bluuebunny/crossref_metadata_2025 huggingface dataset:
Ethnicity-based classifications and medical genetics: One Health approaches from a Western Pacific perspective
Authors: Edinur Hisham A. , Mat-Ghani Siti Nor A. , Chambers Geoffrey K.
Published: September 2022

A new era presently dawns for medical genetics featuring individualised whole genome sequencing and promising personalised medical genetics. Accordingly, we direct readers attention to the continuing value of allele frequency data from Genome-Wide Association Surveys (GWAS) and single gene surveys in well-defined ethnic populations as a guide for best practice in diagnosis, therapy, and prescription. Supporting evidence is drawn from our experiences working with Austronesian volunteer subjects across the Western Pacific. In general, these studies show that their gene pool has been shaped by natural selection and become highly diverged from those of Europeans and Asians. These uniquely evolved patterns of genetic variation underlie contrasting schedules of disease incidence and drug response. Thus, recognition of historical bonds of kinship among Austronesian population groups across the Asia Pacific has distinct public health advantages from a One Health perspective. Other than diseases that are common among them like gout and diabetes, Austronesian populations face a wide range of climate-dependent infectious diseases including vector-borne pathogens as they are now scattered across the Pacific and Indian Oceans. However, we caution that the value of genetic survey data in Austronesians (and other groups too) is critically dependent on the accuracy of attached descriptive information in associated metadata, including ethnicity and admixture.
Construction and validation of BRAF mutation diagnostic model based on ultrasound examination and clinical features of patients with thyroid nodules
Authors: Xu Chan , Fang Jianqiang , Li Wanying , Sun Chenyu , Li Yaru , Lowe Scott , Bentley Rachel , Chen Shuya , He Cunyu , Li Xinxin , Wang Bing , Yin Chengliang , Li Wenxian , Li Wenle
Published: September 2022

Introduction: Fine Needle Aspiration (FNA) is currently the most popular method for identifying benign and malignant thyroid nodules. However, its diagnostic sensitivity is sometimes limited, which makes it necessary to apply genetic testing and other modalities as a secondary diagnostic method. The diagnostic accuracy of thyroid nodule can be improved by combining mutations in the B-Raf proto-oncogene serine/threonine kinase (BRAF) with FNA. Thus, this study was conducted to create a nomogram diagnostic model based on the clinical and ultrasonic characteristics of patients with BRAF mutations to aid in the identification of benign and malignant thyroid nodules using FNA.

Methods: From April 2018 to December 2021, 275 patients with thyroid nodules who underwent ultrasonography and BRAF gene testing (137 positive and 138 negative) were included from Xianyang Central Hospital. The clinical and ultrasonic characteristics of the patients were used to develop a nomographic, diagnostic model of BRAF gene mutation, and to validate and evaluate the usefulness of the model.

Results: Independent risk factors for BRAF mutations included: focal strong echogenicity (microcalcifications, OR = 3.04, 95%CI = 1.41–6.58, p = 0.005), hypoechogenicity (OR = 3.8, 95%CI = 1.14–12.61, p = 0.029), lymph node metastases (OR = 3.54, 95%CI = 1.43–8.75, p = 0.006), margin (lobulated, OR = 3.7, 95%CI = 1.66–8.23, p = 0.001; extrathyroidal invasion, OR = 2.81, 95%CI = 1.11–7.06, p = 0.029), and shape (vertical position, OR = 2.7, 95%CI = 1.11–6.59, p = 0.029). The area under the curve (AUC) of the receiver operating characteristic (ROC) curve of the BRAF mutation diagnostic model constructed on these factors was 0.806 (95% CI = 0.754–0.851), and 39.5% was set as the threshold probability of making a clinical decision. The results of the validation and clinical utility evaluation showed that our model had good predictive performance and clinical application value.

Conclusion: Our nomogram diagnostic model based on clinical and ultrasound features of patients accurately predicted the possibility of BRAF gene mutations in patients with thyroid nodules.
A role for whey acidic protein four-disulfide-core 12 (WFDC12) in the pathogenesis and development of psoriasis disease
Authors: Zhao Fulei , Zhang Chen , Li Guolin , Zheng Huaping , Gu Linna , Zhou Hong , Xiao Yuanyuan , Wang Zhen , Yu Jiadong , Hu Yawen , Zeng Fanlian , Wang Xiaoyan , Zhao Qixiang , Hu Jing , Yue Chengcheng , Zhou Pei , Huang Nongyu , Hao Yan , Wu Wenling , Cui Kaijun , Li Wei , Li Jiong
Published: September 2022

Whey acidic protein four-disulfide core domain protein 12 (WFDC12) has been implicated in the pathogenesis of psoriasis but the specific molecular mechanism is not clearly defined. In this study, we found the expression of WFDC12 protein closely correlated with psoriasis. WFDC12 in keratinocyte might increase infiltration of Langerhans cells (LCs) and monocyte-derived dendritic cells (moDDCs), up-regulating the co-stimulation molecular CD40/CD86. Th1 cells in lymph nodes were higher in K14-WFDC12 transgenic psoiasis-like mice. Meanwhile, the mRNA of IL-12 and IFN-γ in the lesion skin was significantly increased in transgenic mice. Moreover, we found that the expression of the proteins that participated in the retinoic acid–related pathway and immune signaling pathway was more changed in the lesion skin of K14-WFDC12 transgenic psoriasis-like mice. Collectively, the results implied that WFDC12 might affect the activation of the retinoic acid signaling pathway and regulate the infiltration of DC cells in the skin lesions and lymph nodes, thereby inducing Th1 cells differentiation and increasing the secretion of IFN-γ to exacerbate psoriasis in mice.
Perspective on direction of control: Cellular metabolism and macrophage polarization
Authors: Thibaut Ronan , Orliaguet Lucie , Ejlalmanesh Tina , Venteclef Nicolas , Alzaid Fawaz
Published: September 2022

Macrophages are innate immune cells with high phenotypic plasticity. Depending on the microenvironmental cues they receive, they polarize on a spectrum with extremes being pro- or anti-inflammatory. As well as responses to microenvironmental cues, cellular metabolism is increasingly recognized as a key factor influencing macrophage function. While pro-inflammatory macrophages mostly use glycolysis to meet their energetic needs, anti-inflammatory macrophages heavily rely on mitochondrial respiration. The relationship between macrophage phenotype and macrophage metabolism is well established, however its precise directionality is still under question. Indeed, whether cellular metabolism per se influences macrophage phenotype or whether macrophage polarization dictates metabolic activity is an area of active research. In this short perspective article, we sought to shed light on this area. By modulating several metabolic pathways in bone marrow-derived macrophages, we show that disruption of cellular metabolism does per se influence cytokine secretion profile and expression of key inflammatory genes. Only some pathways seem to be involved in these processes, highlighting the need for specific metabolic functions in the regulation of macrophage phenotype. We thus demonstrate that the intact nature of cellular metabolism influences macrophage phenotype and function, addressing the directionality between these two aspects of macrophage biology.
Non-coding RNA-mediated high expression of SFXN3 as a prognostic biomarker associated with paclitaxel resistance and immunosuppressive microenvironment in head and neck cancer
Authors: Chen Kailin , Gong Sha , Fang Xueliang , Li Qian , Ye Mingliang , Li Junyan , Huang Shengyan , Zhao Yuheng , Liu Na , Li Yingqin , Ma Jun
Published: September 2022

Chemoresistance is the leading cause of poor prognosis in head and neck squamous cell carcinoma (HNSC); however, promising biomarkers to identify patients for stratified chemotherapy are lacking. Sideroflexin 3 (SFXN3) is an important mitochondrial serine transporter during one-carbon metabolism, which is involved in the proliferation of cancer cells. However, the specific role of SFXN3 in HNSC remains unknown. In this study, we performed expression and survival analysis for SFXN3 in pan-cancer using data from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) and found that SFXN3 served as a potential oncogene in HNSC. Notably, SFXN3 expression was found to be positively associated with enriched tumor-infiltrating macrophages, other immune suppressive cells, and immune checkpoint expression and resistance to paclitaxel. Gene, clinical, and immune variables included in the univariate and multivariate analyses showed that SFXN3 expression was an independent risk factor. Moreover, the LINC01270/hsa-miR-29c-3p/SFXN3 axis was identified as the most likely upstream non-coding RNA-related pathway of SFXN3 in HNSC using bioinformatic analysis, expression analysis, correlation analysis, and survival analysis. Taken together, our findings demonstrated that a non-coding RNA-mediated high expression of SFXN3 is a prognostic biomarker and is associated with the immunosuppressive microenvironment in HNSC.
TLR2-induced CD8+ T-cell deactivation shapes dendritic cell differentiation in the bone marrow during sepsis
Authors: Antoni Anne-Charlotte , Pylaeva Ekaterina , Budeus Bettina , Jablonska Jadwiga , Klein-Hitpaß Ludger , Dudda Marcel , Flohé Stefanie B.
Published: September 2022

Sepsis is associated with profound immune dysregulation that increases the risk for life-threatening secondary infections: Dendritic cells (DCs) undergo functional reprogramming due to yet unknown changes during differentiation in the bone marrow (BM). In parallel, lymphopenia and exhaustion of T lymphocytes interfere with antigen-specific adaptive immunity. We hypothesized that there exists a link between T cells and the modulation of DC differentiation in the BM during murine polymicrobial sepsis. Sepsis was induced by cecal ligation and puncture (CLP), a model for human bacterial sepsis. At different time points after CLP, the BM and spleen were analyzed in terms of T-cell subpopulations, activation, and Interferon (IFN)-γ synthesis as well as the number of pre-DCs. BM-derived DCs were generated in vitro. We observed that naïve and virtual memory CD8+ T cells, but not CD4+ T cells, were activated in an antigen-independent manner and accumulated in the BM early after CLP, whereas lymphopenia was evident in the spleen. The number of pre-DCs strongly declined during acute sepsis in the BM and almost recovered by day 4 after CLP, which required the presence of CD8+ T cells. Adoptive transfer experiments and in vitro studies with purified T cells revealed that Toll-like receptor 2 (TLR2) signaling in CD8+ T cells suppressed their capacity to secrete IFN-γ and was sufficient to change the transcriptome of the BM during sepsis. Moreover, the diminished IFN-γ production of CD8+ T cells favored the differentiation of DCs with increased production of the immune-activating cytokine Interleukin (IL)-12. These data identify a novel role of CD8+ T cells in the BM during sepsis as they sense TLR2 ligands and control the number and function of de novo differentiating DCs.
Esaxerenone inhibits the macrophage-to-myofibroblast transition through mineralocorticoid receptor/TGF-β1 pathway in mice induced with aldosterone
Authors: Qiang Panpan , Hao Juan , Yang Fan , Han Yutong , Chang Yi , Xian Yunqian , Xiong Yunzhao , Gao Xiaomeng , Liang Lijuan , Shimosawa Tatsuo , Xu Qingyou
Published: September 2022

Renal fibrosis is the inevitable pathway of the progression of chronic kidney disease to end-stage renal disease, which manifests as progressive glomerulosclerosis and renal interstitial fibrosis. In a previous study, we observed severe interstitial fibrosis in the contralateral kidneys of 6-month unilateral ureteral obstruction (UUO) rats, which was accompanied by increased macrophage infiltration and phenotypic transformation; after eplerenone administration, these effects were reduced. Therefore, we hypothesized that this effect was closely related to mineralocorticoid receptor (MR) activation induced by the increased aldosterone (ALD) level. In this study, we used uninephrectomy plus continuous aldosterone infusion in mice to observe whether aldosterone induced macrophage-to-myofibroblast transition (MMT) and renal fibrosis and investigated the signaling pathways. Notably, aldosterone induced predominantly M1 macrophage-to-myofibroblast transition by activating MR and upregulating TGF-β1 expression, which promoted renal fibrosis. These effects were antagonized by the MR blocker esaxerenone. These findings suggest that targeting the MR/TGF-β1 pathway may be an effective therapeutic strategy for renal fibrosis.
mRNA vaccination drives differential mucosal neutralizing antibody profiles in naïve and SARS-CoV-2 previously-infected individuals
Authors: Longet Stephanie , Hargreaves Alexander , Healy Saoirse , Brown Rebecca , Hornsby Hailey R. , Meardon Naomi , Tipton Tom , Barnes Eleanor , Dunachie Susanna , Duncan Christopher J. A. , Klenerman Paul , Richter Alex , Turtle Lance , de Silva Thushan I. , Carroll Miles W.
Published: September 2022

Two doses of BNT162b2 mRNA vaccine induces a strong systemic SARS-CoV-2 specific humoral response. However, SARS-CoV-2 airborne transmission makes mucosal immune response a crucial first line of defense. Therefore, we characterized SARS-CoV-2-specific IgG responses induced by BNT162b2 vaccine, as well as IgG responses to other pathogenic and seasonal human coronaviruses in oral fluid and plasma from 200 UK healthcare workers who were naïve (N=62) or previously infected with SARS-CoV-2 (N=138) using a pan-coronavirus multiplex binding immunoassay (Meso Scale Discovery®). Additionally, we investigated the impact of historical SARS-CoV-2 infection on vaccine-induced IgG, IgA and neutralizing responses in selected oral fluid samples before vaccination, after a first and second dose of BNT162b2, as well as following a third dose of mRNA vaccine or breakthrough infections using the same immunoassay and an ACE2 inhibition assay. Prior to vaccination, we found that spike-specific IgG levels in oral fluid positively correlated with IgG levels in plasma from previously-infected individuals (Spearman r=0.6858, p<0.0001) demonstrating that oral fluid could be used as a proxy for the presence of plasma SARS-CoV-2 IgG. However, the sensitivity was lower in oral fluid (0.85, 95% CI 0.77-0.91) than in plasma (0.94, 95% CI 0.88-0.97). Similar kinetics of mucosal and systemic spike-specific IgG levels were observed following vaccination in naïve and previously-infected individuals, respectively. In addition, a significant enhancement of OC43 and HKU1 spike-specific IgG levels was observed in previously-infected individuals following one vaccine dose in oral fluid (OC43 S: p<0.0001; HKU1 S: p=0.0423) suggesting cross-reactive IgG responses to seasonal beta coronaviruses. Mucosal spike-specific IgA responses were induced by mRNA vaccination particularly in previously-infected individuals (71%) but less frequently in naïve participants (23%). Neutralizing responses to SARS-CoV-2 ancestral and variants of concerns were detected following vaccination in naïve and previously-infected participants, with likely contribution from both IgG and IgA in previously-infected individuals (correlations between neutralizing responses and IgG: Spearman r=0.5642, p<0.0001; IgA: Spearman r=0.4545, p=0.0001). We also observed that breakthrough infections or a third vaccine dose enhanced mucosal antibody levels and neutralizing responses. These data contribute to show that a previous SARS-CoV-2 infection tailors the mucosal antibody profile induced by vaccination.
Breakthrough infections with the omicron and delta variants of SARS-CoV-2 result in similar re-activation of vaccine-induced immunity
Authors: Søraas Arne , Grødeland Gunnveig , Granerud Beathe Kiland , Ueland Thor , Lind Andreas , Fevang Børre , Murphy Sarah L. , Huse Camilla , Nygaard Anders Benteson , Steffensen Anne Katrine , al-Baldawi Huda , Holberg-Petersen Mona , Andresen Lise Lima , Ågnes Camilla , Ranheim Trine , Schanke Ylva , Istre Mette , Dahl John Arne , Chopra Adity , Dudman Susanne , Kaarbø Mari , Andersen Jan Terje , Vaage Eline Benno , Tran Trung The , Vaage John Torgils , Michelsen Annika E. , Müller Fredrik , Aukrust Pål , Halvorsen Bente , Dahl Tuva B. , Holter Jan Cato , Lund-Johansen Fridtjof
Published: September 2022

Background

Results showing that sera from double vaccinated individuals have minimal neutralizing activity against Omicron have been interpreted as indicating the need for a third vaccine dose for protection. However, there is little information about early immune responses to Omicron infection in double vaccinated individuals.

Methods

We measured inflammatory mediators, antibodies to the SARS-CoV-2 spike and nucleocapsid proteins, and spike peptide-induced release of interferon gamma in whole blood in 51 double-vaccinated individuals infected with Omicron, in 14 infected with Delta, and in 18 healthy controls. The median time points for the first and second samples were 7 and 14 days after symptom onset, respectively.

Findings

Infection with Omicron or Delta led to a rapid and similar increase in antibodies to the receptor-binding domain (RBD) of Omicron protein and spike peptide-induced interferon gamma in whole blood. Both the Omicron- and the Delta-infected patients had a mild and transient increase in inflammatory parameters.

Interpretation

The results suggest that two vaccine doses are sufficient to mount a rapid and potent immune response upon infection in healthy individuals of with the Omicron variant.

Funding

The study was funded by the Oslo University Hospital, and by grants from The Coalition for Epidemic Preparedness Innovations, Research Council of Norway (no 312780, 324272), South-Eastern Norway Regional Health Authority (no 2019067, 2021071, 10357, 2021047, 33612, 2021087, 2017092), EU Horizon 2020 grant no 848099, a philantropic donation from Vivaldi Invest A/S, and The European Virus Archive Global.
Five decades of clinical assessment of whole-sporozoite malaria vaccines
Authors: Nunes-Cabaço Helena , Moita Diana , Prudêncio Miguel
Published: September 2022

In 1967, pioneering work by Ruth Nussenzweig demonstrated for the first time that irradiated sporozoites of the rodent malaria parasitePlasmodium bergheiprotected mice against a challenge with infectious parasites of the same species. This remarkable finding opened up entirely new prospects of effective vaccination against malaria using attenuated sporozoites as immunization agents. The potential for whole-sporozoite-based immunization in humans was established in a clinical study in 1973, when a volunteer exposed to X-irradiatedP. falciparumsporozoites was found to be protected against malaria following challenge with a homologous strain of this parasite. Nearly five decades later, much has been achieved in the field of whole-sporozoite malaria vaccination, and multiple reports on the clinical evaluation of such candidates have emerged. However, this process has known different paces before and after the turn of the century. While only a few clinical studies were published in the 1970’s, 1980’s and 1990’s, remarkable progress was made in the 2000’s and beyond. This article reviews the history of the clinical assessment of whole-sporozoite malaria vaccines over the last forty-nine years, highlighting the impressive achievements made over the last few years, and discussing some of the challenges ahead.
IL27 gene expression distinguishes multisystem inflammatory syndrome in children from febrile illness in a South African cohort
Authors: Spracklen Timothy F. , Mendelsohn Simon C. , Butters Claire , Facey-Thomas Heidi , Stander Raphaella , Abrahams Debbie , Erasmus Mzwandile , Baguma Richard , Day Jonathan , Scott Christiaan , Zühlke Liesl J. , Kassiotis George , Scriba Thomas J. , Webb Kate
Published: September 2022

Introduction

Multisystem inflammatory syndrome in children (MIS-C) is a severe acute inflammatory reaction to SARS-CoV-2 infection in children. There is a lack of data describing differential expression of immune genes in MIS-C compared to healthy children or those with other inflammatory conditions and how expression changes over time. In this study, we investigated expression of immune-related genes in South African MIS-C patients and controls.

Methods

The cohort included 30 pre-treatment MIS-C cases and 54 healthy non-inflammatory paediatric controls. Other controls included 34 patients with juvenile systemic lupus erythematosus, Kawasaki disease or other inflammatory conditions. Longitudinal post-treatment MIS-C specimens were available at various timepoints. Expression of 80 immune-related genes was determined by real-time quantitative PCR.

Results

A total of 29 differentially expressed genes were identified in pre-treatment MIS-C compared to healthy controls. Up-regulated genes were found to be overrepresented in innate immune pathways including interleukin-1 processing and pyroptosis. Post-treatment follow-up data were available for up to 1,200 hours after first treatment. All down-regulated genes and 17/18 up-regulated genes resolved to normal levels in the timeframe, and all patients clinically recovered. When comparing MIS-C to other febrile conditions, only IL27 expression could differentiate these two groups with high sensitivity and specificity.

Conclusions

These data indicate a unique 29-gene signature of MIS-C in South African children. The up-regulation of interleukin-1 and pyroptosis pathway genes highlights the role of the innate immune system in MIS-C. IL-27 is a potent anti-inflammatory and antiviral cytokine that may distinguish MIS-C from other conditions in our setting.
Analysis on the hotspot characteristics of bird diversity distribution along the continental coastline of China
Authors: Hou Peng , Bai Junjun , Chen Yan , Hou Jing , Zhao Jiajun , Ma Yutiao , Zhai Jun
Published: September 2022

Global climate change and disturbances from human activities lead to habitat loss and changes in habitat quality, resulting in a reduction in biodiversity. The continental coastline of China distributes some cities with highly developed economies and coastal wetlands with rich biodiversity, and both economic development and biodiversity conservation are important topics. In order to clarify the spatial distribution of bird biodiversity in coastal areas, based on the MaxEnt model and GIS spatial analysis, the distribution data of 488 species of birds and 15 environmental variables were used to simulate the suitable distribution areas of birds, and to analyze the spatial distribution and hotspots of bird biodiversity in coastal areas. The main findings of this study are as follows. (1) A total of 488 species in 249 genera of 21 orders and 81 families of birds were involved in the modeling of coastal areas. The main environmental factors affecting the potential distribution of birds in general are: land use, monthly mean diurnal temperature range, and precipitation of the driest month. (2) High value areas of bird richness are distributed in different locations in the four sea areas: In the Bohai Rim region, they are mainly distributed in the Liaohe Estuary Wetland in Liaoning Province, the vicinity of the Yongdingxin River and Haihe River in Tianjin, the eastern part of Tianjin, and the Yellow River and Yellow River Delta Wetland in Shandong Province; In the coastal area of the Yellow Sea, they are primarily found in Kunyu Mountain National Nature Reserve, Laoshan Provincial Nature Reserve in Shandong Province, and Yancheng Wetland Rare Birds National Nature Reserve in Jiangsu Province; In the coastal areas of the East China Sea, they are mainly found at the mouth of the Yangtze River, at the national nature reserve of Dongtan birds on Chongming Island, along the southeastern coast of Zhejiang Province, near the Min River and along the coast of Quanzhou in Fujian Province; In the coastal areas of the South China Sea, they are mainly distributed in the Pearl River Delta wetlands of Guangdong Province, the southeastern coastal areas of the Guangdong-Hong Kong-Macao Greater Bay Area, and the Shiwanda Mountain National Nature Reserve in Guangxi Province. (3) The spatial trends in the distribution of hotspots of birds of national priority protection in coastal areas are generally consistent, but more concentrated than the distribution of all birds. (4) After the high-value areas of bird richness were superimposed with protected areas, it was found that the intersecting area accounted for a small proportion of the protected area, and many areas near the inland had low bird richness. Finally, the findings provide references for bird biodiversity conservation and planning in coastal areas.
Phytoplankton photophysiology across tropical eddies: Deconvolving nutrient, light, and community signals
Authors: Liu Haoran , Xie Yuyuan , Browning Thomas J. , Xu Feipeng , Huang Bangqin
Published: September 2022

Fast repetition rate fluorometry (FRRf) based on active chlorophyll fluorescence is a powerful, noninvasive tool for studying phytoplankton physiological status at high spatial and temporal resolution. The South China Sea (SCS) is one of the largest tropical–subtropical marginal seas in the world, which plays an important role in modulating regional carbon budget and climate. In this study, underway in situ FRRf measurements were carried out throughout the outer continental shelf of the northern SCS, the basin of the northern SCS, the cyclonic eddy influenced domain in the western SCS, and the basin of the southeastern SCS. Pronounced diurnal variability of FRRf-derived parameters were observed, characterized by a large midday depression and slight nocturnal depression of the maximum quantum yield of photosystem II (Fv/Fm) and a slight increase in the functional absorption cross-section of photosystem II photochemistry (σPSII) at noon. Fv/Fm at the surface was typically as low as 0.1–0.3 and exhibited higher values (~0.4) where internal waves occurred. The cyclonic eddy increased Fv/Fm slightly, implying that it had a limited impact on surface phytoplankton photophysiology. With proper interpretation, FRRf has been a powerful tool to assess the physiological status of phytoplankton in the sea and to correlate that to ocean dynamics in an unprecedented fine scale.
Unraveling environmental drivers of chlorophyll seasonal and interannual variability in the East China Sea
Authors: Xu Yi , Wu Ying , Xiu Peng , Ge Jianzhong , Zhang Jing
Published: September 2022

Phytoplankton, the dominant marine primary producers, are considered highly sensitive indicators of ecosystem conditions and changes. The East China Sea (ECS) includes a variety of oceanic and coastal domains that collectively challenge our understanding of phytoplankton dynamics and controls. This study evaluates the seasonal and interannual variability of phytoplankton in the ECS and the underlying environmental determinants based on 22-year satellite chlorophyll (Chl-a) data and concurrent environmental variables. A seasonal spring bloom was found in the ECS, classically driven by increased stratification, which is associated with increases in sea surface temperature (SST), photosynthetically available radiation (PAR), net heat flux (NHF), and reduced wind mixing. The most significant Chl-a interannual variability was present in a triangular area surrounded by three SST fronts in the southern ECS during springtime. Anomalously high Chl-a (~30% increase) occurred with increased SST and NHF and enhanced wind mixing during negative Pacific Decadal Oscillation (PDO) and El Niño–Southern Oscillation (ENSO) modes. This seems to be contrary to the stratification control model, which fits the seasonal spring bloom observed in this region. More front activities during the negative PDO and ENSO could be associated with Chl-a increase in this triangular area. Contrary to this mixing control scenario, a significant Chl-a increase (~36% increase) also developed during the positive PDO and ENSO modes after 2014 under conditions of higher SST, NHF, and weaker wind mixing following the stratification control scenario. This study used biologically relevant objective regionalization of a heterogeneous area to elucidate phytoplankton bloom dynamics and controls. Our analyses highlight the triangular area in the ECS for its region-specific linkages between Chl-a and multiple climate-sensitive environmental drivers, as well as the potential structural and functional variability in this region.
Positive effects of replacing commercial feeds by fresh black soldier fly (Hermetia illucens) larvae in the diets of Pacific white shrimp (Litopenaeus vannamei): Immune enzyme, water quality, and intestinal microbiota
Authors: He Yuhang , Zhang Naida , Wang Aolin , Wang Sizhe , Che Yanjin , Huang Shu , Yi Qilin , Ma Yuexin , Jiang Yusheng
Published: September 2022

This study investigated the effects of replacing commercial feeds with fresh black soldier fly larvae (BSFL) on the immune enzyme activities, water quality in the culturing environment, and intestinal microbiota of Pacific white shrimp (Litopenaeus vannamei). Five different feeding regimes were designed, in which 0% (control group), 25%, 50%, 75%, and 100% commercial feeds were replaced with equal wet weight of fresh BSFL, respectively. The experiment lasted for 45 days, and the results showed that the serum T-NOS (total nitric oxide synthase), AKP (alkaline phosphatase), and ACP (acid phosphatase) activity were significantly increased in the BSFL25% group. However, the immune enzymes of the hepatopancreas decreased significantly in all the BSFL-containing groups compared to the control group. Total ammonia nitrogen concentrations throughout the experimental phase and nitrate concentrations in the middle and later phases of the experiment were negatively correlated with the replacement rate of fresh BSFL in the diet, whereas pH was positively correlated with the replacement rate of fresh BSFL in the diet. Proteobacteria and Bacteroidetes were dominant phyla in the intestines of shrimps, but the relative abundances of Proteobacteria and Firmicutes decreased, with those of Bacteroidetes and Planctomycetes increased in the BSFL-containing groups. Among them, higher relative abundances of potential probiotics such as Motilimonas, Shimia, Pseudoalteromonas, and Shewanella and lower relative abundance of genus Vibrio were observed in the fresh BSFL-containing groups. Furthermore, shrimps fed with BSFL-containing diets had higher bacterial richness and diversity in the intestines. In conclusion, a proper replacement of commercial feed with fresh BSFL had a positive effects on the immune-related enzyme activities, water quality, and intestinal health in the L. vannamei.
Light-level geolocation reveals the short-distance non-breeding movements and distribution of tufted puffins throughout the Northeast Pacific Ocean
Authors: Schaefer Anne L. , Gorman Kristen B. , Bishop Mary Anne
Published: September 2022

Comprehensive assessments of cumulative impacts to seabirds have been hindered by an incomplete understanding of temporal and spatial patterns in marine habitat use, particularly during the non-breeding season when seabirds can range widely across the global ocean. Alcids are an important component of the meso-predator biodiversity of the North Pacific Ocean, yet the non-breeding movement ecology and distribution for many of the Pacific Auk species remain poorly quantified. Recent and projected declines for historically robust populations of tufted puffin (Fratercula cirrhata) in Alaska highlight the importance of resolving aspects of the species’ non-breeding ecology, especially the pelagic phenology and distribution. We used light-level geolocation to quantify the annual at-sea distribution of tufted puffins between a major Gulf of Alaska nesting colony (Middleton Island) and heretofore unknown migration routes and wintering areas. Geolocator data from 42 complete migration routes of reproductive adult tufted puffins collected primarily between 2018-2020 revealed that both males and females were short-distance migrants, wintering on average 616 km from their breeding colony. Tufted puffins departed the breeding grounds in early September. Males made fewer stops and arrived earlier to wintering areas than females, however the arrival date to the wintering area was later in 2019 compared to 2018. Males took 30.5 ± 16.7 (± standard deviation) days in 2018 and 30.8 ± 24.6 days in 2019 to arrive at wintering areas. Conversely, females took 36.1 ± 16.8 days in 2018 and 59.8 ± 17.3 days in 2019 to arrive at wintering areas. Adult tufted puffins wintered primarily in the deep offshore waters of the eastern Gulf of Alaska and partially in the adjacent Northeast Pacific Ocean over a period of 151.9 days ± 31.6 with spring migrations starting by late March. Males and females showed consistent spatial distributions within seasons, especially during winter. Tufted puffins shifted southwards throughout the non-breeding season, similar to other Atlantic and Northeast Pacific alcids. Our study provides important information on the at-sea non-breeding phenology and distribution of tufted puffins, which can inform risk assessments for the species including vulnerability to spatially and temporally explicit marine pollution, disease, fisheries by-catch, and ocean-climate variability.
Untargeted serum metabolomics reveals specific metabolite abnormalities in patients with Crohn's disease
Authors: Liu Huanhuan , Xu Minmin , He Qiongzi , Wei Peng , Ke Mengying , Liu Shijia
Published: September 2022

Crohn's disease (CD) is a subtype of inflammatory bowel disease (IBD) characterized by skip intestinal lesions that can occur in any part of the gastrointestinal tract. Currently, the diagnosis of CD is based on clinical history, physical examination and complementary diagnostic tests. It is challenging for physicians to make a definitive diagnosis. This study aimed to analyze the variation in metabolites in CD serum and identify potential predictive biomarkers of CD diagnosis. We collected serum samples from 316 subjects, including patients with CD and healthy controls (HCs). Serum metabolomics was conducted using liquid chromatography coupled to mass spectrometry. Potential biomarkers were screened and evaluated by univariate and multivariate analyses. A panel of two metabolites (deoxycholic acid and palmitic amide) was identified as a specific biomarker of CD. Receiver operating characteristic analysis (ROC) showed that the panel had a sensitivity of 80.25% with a specificity of 95.54% in discriminating CD patients from healthy controls. The biomarkers identified are increased in CD compared with healthy controls. Our approach successfully identified serum biomarkers associated with CD patients. The potential biomarkers indicated that CD metabolic disturbance might be associated with bile acid biosynthesis, fatty acids and energy metabolism.
Functional consequence of myeloid ferritin heavy chain on acute and chronic effects of rhabdomyolysis-induced kidney injury
Authors: McCullough Kayla R. , Akhter Juheb , Taheri Mauhaun J. , Traylor Amie , Zmijewska Anna A. , Verma Vivek , Hudson Matthew C. , Sachdeva Abhishek , Erman Elise N. , Moore Kyle H. , George James F. , Bolisetty Subhashini
Published: September 2022

Acute kidney injury (AKI) is a serious complication of rhabdomyolysis that significantly impacts survival. Myoglobin released from the damaged muscle accumulates in the kidney, causing heme iron-mediated oxidative stress, tubular cell death, and inflammation. In response to injury, myeloid cells, specifically neutrophils and macrophages, infiltrate the kidneys, and mediate response to injury. Ferritin, comprised of ferritin light chain and ferritin heavy chain (FtH), is vital for intracellular iron handling. Given the dominant role of macrophages and heme-iron burden in the pathogenesis of rhabdomyolysis, we studied the functional role of myeloid FtH in rhabdomyolysis-induced AKI and subsequent fibrosis. Using two models of rhabdomyolysis induced AKI, we found that during the acute phase, myeloid FtH deletion did not impact rhabdomyolysis-induced kidney injury, cell death or cell proliferation, suggesting that tubular heme burden is the dominant injury mechanism. We also determined that, while the kidney architecture was markedly improved after 28 days, tubular casts persisted in the kidneys, suggesting sustained damage or incomplete recovery. We further showed that rhabdomyolysis resulted in an abundance of disparate intra-renal immune cell populations, such that myeloid populations dominated during the acute phase and lymphoid populations dominated in the chronic phase. Fibrotic remodeling was induced in both genotypes at 7 days post-injury but continued to progress only in wild-type mice. This was accompanied by an increase in expression of pro-fibrogenic and immunomodulatory proteins, such as transforming growth factor-β, S100A8, and tumor necrosis factor-α. Taken together, we found that while the initial injury response to heme burden was similar, myeloid FtH deficiency was associated with lesser interstitial fibrosis. Future studies are warranted to determine whether this differential fibrotic remodeling will render these animals more susceptible to a second AKI insult or progress to chronic kidney disease at an accelerated pace.
Planned mode of birth after previous cesarean section: A structured review of the evidence on the associated outcomes for women and their children in high-income setting
Authors: Fitzpatrick Kathryn E. , Quigley Maria A. , Kurinczuk Jennifer J.
Published: September 2022

In many high-income settings policy consensus supports giving pregnant women who have had a previous cesarean section a choice between planning an elective repeat cesarean section (ERCS) or planning a vaginal birth after previous cesarean (VBAC), provided they have no contraindications to VBAC. To help women make an informed decision regarding this choice, clinical guidelines advise women should be counseled on the associated risks and benefits. The most recent and comprehensive review of the associated risks and benefits of planned VBAC compared to ERCS in high-income settings was published in 2010 by the US Agency for Healthcare Research and Quality (AHRQ). This paper describes a structured review of the evidence in high-income settings that has been published since the AHRQ review and the literature in high-income settings that has been published since 1980 on outcomes not included in the AHRQ review. Three databases (MEDLINE, EMBASE, and PsycINFO) were searched for relevant studies meeting pre-specified eligible criteria, supplemented by searching of reference lists. Forty-seven studies were identified as meeting the eligibility criteria and included in the structured review. The review suggests that while planned VBAC compared to ERCS is associated with an increased risk of various serious birth-related complications for both the mother and her baby, the absolute risk of these complications is small for either birth approach. The review also found some evidence that planned VBAC compared to ERCS is associated with benefits such as a shorter length of hospital stay and a higher likelihood of breastfeeding. The limited evidence available also suggests that planned mode of birth after previous cesarean section is not associated with the child’s subsequent risk of experiencing adverse neurodevelopmental or health problems in childhood. This information can be used to manage and counsel women with previous cesarean section about their subsequent birth choices. Collectively, the evidence supports existing consensus that there are risks and benefits associated with both planned VBAC and ERCS, and therefore women without contraindications to VBAC should be given an informed choice about planned mode of birth after previous cesarean section. However, further studies into the longer-term effects of planned mode of birth after previous cesarean section are needed along with more research to address the other key limitations and gaps that have been highlighted with the existing evidence.
A randomized, open-label trial of combined nitazoxanide and atazanavir/ritonavir for mild to moderate COVID-19
Authors: Fowotade Adeola , Bamidele Folasade , Egbetola Boluwatife , Fagbamigbe Adeniyi F. , Adeagbo Babatunde A. , Adefuye Bolanle O. , Olagunoye Ajibola , Ojo Temitope O. , Adebiyi Akindele O. , Olagunju Omobolanle I. , Ladipo Olabode T. , Akinloye Abdulafeez , Onayade Adedeji , Bolaji Oluseye O. , Rannard Steve , Happi Christian , Owen Andrew , Olagunju Adeniyi
Published: September 2022

Background

The nitazoxanide plus atazanavir/ritonavir for COVID-19 (NACOVID) trial investigated the efficacy and safety of repurposed nitazoxanide combined with atazanavir/ritonavir for COVID-19.

Methods

This is a pilot, randomized, open-label multicenter trial conducted in Nigeria. Mild to moderate COVID-19 patients were randomly assigned to receive standard of care (SoC) or SoC plus a 14-day course of nitazoxanide (1,000 mg b.i.d.) and atazanavir/ritonavir (300/100 mg od) and followed through day 28. Study endpoints included time to clinical improvement, SARS-CoV-2 viral load change, and time to complete symptom resolution. Safety and pharmacokinetics were also evaluated (ClinicalTrials.gov ID: NCT04459286).

Results

There was no difference in time to clinical improvement between the SoC (n = 26) and SoC plus intervention arms (n = 31; Cox proportional hazards regression analysis adjusted hazard ratio, aHR = 0.898, 95% CI: 0.492–1.638, p = 0.725). No difference was observed in the pattern of saliva SARS-CoV-2 viral load changes from days 2–28 in the 35% of patients with detectable virus at baseline (20/57) (aHR = 0.948, 95% CI: 0.341–2.636, p = 0.919). There was no significant difference in time to complete symptom resolution (aHR = 0.535, 95% CI: 0.251–1.140, p = 0.105). Atazanavir/ritonavir increased tizoxanide plasma exposure by 68% and median trough plasma concentration was 1,546 ng/ml (95% CI: 797–2,557), above its putative EC90 in 54% of patients. Tizoxanide was undetectable in saliva.

Conclusion

Nitazoxanide co-administered with atazanavir/ritonavir was safe but not better than standard of care in treating COVID-19. These findings should be interpreted in the context of incomplete enrollment (64%) and the limited number of patients with detectable SARS-CoV-2 in saliva at baseline in this trial.

Clinical trial registration

[https://clinicaltrials.gov/ct2/show/NCT04459286], identifier [NCT04459286].
Expression of extracellular matrix components in the meibomian gland
Authors: Chen Di , Chen Xiaomin , Xie Hua-Tao , Hatton Mark P. , Liu Xiaowei , Liu Yang
Published: September 2022

Purpose

Extracellular matrix (ECM) is a key component of the stem cell local microenvironment. Our study aims to explore the periglandular distribution of major components of ECM in the Meibomian gland (MG).

Methods

Human eyelids and mouse eyelids were collected and processed for immunofluorescence staining.

Results

Human MG tissues stained positive for collagen IV α1, collagen IV α2, collagen IV α5, and collagen IV α6 around the acini and duct, but negative for collagen IV α3 and collagen IV α4. The mouse MG were stained positive for the same collagen IV subunits as early as postnatal day 15. Laminin α2, laminin β1 and perlecan stained the regions surrounding the acini and the acinar/ductal junction in the human MG, but not the region around the duct. Tenascin-C was found specifically located at the junctions between the acini and the central ducts. Neither agrin nor endostatin was found in the human MG tissues.

Conclusion

The ECM expresses specific components in different regions around the MG, which may play a role in MG stem cell regulation, renewal, and regeneration.
Twelve-year global publications on small incision lenticule extraction: A bibliometric analysis
Authors: Han Tian , Zhao Liang , Shen Yang , Chen Zhi , Yang Dong , Zhang Jiaoyan , Sekundo Walter , Shah Rupal , Tian Jinhui , Zhou Xingtao
Published: September 2022

Purpose

To analyze the development process of small incision lenticule extraction (SMILE) surgery in a 12-year period.

Methods

We conducted a literature search for SMILE research from 2011 to 2022 using the Science Citation Index Expanded (SCIE) of the Web of Science Core Collection (WoSCC). The VOS viewer, and CiteSpace software were used to perform the bibliometric analysis. Publication language, annual growth trend, countries/regions and institutions, journals, keywords, references, and citation bursts were analyzed.

Results

A total of 731 publications from 2011 to 2022 were retrieved. Annual publication records grew from two to more than 100 during this period. China had the highest number of publications (n = 326). Sixty-five keywords that appeared more than four times were classified into six clusters: femtosecond laser technology, dry eye, biomechanics, visual quality, complications, and hyperopia.

Conclusion

The number of literatures has been growing rapidly in the past 12 years. Our study provides a deep insight into publications on SMILE for researchers and clinicians with bibliometric analysis for the first time.
Effects of different additives on the bacterial community and fermentation mode of whole-plant paper mulberry silage
Authors: Wu Changrong , Sun Wentao , Huang Yuan , Dai Sheng , Peng Chao , Zheng Yulong , Chen Chao , Hao Jun
Published: September 2022

The purpose of this study was to investigate the effects of inoculation with two lactic acid bacteria (LAB) strains (Lacticaseibacillus rhamnosus and Lentilactobacillus buchneri) and the addition of four corn flour proportions (0, 3, 6, and 9%) in different treatments, on the composition and function of the bacterial community in whole-plant paper mulberry silage. The different treatments promoted Lactiplantibacillus, Lentilactobacillus, and Lacticaseibacillus growth, but the microbial species responsible for fermentation differed among the treatments. High species diversity and various Gram-negative bacteria, such as Flavitalea sp., Pantoea agglomerans, Acinetobacter pittii, Turicibacter sanguinis, and Ralstonia pickettii, were found in the uninoculated LAB treatments. A beneficial bacterium, Lactobacillus johnsonii, was discovered for the first time in whole-plant paper mulberry silage. LAB inoculation simplifies the microbial community structure, and beneficial Lactobacillus as a key species aggregates in the inoculated treatment group. However, L. rhamnosus inoculation alone may have limited bacteriostatic activity against in whole-plant paper mulberry silage. Compared with silage lacking corn flour, amino sugar and nucleotide sugar metabolism, galactose metabolism, the phosphotransferase system and the pentose phosphate pathway metabolic activity were increased in corn flour-containing silage. Whole-plant paper mulberry can be used as a high-quality silage to provide high-quality feed resources for sustainable ruminant livestock production. Moreover, additive use is necessary for preparing paper mulberry silage.