermes and Cubitermes. We investigated the apparent differences in terms of bacterial community structure and discovered that feeding habits and phylogenetic relatedness had a greater influence than geographical location. The phylogenetic relatedness among nests' hosts influences primarily bacterial communities, while diet influences fungi. Finally, our metagenomic analysis revealed that the gene content provided both soil-feeding genera with similar functional profiles, while the wood-feeding genus showed a different one. Our results indicate that the nest functional profile is largely influenced by diet and phylogenetic relatedness, irrespective of geographical location.
Trophic diversification and parasitic invasion as ecological niche modulators for gut microbiota of whitefish
Authors: Kashinskaya Elena N. , Simonov Evgeniy P. , Poddubnaya Larisa G. , Vlasenko Pavel G. , Shokurova Anastasiya V. , Parshukov Aleksey N. , Andree Karl B. , Solovyev Mikhail M.
Published: March 2023

Introduction

The impact of parasites on gut microbiota of the host is well documented, but the role of the relationship between the parasite and the host in the formation of the microbiota is poorly understood. This study has focused on the influence that trophic behavior and resulting parasitism has on the structure of the microbiome.

Methods

Using 16S amplicon sequencing and newly developed methodological approaches, we characterize the gut microbiota of the sympatric pair of whitefish Coregonus lavaretus complex and the associated microbiota of cestodes parasitizing their intestine. The essence of the proposed approaches is, firstly, to use the method of successive washes of the microbiota from the cestode’s surfaces to analyze the degree of bacterial association to the tegument of the parasite. Secondly, to use a method combining the sampling of intestinal content and mucosa with the washout procedure from the mucosa to understand the real structure of the fish gut microbiota.

Results and discussion

Our results demonstrate that additional microbial community in the intestine are formed by the parasitic helminths that caused the restructuring of the microbiota in infected fish compared to those uninfected. Using the desorption method in Ringer’s solution, we have demonstrated that Proteocephalus sp. cestodes possess their own microbial community which is put together from “surface” bacteria, and bacteria which are weakly and strongly associated with the tegument, bacteria obtained after treatment of the tegument with detergent, and bacteria obtained after removal of the tegument from the cestodes.
Effects of supplementation of Bacillus amyloliquefaciens on performance, systemic immunity, and intestinal microbiota of weaned pigs experimentally infected with a pathogenic enterotoxigenic E. coli F18
Authors: Jinno Cynthia , Wong Braden , Klünemann Martina , Htoo John , Li Xunde , Liu Yanhong
Published: March 2023

The objective of this study was to investigate the effects of dietary supplementation of Bacillus (B.) amyloliquefaciens on growth performance, diarrhea, systemic immunity, and intestinal microbiota of weaned pigs experimentally infected with F18 enterotoxigenic Escherichia coli (ETEC). A total of 50 weaned pigs (7.41 ± 1.35 kg BW) were individually housed and randomly allotted to one of the following five treatments: sham control (CON-), sham B. amyloliquefaciens (BAM-), challenged control (CON+), challenged B. amyloliquefaciens (BAM+), and challenged carbadox (AGP+). The experiment lasted 28 days, with 7 days of adaptation and 21 days after the first ETEC inoculation. ETEC challenge reduced (P < 0.05) average daily gain (ADG) of pigs. Compared with CON+, AGP+ enhanced (P < 0.05) ADG, while B. amyloliquefaciens supplementation tended (P < 0.10) to increase ADG in pigs from days 0 to 21 post-inoculation (PI). The ETEC challenge increased (P < 0.05) white blood cell (WBC) count on days 7 and 21 PI, while BAM+ pigs tended (P < 0.10) to have low WBC on day 7 PI and had lower (P < 0.05) WBC on day 21 PI compared with CON+. In comparison to AGP+ fecal microbiota, BAM+ had a lower (P < 0.05) relative abundance of Lachnospiraceae on day 0 and Clostridiaceae on day 21 PI, but a higher (P < 0.05) relative abundance of Enterobacyeriaceae on day 0. In ileal digesta, the Shannon index was higher (P < 0.05) in BAM+ than in AGP+. Bray-Curtis PCoA displayed a difference in bacterial community composition in ileal digesta collected from sham pigs vs. ETEC-infected pigs on day 21 PI. Pigs in BAM+ had a greater (P < 0.05) relative abundance of Firmicutes, but a lower (P < 0.05) relative abundance of Actinomycetota and Bacteroidota in ileal digesta than pigs in AGP+. Ileal digesta from AGP+ had a greater (P < 0.05) abundance of Clostridium sensu stricto 1 but lower (P < 0.05) Bifidobacterium than pigs in BAM+. In conclusion, supplementation of B. amyloliquefaciens tended to increase ADG and had limited effects on the diarrhea of ETEC-infected pigs. However, pigs fed with B. amyloliquefaciens exhibit milder systemic inflammation than controls. B. amyloliquefaciens differently modified the intestinal microbiota of weaned pigs compared with carbadox.
A fast, sensitive and fluorescent LPMO activity assay
Authors: Ipsen Johan Ø. , Johansen Katja S. , Brander Søren
Published: March 2023

Lytic polysaccharide monooxygenases (LPMOs) are industrially relevant enzymes that utilize a copper co-factor and an oxygen species to break down recalcitrant polysaccharides. These enzymes are secreted by microorganisms and are used in lignocellulosic refineries. As such, they are interesting from both the ecological/biological and industrial perspectives. Here we describe the development of a new fluorescence-based kinetic LPMO activity assay. The assay is based on the enzymatic production of fluorescein from its reduced counterpart. The assay can detect as little as 1 nM LPMO with optimized assay conditions. Furthermore, the reduced fluorescein substrate can also be used to identify peroxidase activity as seen by the formation of fluorescein by horseradish peroxidase. The assay was shown to work well at relatively low H2O2 and dehydroascorbate concentrations. The applicability of the assay was demonstrated.