bluuebunny/crossref_metadata_2025 huggingface dataset:
Risk of malignancy in cytologically indeterminate thyroid nodules harboring thyroid stimulating hormone receptor mutations
Authors: Whitmer Dorota , Phay John E. , Holt Shelby , O’Donnell Benjamin , Nguyen Jay , Joseph Dennis , Chi Anthony , Wu Shuyang , Hao Yangyang , Huang Jing , Klopper Joshua P. , Kloos Richard T. , Kennedy Giulia C. , Shin Joyce
Published: December 2022

Objectives

To evaluate the frequency and risk of malignancy of TSHRpI568T mutations discovered in indeterminate thyroid nodules (ITN) within the Veracyte CLIA laboratory undergoing Afirma® Genomic Sequencing Classifier (GSC) testing, and to evaluate a broader cohort of TSHR variants and their categorization as Afirma GSC benign (GSC-B) or suspicious (GSC-S). Finally, we seek to assess the risk of malignancy (ROM) of this group of TSHR mutated ITN in the GSC-S category.

Methods

ITN submitted to Veracyte for Afirma GSC testing between October 2017 and February 2022 were analyzed for TSHR variants and rates of GSC-B and GSC-S were calculated based upon BIII or IV cytology, by TSHR variant codon amino acid (AA) substitution, age, and gender. For GSC-S samples, surgical pathology reports were requested, and the rate of malignancy was calculated.

Results

Five percent of the ITN samples harbored an isolated TSHR variant and 5% of those were classified as GSC-S. Among TSHRpI568T samples, 96% were GSC-B and of the GSC-S samples, 21% were malignant. Among an unselected group of TSHR, absent TSHRpI568T mutations, 16.3% of GSC-S samples were malignant, all but one with codon mutations in the transmembrane subdomains of the TSHR. This prompted a dedicated evaluation of transmembrane codons which revealed a malignancy rate of 10.7% among GSC-S nodules. In total, 13/85 (15.3%) TSHR mutated ITN with Afirma GSC-S results were found to be malignant.

Conclusions

TSHR variants are rare in ITN, and most are categorized as benign under Afirma GSC testing which carries a < 4% risk of malignancy. For GSC-S ITN with TSHR mutations, the risk of malignancy is ≥= 15%, which is clinically meaningful and may alter treatment or monitoring recommendations for patients.
Using MODIS data to track the long-term variations of dissolved oxygen in Lake Taihu
Authors: Liu Miao , Wang Li , Qiu Fangdao
Published: December 2022

Dissolved oxygen (DO) is crucial for the health of aquatic ecosystems, and plays an essential role in regulating biogeochemical processes in inland lakes. Traditional measurements of DO using the probe or analysis in a laboratory are time-consuming and cannot obtain data with high frequency and broad coverage. Satellites can provide daily/hourly observations within a broad scale and have been used as an important technique for aquatic environments monitoring. However, satellite-derived DO in waters is challenging due to its non-optically active property. Here, we developed a two-step model for retrieving DO concentration in Lake Taihu from Moderate Resolution Imaging Spectroradiometer (MODIS) Aqua images. A machine learning model (eXtreme gradient boosting) was developed to estimate DO from field water temperature, water clarity, and chlorophyll-a (Chla) (root-mean-square error (RMSE) = 0.98 mg L−1, mean absolute percentage error (MAPE) = 7.9%) and subsequently was validated on MODIS-derived water temperature, water clarity, and Chla matchups with a satisfactory accuracy (RMSE = 1.28 mg L−1, MAPE = 9.9%). MODIS-derived DO in Lake Taihu from 2002 to 2021 demonstrated that DO ranged from 7.2 mg L−1 to 14.2 mg L−1, with a mean value of 9.3 mg L−1. DO in the northern region was higher than in the central and southern regions, and higher in winter than in summer. We revealed that DO in this decade (2010–2021) was considerably lower than that in the last decade (2002–2009). Meanwhile, annual mean of DO increased in 2002–2009 and decreased from 2010 to 2021. The spatial distribution of DO in Lake Taihu was related to Chla and water clarity, while seasonal and interannual variations in DO resulted from air temperature primarily. This research enhances the potential use of machine learning approaches in monitoring non-optically active constituents from satellite imagery and indicates the possibility of long-term and high-range variations in more water quality parameters in lakes.
Uncertainty in coprophilous fungal spore concentration estimates
Authors: Perrotti Angelina G. , Ramiadantsoa Tanjona , O’Keefe Jennifer , Nuñez Otaño Noelia
Published: December 2022

The abundance of coprophilous (dung-inhabiting) fungal spores (CFS) in sedimentary records is an increasingly popular proxy for past megaherbivore abundance that is used to study megaherbivore-vegetation interactions, timing of megaherbivore population declines and extinctions, and the introduction of domesticated herbivores. This method often relies on counting CFS alongside pollen and tracers of known concentration such as exotic pollen or synthetic microspherules. Prior work has encouraged reporting CFS abundances as accumulation rates (spores/unit2/year) or concentration (spores/unit3) instead of percentages relative to the total pollen abundance, because CFS percentages can be sensitive to fluctuations in pollen influx. In this work, we quantify the uncertainty associated with estimating concentration values at different total counts and find that high uncertainty is associated with concentration estimates using low to moderate total counts (n = 20 to 200) of individual fungal spore types and tracers. We also demonstrate the effect of varying tracer proportions, and find that larger tracer proportions result in narrower confidence intervals. Finally, the probability of encountering a CFS spore from a specific taxon occurring in moderate concentrations (1,000 spores/unit2) dramatically decreases after a low tracer count (∼50). The uncertainties in concentration estimates caused by calculating tracer proportion are a likely cause of the high observed variance in many CFS time series, especially when CFS or tracer concentrations are low. Thus, we recommend future CFS studies increase counts and report the uncertainty surrounding concentration values. For some records, reporting spore data as presence/absence rather than concentrations or counts is preferable, such as when performing high counts is not feasible.
Nitrogen deposition in forests: Statistical modeling of total deposition from throughfall loads
Authors: Braun Sabine , Ahrends Bernd , Alonso Rocio , Augustin Sabine , García-Gómez Hector , Hůnová Iva , Karlsson Per Erik , Karlsson Gunilla Pihl , Schmitz Andreas , Thimonier Anne
Published: December 2022

Introduction

Nitrogen (N) gradient studies in some cases use N deposition in throughfall as measure of N deposition to forests. For evaluating critical loads of N, however, information on total N deposition is required, i.e., the sum of estimates of dry, wet and occult deposition.

Methods

The present paper collects a number of studies in Europe where throughfall and total N deposition were compared in different forest types. From this dataset a function was derived which allows to estimate total N deposition from throughfall N deposition.

Results

At low throughfall N deposition values, the proportion of canopy uptake is high and thus the underestimation of total deposition by throughfall N needs to be corrected. At throughfall N deposition values > 20 kg N ha–1 yr–1 canopy uptake is getting less important.

Conclusion

This work shows that throughfall clearly underestimates total deposition of nitrogen. With the present data set covering large parts of Europe it is possible to derive a critical load estimate from gradient studies using throughfall data.
Addressing inequalities in the identification and management of perinatal mental health difficulties: The perspectives of minoritised women, healthcare practitioners and the voluntary sector
Authors: Darwin Zoe , Blower Sarah L. , Nekitsing Chandani , Masefield Sarah , Razaq Rifat , Padgett Louise , Endacott Charlotte , Willan Kathryn , Dickerson Josie
Published: December 2022

Background

Perinatal mental health (PMH) difficulties affect approximately one in five birthing women. If not identified and managed appropriately, these PMH difficulties can carry impacts across generations, affecting mental health and relationship outcomes. There are known inequalities in identification and management across the healthcare pathway. Whilst barriers and facilitators have been identified there is a lack of clarity about how these relate to the avoidable and unfair inequalities experienced by various groups of women. Further research is required to understand how to address inequalities in PMH.

Aim

To understand the key factors that enable and hinder access to PMH care for women from minoritised groups across the PMH care pathway, and how these have been affected by the COVID-19 pandemic.

Methods

A sequential mixed-methods approach gathered views and experiences from stakeholders in one region in northern England. This included an online survey with 145 NHS healthcare practitioners and semi-structured interviews with 19 women from ethnic minority and/or socio-economically deprived backgrounds who had experienced PMH difficulties, and 12 key informants from the voluntary and community sector workforce. Quantitative data were analysed using descriptive statistics and framework analysis was applied to qualitative data.

Findings

Barriers and facilitators were mapped using a socio-technical framework to understand the role of (i) processes, (ii) people (organised as women, practitioners and others), (iii) technology, and (iv) the system as a whole in deepening or alleviating inequalities. Influences that were identified as pertinent to inequalities in identification and management included provision of interpreters, digital exclusion, stigma, disempowerment, distrust of services, practitioner attitudes, data capture, representation in the workforce, narrow rules of engagement and partnership working. Stakeholder groups expressed that several barriers were further compounded by the COVID-19 pandemic.

Discussion

The findings highlight the need for change at the system level to tackle inequalities across the PMH care pathway. Four inter-connected recommendations were developed to enable this systems change: building emotional safety between professionals and women; making PMH a part of core healthcare business; increasing cultural competency specific to PMH; and enhanced partnership working.
SARS-CoV-2 booster vaccination rescues attenuated IgG1 memory B cell response in primary antibody deficiency patients
Authors: Lin Frank J. , Doss Alexa Michelle Altman , Davis-Adams Hannah G. , Adams Lucas J. , Hanson Christopher H. , VanBlargan Laura A. , Liang Chieh-Yu , Chen Rita E. , Monroy Jennifer Marie , Wedner H. James , Kulczycki Anthony , Mantia Tarisa L. , O’Shaughnessy Caitlin C. , Raju Saravanan , Zhao Fang R. , Rizzi Elise , Rigell Christopher J. , Dy Tiffany Biason , Kau Andrew L. , Ren Zhen , Turner Jackson S. , O’Halloran Jane A. , Presti Rachel M. , Fremont Daved H. , Kendall Peggy L. , Ellebedy Ali H. , Mudd Philip A. , Diamond Michael S. , Zimmerman Ofer , Laidlaw Brian J.
Published: December 2022

Background

Although SARS-CoV-2 vaccines have proven effective in eliciting a protective immune response in healthy individuals, their ability to induce a durable immune response in immunocompromised individuals remains poorly understood. Primary antibody deficiency (PAD) syndromes are among the most common primary immunodeficiency disorders in adults and are characterized by hypogammaglobulinemia and impaired ability to mount robust antibody responses following infection or vaccination.

Methods

Here, we present an analysis of both the B and T cell response in a prospective cohort of 30 individuals with PAD up to 150 days following initial COVID-19 vaccination and 150 days post mRNA booster vaccination.

Results

After the primary vaccination series, many of the individuals with PAD syndromes mounted SARS-CoV-2 specific memory B and CD4+ T cell responses that overall were comparable to healthy individuals. Nonetheless, individuals with PAD syndromes had reduced IgG1+ and CD11c+ memory B cell responses following the primary vaccination series, with the defect in IgG1 class-switching rescued following mRNA booster doses. Boosting also elicited an increase in the SARS-CoV-2-specific B and T cell response and the development of Omicron-specific memory B cells in COVID-19-naïve PAD patients. Individuals that lacked detectable B cell responses following primary vaccination did not benefit from booster vaccination.

Conclusion

Together, these data indicate that SARS-CoV-2 vaccines elicit memory B and T cells in most PAD patients and highlights the importance of booster vaccination in immunodeficient individuals.
A metabolite attenuates neuroinflammation, synaptic loss and cognitive deficits induced by chronic infection of Toxoplasma gondii
Authors: He Yan , Xu Daxiang , Yan Ziyi , Wu Yongshuai , Zhang Yongsheng , Tian Xiaokang , Zhu Jinhang , Liu Zhuanzhuan , Cheng Wanpeng , Zheng Kuiyang , Yang Xiaoying , Yu Yinghua , Pan Wei
Published: December 2022

Background

Neurodegenerative diseases including AD is currently one of intractable problems globally due to the insufficiency of intervention strategies. Long-term infection of Toxoplasma gondii (T. gondii) can induce cognitive impairment in hosts, which is closely implicated in the pathogenesis of neurodegenerative diseases. Aconitate decarboxylase 1 (Acod1) and its produced metabolite itaconate (termed Acod1/itaconate axis), have recently attracted extensive interests due to its anti-inflammatory role in macrophages. However, whether the axis can influence cognitive function remains unknown.

Methods

A chronic T. gondii-infected mice (C57BL/6J) model was established via administration of cysts by gavage. Novel location (NL), novel object recognition (NOR), Y-maze spatial memory and nest building tests were used to evaluate the behavior performance. Transmission electron microscopy, immunofluorescence, RT-PCR, western-blotting and RNA sequencing were utilized to determine the pathological changes, neuroinflammation and transcription profile in hippocampus tissues post infection, respectively. Moreover, the protective effect of Acod1/itaconate axis in T. gondii-induced cognitive deficits was evaluated.

Results

We found that the latent infection of the parasite impaired the cognitive function, which was assessed behaviorally by novel location (NL), novel object recognition (NOR), Y-maze spatial memory and nest building tests. RNA sequencing of hippocampus showed that the infection downregulated the expression of genes related to synaptic plasticity, transmission and cognitive behavior. To our attention, the infection robustly upregulated the expression of genes associated with pro-inflammatory responses, which was characterized by microglia activation and disorder of Acod1/itaconate axis. Interestingly, administration of dimethyl itaconate (DI, an itaconate derivative with cell membrane permeability) could significantly ameliorate the cognitive deficits induced by T. gondii, which was proved by improvement of behavior performance and synaptic ultrastructure impairment, and lower accumulation of pro-inflammatory microglia. Notably, DI administration had a potential therapeutic effect on the cognitive deficits and synaptic impairment induced by the parasitic infection.

Conclusions

Overall, these findings provide a novel insight for the pathogenesis of T. gondii-related cognitive deficits in hosts, and also provide a novel clue for the potential therapeutic strategies.
Skin-homing basophils and beyond
Authors: Shibuya Rintaro , Kim Brian S.
Published: December 2022

Basophils have been implicated in type 2 inflammation and numerous disorders in the skin such as helminth infection, atopic dermatitis, and urticaria. Although similar in form and function to tissue-resident mast cells, classical studies on basophils have centered on those from the hematopoietic compartment. However, increasing studies in tissues like the skin demonstrate that basophils may take on particular characteristics by responding to unique developmental, chemotactic, and activation cues. Herein, we highlight how recent studies in barrier immunology suggest the presence of skin-homing basophils that harbor a unique identity in terms of phenotype, function, and motility. These concepts may uniquely inform how basophils contribute to diseases at multiple epithelial surfaces and our ability to therapeutically target the innate immune system in disease.
Novel neutralizing chicken IgY antibodies targeting 17 potent conserved peptides identified by SARS-CoV-2 proteome microarray, and future prospects
Authors: Li Jin , Liang Te , Hei Ailian , Wang Xiangbin , Li Huijun , Yu Xiaobo , Zhao Rui , Gao Peng , Fang Cong , Zhou Ji , Li Maogang , He Ellen , Skog Sven
Published: December 2022

Introduction

An approach toward novel neutralizing IgY polyclonal antibodies (N-IgY-pAb) against SARS-CoV-2 S-ECD was developed.

Material and methods

The novel N-IgY-pAb and its intranasal spray response against the wild type (“‘WH-Human 1”) SARS-CoV-2 virus, variants of Delta or Omicron were up to 98%. Unique virus peptides binding to N-IgY-pAb were screened by a SARS-CoV-2 proteome microarray.

Results

Seventeen mutation-free peptides with a Z-score > 3.0 were identified as potent targets from a total of 966 peptides. The new findings show that one is in the RBM domain (461LKPFERDISTEIYQA475 ), two are in the NTD domain (21RTQLPPAYTNSFTRG35, 291CALDPLSETKCTLKS305) four are in the C1/2-terminal (561PFQQFGRDIADTTDA575,571DTTDAVRDPQTLEIL585,581TLEILDITPCSFGGV595, 661ECDIPIGAGICASYQ675 ), three are in the S1/S2 border (741YICGDSTECSNLLLQ755, 811KPSKRSFIEDLLFNK825, 821LLFNKVTLADAGFIK835) one target is in HR2 (1161SPDVDLGDISGINAS1175) and one is in HR2-TM (1201QELGKYEQYIKWPWY1215). Moreover, five potential peptides were in the NSP domain: nsp3-55 (1361SNEKQEILGTVSWNL1375), nsp14-50 (614HHANEYRLYLDAYNM642, ORF10-3 (21MNSRNYIAQVDVVNFNLT38, ORF7a-1(1MKIILFLALITLATC15) and ORF7a-12 (1116TLCFTLKRKTE121).

Discussion and conclusion

We concluded that the N-IgY-pAb could effectively neutralize the SARS-CoV-2. The new findings of seventeen potent conserved peptides are extremely important for developing new vaccines and “cocktails” of neutralizing Abs for efficient treatments for patients infected with SARS-CoV-2.
Neuroinflammation in Huntington’s disease: From animal models to clinical therapeutics
Authors: Jia Qingqing , Li Shihua , Li Xiao-Jiang , Yin Peng
Published: December 2022

Huntington’s disease (HD) is a progressive neurodegenerative disease characterized by preferential loss of neurons in the striatum in patients, which leads to motor and cognitive impairments and death that often occurs 10-15 years after the onset of symptoms. The expansion of a glutamine repeat (>36 glutamines) in the N-terminal region of huntingtin (HTT) has been defined as the cause of HD, but the mechanism underlying neuronal death remains unclear. Multiple mechanisms, including inflammation, may jointly contribute to HD pathogenesis. Altered inflammation response is evident even before the onset of classical symptoms of HD. In this review, we summarize the current evidence on immune and inflammatory changes, from HD animal models to clinical phenomenon of patients with HD. The understanding of the impact of inflammation on HD would help develop novel strategies to treat HD.
Serum cytokine profiling reveals different immune response patterns during general and severe Mycoplasma pneumoniae pneumonia
Authors: Zhang Zhikun , Dou Haiwei , Tu Peng , Shi Dawei , Wei Ran , Wan Ruijie , Jia Chunmei , Ning Lihua , Wang Dongmei , Li Jing , Dong Yan , Xin Deli , Xu Baoping
Published: December 2022

Mycoplasma pneumoniae (MP) is an important human pathogen that mainly affects children causing general and severe Mycoplasma pneumoniae pneumonia (G/SMPP). In the present study, a comprehensive immune response data (33 cytokines) was obtained in school-age children (3–9 years old) during MPP, aiming to analyze the immune response patterns during MPP. At acute phase, changes of cytokines were both detected in GMPP (24/33) and SMPP (23/33) groups compared to the healthy group (p < 0.05), with 20 identical cytokines. Between MPP groups, the levels of 13 cytokines (IL-2, IL-10, IL-11, IL-12, IL-20, IL-28A, IL-32, IL-35, IFN-α2, IFN-γ, IFN-β, BAFF, and TSLP) were higher and three cytokines (LIGHT, OPN and CHI3L1) were lower in the SMPP group than in the GMPP group (p < 0.05). Function analysis reveals that macrophage function (sCD163, CHI3L1) are not activated in both MPP groups; difference in regulatory patterns of T cells (IL26, IL27, OPN, LIGHT) and defective activation of B cells (BAFF) were detected in the SMPP group compared to the GMPP group. Besides, the level of osteocalcin; sIL-6Rβ and MMP-2 are both decreased in MPP groups at acute and convalescent phases compared to the healthy group, among which the levels of sIL-6Rβ and MMP-2 showed negative correlations (p < 0.1) to the application of bronchial lavage in SMPP group, indicating their roles in the development of MPP. At the convalescent phase, more cytokines recovered in GMPP (18) than SMPP (11), revealing better controlled immune response during GMPP. These results reveal different immune response patterns during GMPP and SMPP. In addition, the differentiated cytokines may serve as potential indicators of SMPP; early intervention on immune response regulations may be helpful in reducing the severity of SMPP.
The safety of COVID-19 vaccines in patients with myasthenia gravis: A scoping review
Authors: Peng Siyang , Tian Yukun , Meng Linghao , Fang Ruiying , Chang Weiqian , Yang Yajing , Li Shaohong , Shen Qiqi , Ni Jinxia , Zhu Wenzeng
Published: December 2022

Background

COVID-19 vaccines are required for individuals with myasthenia gravis (MG), as these patients are more likely to experience severe pneumonia, myasthenia crises, and higher mortality rate. However, direct data on the safety of COVID-19 vaccines in patients with MG are lacking, which results in hesitation in vaccination. This scoping was conducted to collect and summarize the existing evidence on this issue.

Methods

PubMed, Cochrane Library, and Web of Science were searched for studies using inclusion and exclusion criteria. Article titles, authors, study designs, demographics of patients, vaccination information, adverse events (AEs), significant findings, and conclusions of included studies were recorded and summarized.

Results

Twenty-nine studies conducted in 16 different countries in 2021 and 2022 were included. Study designs included case report, case series, cohort study, cross-sectional study, survey-based study, chart review, and systemic review. A total of 1347 patients were included. The vaccines used included BNT162b2, mRNA-1273, ChAdOx1 nCoV-19, inactivated vaccines, and recombinant subunit vaccines. Fifteen case studies included 48 patients reported that 23 experienced new-onset, and five patients experienced flare of symptoms. Eleven other types of studies included 1299 patients reported that nine patients experienced new-onset, and 60 participants experienced flare of symptoms. Common AEs included local pain, fatigue, asthenia, cephalalgia, fever, and myalgia. Most patients responded well to treatment without severe sequelae. Evidence gaps include limited strength of study designs, type and dose of vaccines varied, inconsistent window of risk and exacerbation criteria, limited number of participants, and lack of efficacy evaluation.

Conclusion

COVID-19 vaccines may cause new-onset or worsening of MG in a small proportion of population. Large-scale, multicenter, prospective, and rigorous studies are required to verify their safety.
The game between host antiviral innate immunity and immune evasion strategies of senecavirus A - A cell biological perspective
Authors: Zhao Kuan , Zhang Shixia , Liu Xiaona , Guo Xiaoran , Guo Zhaomeng , Zhang Xiaozhan , Yuan Wanzhe
Published: December 2022

Innate immunity is the first line of the cellular host to defend against viral infection. Upon infection, viruses can be sensed by the cellular host’s pattern recognition receptors (PRRs), leading to the activation of the signaling cascade and the robust production of interferons (IFNs) to restrict the infection and replication of the viruses. However, numerous cunning viruses have evolved strategies to evade host innate immunity. The senecavirus A (SVA) is a newly identified member of the Picornaviridae family, causing severe vesicular or ulcerative lesions on the oral mucosa, snout, coronary bands, and hooves of pigs of different ages. During SVA infection, the cellular host will launch the innate immune response and various physiological processes to restrict SVA. In contrast, SVA has evolved several strategies to evade the porcine innate immune responses. This review focus on the underlying mechanisms employed by SVA to evade pattern recognition receptor signaling pathways, type I interferon (IFN-α/β) receptor (IFNAR) signaling pathway, interferon-stimulated genes (ISGs) and autophagy, and stress granules. Deciphering the antiviral immune evasion mechanisms by SVA will enhance our understanding of SVA’s pathogenesis and provide insights into developing antiviral strategies and improving vaccines.
Targeting cancer-specific metabolic pathways for developing novel cancer therapeutics
Authors: Pal Soumik , Sharma Amit , Mathew Sam Padalumavunkal , Jaganathan Bithiah Grace
Published: December 2022

Cancer is a heterogeneous disease characterized by various genetic and phenotypic aberrations. Cancer cells undergo genetic modifications that promote their proliferation, survival, and dissemination as the disease progresses. The unabated proliferation of cancer cells incurs an enormous energy demand that is supplied by metabolic reprogramming. Cancer cells undergo metabolic alterations to provide for increased energy and metabolite requirement; these alterations also help drive the tumor progression. Dysregulation in glucose uptake and increased lactate production via “aerobic glycolysis” were described more than 100 years ago, and since then, the metabolic signature of various cancers has been extensively studied. However, the extensive research in this field has failed to translate into significant therapeutic intervention, except for treating childhood-ALL with amino acid metabolism inhibitor L-asparaginase. Despite the growing understanding of novel metabolic alterations in tumors, the therapeutic targeting of these tumor-specific dysregulations has largely been ineffective in clinical trials. This chapter discusses the major pathways involved in the metabolism of glucose, amino acids, and lipids and highlights the inter-twined nature of metabolic aberrations that promote tumorigenesis in different types of cancer. Finally, we summarise the therapeutic interventions which can be used as a combinational therapy to target metabolic dysregulations that are unique or common in blood, breast, colorectal, lung, and prostate cancer.
Determination of temperature-dependent otolith oxygen stable isotope fractionation on chum salmon Oncorhynchus keta based on rearing experiment
Authors: Gou Yuxiao , Higuchi Tomihiko , Iino Yuki , Nagasaka Tsuyoshi , Shimizu Yuichi , Shirai Kotaro , Kitagawa Takashi
Published: December 2022

Reconstruction of water temperatures experienced by marine fishes using otolith oxygen stable isotopes (δ18O) as natural thermometers has been proven to be a useful approach for estimating migration routes or movement patterns. This method is based on the mechanism that the equilibrium fractionation of δ18Ootolith against ambient water exhibits a species-specific thermal sensitivity during the process of otolith aragonitic CaCO3 precipitation. In this study, a laboratory-controlled rearing experiment was conducted to determine the temperature dependency of δ18O fractionation on the anadromous fish species, chum salmon (Oncorhynchus keta), of which the detailed migration routes have not been elucidated yet. To test that temperature was the only factor affecting δ18Ootolith fractionation, this study ensured a relatively stable rearing condition, evaluated the isotope composition of the rearing water, and analyzed carbon isotope (δ13Cotolith) to examine the potential effect of kinetic and metabolic isotopic fractionations. The δ18Ootolith fractionation equation on chum salmon was thereby determined within a temperature range of 9–20°C and was indistinguishable from the equation of synthetic aragonite; The δ13Cotolith was affected by both physiological processes and δ13CDIC; In lower temperatures settings, both oxygen and carbon isotopes depleted simultaneously. This study suggests that the chum salmon species-specific oxygen isotope fractionation equation could be used on reconstruction of temperature history and also throw insights into understanding the incorporation of oxygen and carbon sources during calcification process for otoliths.
Development and applications of chromosome-specific cytogenetic BAC-FISH probes in Larimichthys crocea
Authors: Zhang Jianpeng , Xie Jingyi , Liu Bo , Wang Zhiyong , Wang Yilei , Jiang Yonghua , Zhang Jing , Cai Mingyi
Published: December 2022

Large yellow croaker Larimichthys crocea (Richardson) is an important member in family Sciaenidae, and one of most productive mariculture fishes in China. Fluorescence in situ hybridization is a useful tool for cytogenetics and genomics research. Here, we demonstrated that bacterial artificial chromosome (BAC) clones could be used to identify individual chromosomes in large yellow croaker, and also to study chromosome evolution in the related species. By using BAC paired-end sequencing and sequence alignment, 435 BAC clones were anchored to 24 pseudochromosomes of large yellow croaker genome. Among them, 72 BAC clones with low repeat content were selected and passed PCR test, and then grouped by chromosome for FISH test. As a results, there were 67 BAC clones, 2 to 3 BAC clones per chromosome, generated specific and stable signal at expected position. Then, a dual-color FISH probe cocktail composed of 48 of these BAC clones was formulated and used to hybridize metaphase chromosome spreads, resulting in distinct signal patterns on each chromosome pair, which help to distinguish all chromosomes in the metaphase spreads of large yellow croaker. The chromosome-specific BAC-FISH probes were also applied to a close relative of large yellow croaker, Collichthys lucidus, demonstrating that its Y chromosome originated from the fusion of Chr.1 and Chr.7. Thus, our study provides the first set of chromosome-specific FISH probes in family Sciaenidae, which will play an important role in cytogenetics and genomics research in the family.
Risk stratification in patients with upper gastrointestinal submucosal tumors undergoing submucosal tunnel endoscopic resection
Authors: Lv Yong , Li Shaohua , Lv Xiuhe , Liu Qing , Zheng Yu , Su Yang , Yang Changbin , Pan Yanglin , Yao Liping , Xie Huahong
Published: December 2022

Background

A substantial heterogeneity exists in patients with upper gastrointestinal submucosal tumors (SMTs). This study aimed to identify predictors of long procedure time (≥60 min), occurrence of procedure-related complications, and long hospital stay (≥6 days) in patients with SMTs undergoing submucosal tunnel endoscopic resection (STER) and stratify risk based on the predictors.

Methods

Sixty-six consecutive patients with upper gastrointestinal SMTs undergoing STER between January 2013 and December 2018 were retrospectively included. Binary logistic regression models were developed to identify predictors of outcomes. Receiver operating characteristic (ROC) curves were constructed to evaluate the discrimination of tumor size.

Results

Complete resection and en bloc resection of tumor were achieved in 66 (100%) and 64 patients (97%), respectively. Twenty-seven patients (41%) had a long procedure time, 10 (15%) developed STER-related complications, and 17 (26%) had a long hospital stay. On multivariable analysis, tumor size was an independent predictor of long procedure time (OR 1.37, 95% CI 1.13–1.67; p = 0.001), occurrence of complications (OR 1.06, 95% CI 1.01–1.10; p = 0.012), and long hospital stay (OR 1.05, 95% CI 1.01–1.09; p = 0.035). ROC curves identified a tumor of size 25 mm as the best cutoff; those who had a tumor above this value had a 76-fold risk of long procedure time, 8.56-fold risk of occurrence of complications, and 6.35-fold risk of long hospital stay.

Conclusion

Patients with a tumor size ≥25 mm had longer procedure time, higher risk of STER-related complications, and longer hospital stay; therefore, they should be classified as a high-risk group.
Efficacy of topical and systemic treatments for atopic dermatitis on pruritus: A systematic literature review and meta-analysis
Authors: Rodriguez-Le Roy Youna , Ficheux Anne-Sophie , Misery Laurent , Brenaut Emilie
Published: December 2022

Introduction

Pruritus is a major and burdensome symptom in atopic dermatitis (AD). The number of systemic treatments available for AD has increased recently, enabling improved patient relief.

Objective

To evaluate the effect of AD treatments on pruritus.

Methods

A systematic literature review and a meta-analysis were conducted to evaluate and compare the effects of treatment used in AD on pruritus. PubMed and Embase databases were searched to find articles published between January 1990 and December 2021. Topical and systemic treatments were studied in patients aged ≥10 years.

Results

Among the 448 articles identified, 56 studies were retained in the systematic review. A total of 15 studies evaluated topical treatments: topical corticosteroids (TCS; 2), calcineurin inhibitors (6), PDE4 inhibitors (3), and Jak inhibitors (4). A total of five studies were included in the meta- analysis. All treatments had a positive effect on pruritus, with a mean overall reduction of 3.32/10, 95% IC [2.32–4.33]. The greatest reduction was observed with halometasone (mean: 4.75), followed by tofacitinib 2% (mean: 4.38). A total of 41 studies evaluated systemic therapies: cyclosporine (6), phototherapy (5), azathioprine (2), dupilumab (9), anti-IL 13 (5), nemolizumab (3), Jak inhibitors (9), mepolizumab (1), and apremilast (1). A total of 17 studies were included in 2 meta-analyses according to the concomitant use or not of TCS. In the meta-analysis without TCS, the overall decrease was 3.07/10, 95% IC [2.58–3.56]. The molecules with the highest efficacy on pruritus were upadacitinib 30 mg (mean: 4.90) and nemolizumab (mean: 4.81).

Discussion

The therapeutic arsenal for AD has increased rapidly, and many molecules are under development. The primary endpoint of clinical trials is most often a score that assesses the severity of AD; however, the assessment of pruritus is also essential. The majority of molecules have a positive effect on pruritus, but the improvement varies between them. Efficacy on pruritus is not always correlated with efficacy on AD lesions; therefore, these two criteria are crucial to evaluate. The limitations of this study were the heterogeneity in the assessment of pruritus, the moment of the assessment, and the concomitant application of TCS or not for studies evaluating systemics. In the future, it would be useful to use standardized criteria for assessing pruritus.
Touching body, soul, and spirit? Understanding external applications from integrative medicine: A mixed methods systematic review
Authors: Mühlenpfordt Inga , Blakeslee Sarah B. , Everding Janina , Cramer Holger , Seifert Georg , Stritter Wiebke
Published: December 2022

Introduction

External applications from anthroposophic medicine (EAAM) are touch-based applications such as rhythmical massages, embrocations, and compresses that serve as components of complementary treatment concepts for various diseases. The aim of this review is to gain an understanding of typical indications and outcomes and to systematically assess the effectiveness and safety of EAAM.

Materials and methods

Medline/PubMed, CINAHL, the Cochrane Library, Embase, and PsycINFO were searched through May 2021 and supplemented by searches in specialized databases and personal requests to experts in the field. Studies and case reports on EAAM in patients, as well as healthy individuals, were included in the qualitative synthesis. Outcome parameters depending on each study were grouped as effect themes and assigned to study clusters using Thematic Analysis for a thematic overview of effect patterns.

Results

Four RCTs, 7 cohort studies, 1 mixed-methods, 1 retrospective, 4 qualitative studies, 3 case series, and 25 case reports on EAAM were identified. The analysis indicated various effects of EAAM on physiological as well as psychological health indicators and patterns of effect development. Study quality was found to be high for only 2 studies, and moderate for 1 study, and all remaining 45 studies showed a moderate or high risk of bias or were not ratable with used rating tools.

Conclusion

The included studies present a wide range of potential indications for EAAM, while showing methodological drawbacks. To determine whether EAAM can be considered an effective treatment option, clinical studies exploring the effect of different EAAM modalities on defined patient groups are recommended for the future.

Systematic review registration

[https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=214030], identifier [CRD42020214030].
Plant quercetin degradation by gut bacterium Raoultella terrigena of ghost moth Thitarodes xiaojinensis
Authors: Liu Guiqing , Cao Li , Han Richou
Published: December 2022

Associated microbes of several herbivorous insects can improve insect fitness. However, the contribution of specific insect gut bacterium to plant toxin toxification for its host fitness remains scarce. Here, a gut bacterium Raoultella terrigena from the ghost moth Thitarodes xiaojinensis larvae was identified. This bacterium grew unhindered in the presence of Polygonum viviparum, which is a natural food for ghost moth larvae but showed significant growth inhibition and toxicity against Spodoptera litura. S. litura reared on artificial diets containing 5, 15 and 25% P. viviparum powder after 7 days coculture with R. terrigena were found to have shorter larval and pupal durations than on the diets containing P. viviparum powder but without R. terrigena coculture. HPLC analysis revealed that the content of quercetin in mineral medium containing 15% P. viviparum powder after 7 days coculture with R. terrigena was significantly decreased (79.48%) as compared with that in P. viviparum powder without R. terrigena coculture. In vitro fermentation further verified that R. terrigena could degrade 85.56% quercetin in Lucia-Bertani medium. S. litura reared on artificial diets containing 0.01, 0.05 and 0.1 mg/g quercetin after 48 h coculture with R. terrigena were also found to have shorter larval, prepupal and pupal durations, as well as higher average pupal weight and adult emergence rate than on the diets containing quercetin, but without R. terrigena coculture. In addition, R. terrigena was detected in the bud and root tissues of the sterilized P. viviparum, indicating that T. xiaojinensis larvae might acquire this bacterium through feeding. These results demonstrate that the gut bacteria contribute to the degradation of plant toxic molecules to improve the development of herbivorous insects and provide fundamental knowledge for developing effective methods for beneficial insect rearing and pest control.
Comparison of physiochemical attributes, microbial community, and flavor profile of beef aged at different temperatures
Authors: Yu Haojie , Zhang Songshan , Liu Xiaochang , Lei Yuanhua , Wei Meng , Liu Yinchu , Yang Xiaodong , Xie Peng , Sun Baozhong
Published: December 2022

Beef aging for tenderness and flavor development may be accelerated by elevated temperature. However, little to no research has been undertaken that determines how this affects other important meat quality characteristics and microbial community. This study aims to decrease aging time by increasing temperature. Beef were aged and vacuum packaged at 10 and 15°C, and the effects of increased temperature on meat physiochemical attributes, microbial community, and flavor profile were monitored. The shear force decreased with aging in all temperature and showed the higher rate at elevated temperatures compare to 4°C. The beef aged at elevated temperatures (10 or 15°C) for 5 days showed equivalent shear force value to the beef aged at 4°C for 10 days (p  >  0.05), however, the final tenderness was not affected by the elevated temperature. The beef aged at elevated temperatures showed a significantly higher cooking loss and less color stability compared to 4°C (p  <  0.05). The total volatile basic nitrogen and aerobic plate count increased (p  <  0.05) faster at elevated temperatures compare to 4°C. Carnobacterium, Lactobacillus and Hafnia–Obesumbacterium were the dominant genus in the beef samples aged at 4, 10, and 15°C, respectively. In addition, the contents of isobutyraldehyde, 3-methylbutyraldehyde, 2-methylbutyraldehyde, and 3-methylbutanol were higher than aged at 4°C (p  <  0.05). Therefore, these results suggest that application of elevated aged temperatures could shorten required aging time prior while not adversely affecting meat quality. In turn, this will result in additional cost savings for meat processors.
Isolation and characterization of a high-efficiency algicidal bacterium Pseudoalteromonas sp. LD-B6 against the harmful dinoflagellate Noctiluca scintillans
Authors: Wang Junyue , Yin Xueyao , Xu Mingyang , Chen Yifan , Ji Nanjing , Gu Haifeng , Cai Yuefeng , Shen Xin
Published: December 2022

The dinoflagellate Noctiluca scintillans is a harmful algal species that is globally distributed and poses a certain threat to marine ecosystems. Recent research has shown that the application of algicidal bacteria is a promising method to prevent and control such harmful algal blooms (HABs), given its advantages of safety and efficiency. In this study, a strain of algicidal bacterium LD-B6 with high efficiency against N. scintillans was isolated from the coastal waters of Lianyungang, China. 16S rDNA sequence analysis showed that the strain LD-B6 belongs to the genus Pseudoalteromonas. Furthermore, the algicidal effect of LD-B6 on N. scintillans was investigated. The results showed that strain LD-B6 exerted strong algicidal activity against N. scintillans. After 12 h of bacterial culture addition to algal cultures at a 2% final volume rate, the algicidal activity reached 90.5%, and the algicidal activity of LD-B6 was influenced by the density of N. scintillans. In addition, the algicidal bacterium LD-B6 was found to indirectly lyse algal cells by secreting extracellular compounds. These algicidal compounds were stable, indicating that they are not proteins. Importantly, strain LD-B6 was broadly general, showing varying degrees of lysing effects against five of the six algal species tested. On the basis of the described studies above, the algicidal powder was also initially developed. In summary, the isolated bacterial strain LD-B6 shows the potent algicidal capability to serve as a candidate algicidal bacterium against N. scintillans blooms.
Study on the drug resistance and pathogenicity of Escherichia coli isolated from calf diarrhea and the distribution of virulence genes and antimicrobial resistance genes
Authors: Jia Yan , Mao Wei , Liu Bo , Zhang Shuangyi , Cao Jinshan , Xu Xiaojing
Published: December 2022

Introduction

The unscientific and irrational use of antimicrobial drugs in dairy farms has led to the emergence of more serious drug resistance in Escherichia coli.

Methods

In this study, cases of calf diarrhea in cattle farms around the Hohhot area were studied, and Escherichia coli were identified by PCR and biochemical methods, while the distribution of virulence and drug resistance genes of the isolates was analyzed.

Results

The results showed that 21 strains of Escherichia coli were isolated from the diseased materials, and the isolation rate was 60%. The isolated strains belong to 15 ST types. The drug resistance levels of the isolated strains to 20 kinds of antimicrobial agent viz., penicillin, ampicillin, cefotaxime, cefepime, cefoxitin, and ceftriaxone were more than 50%. The resistance rate to meropenem was 10%. The resistance rates to tetracycline and doxycycline were 33% and 29%, to ciprofloxacin, levofloxacin and enrofloxacin were 48%, 33%, and 33%, to amikacin, kanamycin and gentamicin were 19%, 24% and 38%, to cotrimoxazole and erythromycin were 48% and 15%, to florfenicol, chloramphenicol and polymyxin B were 29%, 33%, and 5%. Nine strains of pathogenic calf diarrhea Escherichia coli were isolated by mouse pathogenicity test. The detection rates of virulence genes for the adhesion class were fimC (95%), IuxS (95%), eaeA (76%), fimA (62%), ompA (52%), and flu (24%). The detection rates for iron transporter protein like virulence genes were iroN (33%), iutA (19%), fyuA (14%), irp5 (9.5%), Iss (9.5%), and iucD (9.5%). The detection rates for toxin-like virulence genes were phoA (90%), Ecs3703 (57%), ropS (33%), hlyF (14%), and F17 (9.5%). The detection rates of tetracycline resistance genes in isolated strains were tetB (29%), tetA (19%) and tetD (14%). The detection rates for fluoroquinolone resistance genes were parC (Y305H, P333S, R355G) (9.5%), gyrA (S83L, D87N) (28%), qnrD (43%), and qnrS (9.5%). The detection rates for β-lactam resistance genes were blaCTX–M (29%), blaTEM (29%), and blaSHV (9.5%). The detection rates for aminoglycoside resistance genes were strA-B (57%), aacC (33%), aac(3′)-IIa (29%), and aadAI (24%). The detection rates of chloramphenicol resistance genes floR and sulfa resistance genes sul2 were 24 and 33%.

Conclusion

Pathogenic Escherichia coli causing diarrhea in calves contain abundant virulence genes and antibiotic resistance genes.
ERK phosphorylation disrupts the intramolecular interaction of capicua to promote cytoplasmic translocation of capicua and tumor growth
Authors: Park Jongmin , Park Guk-Yeol , Lee Jongeun , Park Joonyoung , Kim Soeun , Kim Eunjeong , Park Seung-Yeol , Yoon Jong Hyuk , Lee Yoontae
Published: December 2022

Activation of receptor tyrosine kinase signaling inactivates capicua (CIC), a transcriptional repressor that functions as a tumor suppressor, via degradation and/or cytoplasmic translocation. Although CIC is known to be inactivated by phosphorylation, the mechanisms underlying the cytoplasmic translocation of CIC remain poorly understood. Therefore, we aimed to evaluate the roles of extracellular signal-regulated kinase (ERK), p90RSK, and c-SRC in the epidermal growth factor receptor (EGFR) activation-induced cytoplasmic translocation of CIC and further investigated the molecular basis for this process. We found that nuclear ERK induced the cytoplasmic translocation of CIC-S. We identified 12 serine and threonine (S/T) residues within CIC, including S173 and S301 residues that are phosphorylated by p90RSK, which contribute to the cytoplasmic translocation of CIC-S when phosphorylated. The amino-terminal (CIC-S-N) and carboxyl-terminal (CIC-S-C) regions of CIC-S were found to interact with each other to promote their nuclear localization. EGF treatment disrupted the interaction between CIC-S-N and CIC-S-C and induced their cytoplasmic translocation. Alanine substitution for the 12 S/T residues blocked the cytoplasmic translocation of CIC-S and consequently enhanced the tumor suppressor activity of CIC-S. Our study demonstrates that ERK-mediated disruption of intramolecular interaction of CIC is critical for the cytoplasmic translocation of CIC, and suggests that the nuclear retention of CIC may represent a strategy for cancer therapy.