bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetic manipulation of the interconversion between diacylglycerols and triacylglycerols in Rhodosporidium toruloides
Authors: Zhang Yue , Zhang Sufang , Chu Yadong , Zhang Qi , Zhou Renhui , Yu Di , Wang Shuang , Lyu Liting , Xu Guowang , Zhao Zongbao Kent
Published: October 2022

The basidiomycetous yeast Rhodosporidium toruloides (R. toruloides) is an excellent producer for neutral lipids, including triacylglycerols (TAG). Partially because genetic tools for this yeast were less developed, limited efforts were shown to explore its capacity for the production of higher-value lipids such as diacylglycerols (DAG). Here, four genes linked to the interconversion between DAG and TAG were manipulated to promote the production of DAG and free fatty acids (FFA). Among them, three TAG synthesis-related genes, DGA1, LRO1, and ARE1, were down-regulated successively via the RNA interference technology, and an endogenous TAG lipase encoded by TGL5 was fused with LDP1 and over-expressed to convert TAG into DAG and FFA. Results showed that those engineered R. toruloides strains grew normally under nutrient-rich conditions but notably slower than the parental strain NP11 in the lipid production stage. When cultivated in nitrogen-limited media, engineered strains were able to produce total lipids with improved contents of DAG and FFA by up to two-fold and three-fold, respectively. Further correlation analysis between lipid composition and cell density indicated that the formation of TAG correlated positively with cell growth; however, other lipids including DAG did negatively. This study offered valuable information and strains to engineer R. toruloides for advanced production of fatty acid derivatives.
Effect of chitosan/inorganic nanomaterial scaffolds on bone regeneration and related influencing factors in animal models: A systematic review
Authors: Guo Anjie , Zheng Yi , Zhong Yu , Mo Shuixue , Fang Shanbao
Published: October 2022

Bone tissue engineering (BTE) provides a promising alternative for transplanting. Due to biocompatibility and biodegradability, chitosan-based scaffolds have been extensively studied. In recent years, many inorganic nanomaterials have been utilized to modify the performance of chitosan-based materials. In order to ascertain the impact of chitosan/inorganic nanomaterial scaffolds on bone regeneration and related key factors, this study presents a systematic comparison of various scaffolds in the calvarial critical-sized defect (CSD) model. A total of four electronic databases were searched without publication date or language restrictions up to April 2022. The Animal Research Reporting of In Vivo Experiments 2.0 guidelines (ARRIVE 2.0) were used to assess the quality of the included studies. Moreover, the risk of bias (RoB) was evaluated via the Systematic Review Center for Laboratory Animal Experimentation (SYRCLE) tool. After the screening, 22 studies were selected. None of these studies achieved high quality or had a low RoB. In the available studies, scaffolds reconstructed bone defects in radically different extensions. Several significant factors were identified, including baseline characteristics, physicochemical properties of scaffolds, surgery details, and scanning or reconstruction parameters of micro-computed tomography (micro-CT). Further studies should focus on not only improving the osteogenic performance of the scaffolds but also increasing the credibility of studies through rigorous experimental design and normative reports.
Clinical risk factors and social needs of 30-day readmission among patients with diabetes: A retrospective study of the Deep South
Authors: McDaniel Cassidi C. , Chou Chiahung
Published: October 2022

Introduction

Evidence is needed for 30-day readmission risk factors (clinical factors and social needs) among patients with diabetes in the Deep South. To address this need, our objectives were to identify risk factors associated with 30-day readmissions among this population and determine the added predictive value of considering social needs.

Methods

This retrospective cohort study utilized electronic health records from an urban health system in the Southeastern U.S. The unit of analysis was index hospitalization with a 30-day washout period. The index hospitalizations were preceded by a 6-month pre-index period to capture risk factors (including social needs), and hospitalizations were followed 30 days post-discharge to evaluate all-cause readmissions (1=readmission; 0=no readmission). We performed unadjusted (chi-square and student’s t-test, where applicable) and adjusted analyses (multiple logistic regression) to predict 30-day readmissions.

Results

A total of 26,332 adults were retained in the study population. Eligible patients contributed a total of 42,126 index hospitalizations, and the readmission rate was 15.21%. Risk factors associated with 30-day readmissions included demographics (e.g., age, race/ethnicity, insurance), characteristics of hospitalizations (e.g., admission type, discharge status, length of stay), labs and vitals (e.g., highest and lowest blood glucose measurements, systolic and diastolic blood pressure), co-existing chronic conditions, and preadmission antihyperglycemic medication use. In univariate analyses of social needs, activities of daily living (p<0.001), alcohol use (p<0.001), substance use (p=0.002), smoking/tobacco use (p<0.001), employment status (p<0.001), housing stability (p<0.001), and social support (p=0.043) were significantly associated with readmission status. In the sensitivity analysis, former alcohol use was significantly associated with higher odds of readmission compared to no alcohol use [aOR (95% CI): 1.121 (1.008-1.247)].

Conclusions

Clinical assessment of readmission risk in the Deep South should consider patients’ demographics, characteristics of hospitalizations, labs, vitals, co-existing chronic conditions, preadmission antihyperglycemic medication use, and social need (i.e., former alcohol use). Factors associated with readmission risk can help pharmacists and other healthcare providers identify high-risk patient groups for all-cause 30-day readmissions during transitions of care. Further research is needed about the influence of social needs on readmissions among populations with diabetes to understand the potential clinical utility of incorporating social needs into clinical services.
Negative results of bronchoalveolar lavage fluid metagenomic next-generation sequencing in critically ill patients
Authors: Ma Wentao , Zhao Yangchao , Lu Xiaoxiao , Zhang Li , Ma Xiaoxu , Gao Jing , Hou Junna , Liu Qiuhong , Zhao Shilong , Yao Mengying , Xing Lihua
Published: October 2022

Objective

Reports on negative results of metagenomic next-generation sequencing (mNGS) are scarce. We aimed to explore the diagnostic value of negative results in bronchoalveolar lavage fluid (BALF) mNGS and how to deal with the negative results in patients with severe respiratory disease.

Methods

A retrospective analysis was performed on patients suspected severe community-acquired pneumonia who were admitted to the respiratory intensive care unit of the First Affiliated Hospital of Zhengzhou University from January 2020 to December 2021. According to the final diagnosis as the reference standard, the negative results of mNGS were divided into a true negative group and a false negative group. For enrolled patients, we recorded their demographic data, imaging results, laboratory results, therapeutic processes, and prognoses.

Results

A total of 21 patients were enrolled in this study, including 16 true negative patients and 5 false negative patients. In the true negative group, interstitial lung diseases were the most and neoplastic diseases were following. In addition to mNGS, 9 patients underwent pathological examination, 7 patients were finally diagnosed by medical history, autoantibodies, and point-of-care (POC) ultrasound. 14 patients eventually discontinued antibiotics, 2 patients underwent antibiotic de-escalation, the average interval time of treatment adjustment was 3.56 ± 2.00 days. In the false negative group, the leading missed pathogen was fungi, followed by tuberculosis bacilli. In contrast to 2 patients underwent pathological examination, 3 patients were confirmed by routine microbiological tests.

Conclusions

Negative results of BALF mNGS can help to rule out infection, but missed diagnoses may also exist. It should be re-evaluated with other clinical informations. Pathological examination or repeated mNGS may be viable options when the diagnosis cannot be confirmed.
Effect of epicardial fat volume on outcomes after left atrial posterior wall isolation in addition to pulmonary vein isolation in patients with persistent atrial fibrillation
Authors: Kim Daehoon , Yu Hee Tae , Kwon Oh-Seok , Kim Tae-Hoon , Uhm Jae-Sun , Joung Boyoung , Lee Moon-Hyoung , Pak Hui-Nam
Published: October 2022

Background

Greater epicardial adipose tissue (EAT) is related to higher recurrences after atrial fibrillation catheter ablation (AFCA). We investigated the effects of posterior wall box isolation (POBI) in conjunction with circumferential pulmonary vein isolation (CPVI) on rhythm outcomes according to varying EAT volumes among patients with persistent atrial fibrillation (PeAF).

Materials and methods

We included 1,187 patients with PeAF undergoing a de novo AFCA including those receiving CPVI alone (n = 687) and those receiving additional POBI (n = 500). The rhythm outcomes at 2 years post-AFCA were compared in subgroups stratified by the EAT volume using propensity overlap weighting.

Results

A reduced EAT volume was linearly associated with more favorable rhythm outcomes for additional POBI than for CPVI alone (P for interaction = 0.002). Among the patients with smaller EAT volumes (≤116.23 mL, the median value, n = 594), additional POBI was associated with a reduced AF recurrence risk as compared to CPVI only [weighted HR (hazard ratio) 0.74, 95% CI (confidence interval) 0.56–0.99]. In contrast, among the remaining 593 patients with greater EAT volumes (>116.23 mL), No difference was observed in the recurrence risk between the additional POBI and CPVI alone groups (weighted HR 1.13, 95% CI 0.84–1.52). Among 205 patients with repeat ablations, the POBI reconnection rate was more frequent in the large EAT group (77.4%) than in the small EAT group (56.7%, P = 0.034).

Conclusion

While PeAF patients with a smaller EAT volume averted AF recurrence by additional POBI after CPVI, no benefit of the POBI was observed in those with a greater EAT volume.
Comparison of two techniques in proximal anastomosis in acute type A aortic dissection
Authors: Fang Changcun , Gao Shan , Ren Xiao , Pang Xinyan , Zhao Xin , Ma Zengshan , Wang Chen , Liu Kai
Published: October 2022

Background

The proximal anastomosis is an important procedure during the acute type A aortic dissection (AAAD) surgery. The conventional method is a double patch sandwich technique with Teflon felt. Adventitial eversion and prosthesis eversion technique as a novel approach has been applied to many patients in our center. Herein, This technique would be introduced, and the perioperative and 1-year follow-up results of the two different anastomosis methods were also evaluated.

Methods

Between December 2017 and May 2021, 143 AAAD patients who underwent total arch replacement (TAR) and frozen elephant trunk (FET) implantation were included in this retrospective study. Patients were divided into the eversion technique group (adventitial eversion and prosthesis eversion technique for proximal anastomosis, n = 64) and the sandwich technique group (n = 79).

Results

The medical records were analyzed and compared between the groups. The mean operation time was 466 ± 73 min in the eversion technique group and 513 ± 81 min in the sandwich technique group (P < 0.001). Compared with the sandwich technique group, the eversion technique group also showed a shorter time on proximal anastomosis (38 ± 12 min vs. 58 ± 20 min, P < 0.001), cardiopulmonary bypass (195 ± 26 vs. 211 ± 40 min, P = 0.003), and aortic cross-clamp (120 ± 23 min vs. 134 ± 27 min, P = 0.002). Furthermore, a decreased proportion of >600 ml fresh frozen plasmas transfusion was observed in eversion technique group (10.9% vs. 34.2%, P = 0.002). No statistical differences were found in the postoperative morbidities and 1-year follow-up outcomes.

Conclusion

Proximal anastomosis with adventitial eversion and prosthesis eversion technique is a promising surgical option for AAAD patients, with favorable perioperative and 1-year follow-up results.
Single-cell RNA-sequencing analysis of aortic valve interstitial cells demonstrates the regulation of integrin signaling by nitric oxide
Authors: Majumdar Uddalak , Choudhury Talita Z. , Manivannan Sathiyanarayanan , Ueyama Yukie , Basu Madhumita , Garg Vidu
Published: October 2022

Calcific aortic valve disease (CAVD) is an increasingly prevalent condition among the elderly population that is associated with significant morbidity and mortality. Insufficient understanding of the underlying disease mechanisms has hindered the development of pharmacologic therapies for CAVD. Recently, we described nitric oxide (NO) mediated S-nitrosylation as a novel mechanism for preventing the calcific process. We demonstrated that NO donor or an S-nitrosylating agent, S-nitrosoglutathione (GSNO), inhibits spontaneous calcification in porcine aortic valve interstitial cells (pAVICs) and this was supported by single-cell RNA sequencing (scRNAseq) that demonstrated NO donor and GSNO inhibited myofibroblast activation of pAVICs. Here, we investigated novel signaling pathways that are critical for the calcification of pAVICs that are altered by NO and GSNO by performing an in-depth analysis of the scRNA-seq dataset. Transcriptomic analysis revealed 1,247 differentially expressed genes in pAVICs after NO donor or GSNO treatment compared to untreated cells. Pathway-based analysis of the differentially expressed genes revealed an overrepresentation of the integrin signaling pathway, along with the Rho GTPase, Wnt, TGF-β, and p53 signaling pathways. We demonstrate that ITGA8 and VCL, two of the identified genes from the integrin signaling pathway, which are known to regulate cell-extracellular matrix (ECM) communication and focal adhesion, were upregulated in both in vitro and in vivo calcific conditions. Reduced expression of these genes after treatment with NO donor suggests that NO inhibits calcification by targeting myofibroblast adhesion and ECM remodeling. In addition, withdrawal of NO donor after 3 days of exposure revealed that NO-mediated transcriptional and translational regulation is a transient event and requires continuous NO exposure to inhibit calcification. Overall, our data suggest that NO and S-nitrosylation regulate the integrin signaling pathway to maintain healthy cell-ECM interaction and prevent CAVD.
Comparison between thoracic low-dose computed tomography and conventional-dose computed tomography in evaluating anemia: A preliminary study in a Chinese screening cohort
Authors: Zhang Jianing , Wu Minghao , Huang Jinchao , Li Shixia , Ye Zhaoxiang
Published: October 2022

Purpose

To investigate and evaluate the value of thoracic low dose computed tomography (LDCT) scan in the diagnosis of anemia.

Materials and methods

661 patients who received thoracic computed tomography (CT) examination and underwent a peripheral blood examination were retrospectively included. 341 patients underwent conventional dose CT (CDCT), and 320 patients underwent LDCT. Regions of interest (ROI) were placed on the left ventricular cavity (LV), descending aorta (DAo), and interventricular septum (IVS). The corresponding CT attenuation was measured, and the CT attenuation difference between LV and IVS (IVS-LV) and between DAo and IVS (IVS-DAo) was calculated, respectively. One-way analysis of variance (ANOVA) and linear regression were performed to analyze the relationship between these indicators and Hb levels. The receiver operating characteristic (ROC) curve was used to evaluate prediction performance.

Results

Both attenuation on LDCT and CDCT showed significant differences between the healthy group and the anemic group (P < 0.05). In the LDCT group, the LV and DAo were more relevant with the hemoglobin (Hb) level (correlation coefficient 0.618 and 0.602) than other indicators, with AUCs of 0.815 (95% CI: 0.763–0.868) and 0.803 (95% CI: 0.747–0.859), respectively. The linear regression formulas for Hb level with the LV and DAo were 19.14 + 0.15 × HU [95% CI: (16.52, 21.75) + (0.12, 0.17) × HU] and 19.46 + 0.16 × HU [95% CI: (16.55, 22.36) + (0.13, 0.18) × HU], respectively. Youden’s index indicated that 37.5 HU and 38.5 HU were the best thresholds to diagnose anemia for LV and DAo, respectively. In the CDCT group, the LV and IVS-LV got obviously higher correlation coefficients (0.813 and 0.812), with AUCs of 0.831 (95% CI: 0.786–0.877) and 0.851 (95% CI: 0.808–0.894), respectively. The optimal thresholds for LV and IVS-LV were 40.5 HU and 9.5 HU, respectively.

Conclusion

In LDCT examinations, an approximation of Hb level and detecting of anemia can be conducted based on simple attenuation measurements.
Improving students’ ability in learning mathematics by using the science, technology, engineering, and mathematics (STEM) approach
Authors: Ilyas Muhammad , Meiyani Eliza , Ma’rufi Ma’rufi , Kaewhanam Phimlikid
Published: October 2022

The science, technology, engineering, and mathematics (STEM) approach is a leading and important learning approach to analyze thinking ability and learning motivation. Accordingly, this study attempts to elaborate a STEM approach to analyze the critical thinking ability and motivation of high school students in Indonesia, especially in Palopo City, South Sulawesi, Indonesia. The current research applied pre-experimental treatment on research objects involving a group of experimental classes. Pre-experimental was used in testing the STEM approach in an experimental class with a one-group pretest–posttest design with 176 students divided into five classes. The results show: (1) improvement in students’ critical thinking ability indicated by an average pretest score of 13.90 and posttest score of 70.67; (2) an increase in student learning motivation shown by an average of 71.57–80.83. The analysis results show an increase in students’ critical thinking ability and learning motivation after applying the STEM approach. Conclusively, STEM functions as one of the practical learning methods for improving students’ critical thinking skills and learning motivation.
The role of microRNAs in erectile dysfunction: From pathogenesis to therapeutic potential
Authors: Song Jingyu , Wang Jiaxin , Liu Kang , Xu Wenchao , Sun Taotao , Liu Jihong
Published: October 2022

Erectile dysfunction (ED) is a common male sexual dysfunction disease, and it was predicted that the number of ED patients worldwide will reach 322 million by 2025. However, the pathogenesis of ED is complex and the current treatment options are still limited, so it is urgent to explore new treatment strategies. Recent studies have shown that microRNAs (miRNAs) play an important role in ED, and these single-stranded non-coding small RNA molecules are involved in key pathophysiological processes in the occurrence and development of ED. Therefore, miRNAs have remarkable potential as therapeutic targets in ED. Here, this review introduces the physiological basis of erectile function and the pathophysiological changes in ED and summarizes the current knowledge on the expression, biological functions, and molecular mechanisms of miRNAs in ED, especially the potential of miRNA-targeted therapies to improve ED. This review will provide a comprehensive view of the role of miRNAs in the pathogenesis of ED and the potential value of miRNAs in the treatment of ED.
Estimates of global research productivity in primary ovarian insufficiency from 2000 to 2021: Bibliometric analysis
Authors: Zhang Xudong , Lu Yimeng , Wu Shanshan , Zhao Xinyang , Li Shuyu , Zhang Siwen , Tan Jichun
Published: October 2022

Background

Primary ovarian insufficiency (POI) is a heterogeneous disease with diverse clinical phenotypes and etiologies, which is defined as ovarian dysfunction under the age of 40 years. The global prevalence of POI is approximately about 1.1%, and it severely affects female fertility. Nevertheless, bibliometric analysis in this field is extremely limited. We aimed to visualize the research hotspots and trends of POI using bibliometric analysis and tried to predict the future development of this field.

Methods

The original articles regarding POI were culled from the Web of Science Core Collection. Countries, institutions, journals, authors, and keywords in this field were visually analyzed by employing CiteSpace software and Microsoft Excel 2021 software.

Results

A total of 2,999 publications were included for further bibliometric analysis after screening the titles and abstracts stringently. The number of literature regarding POI significantly increased yearly. These publications come from 78 countries. The USA was dominant in the field of POI in terms of the number of publications (865), average citations per item (57.36), and h-index (112). The Institut National De La Sante Et De La Recherche Medicale Inserm is the most high-yield institution in this field with 351 publications. Fertility and Sterility ranked first with the highest number of publications (152), followed by Human Reproduction (138). According to the keyword cluster analysis from 2000 to 2021, the eight keyword clusters encountered frequently were apoptosis, osteoporosis, fertility preservation, mutation, fragile x syndrome, adrenal insufficiency, DNA repair, ovarian reserve. Keyword citation burst analysis revealed that whole-exome sequencing, ovarian tissue cryopreservation, and DNA repair had a citation burst until 2021.

Conclusions

Great progress has been made in POI research over the past 20 years, which is widely researched but unevenly developed in the world. In terms of influence, the United States may be in the lead. The research hotspots in POI are mainly pathogenesis and treatment, including genetic mutation, hormone therapy, fertility preservation, and stem cell transplantation.
SustainGraph: A knowledge graph for tracking the progress and the interlinking among the sustainable development goals’ targets
Authors: Fotopoulou Eleni , Mandilara Ioanna , Zafeiropoulos Anastasios , Laspidou Chrysi , Adamos Giannis , Koundouri Phoebe , Papavassiliou Symeon
Published: October 2022

The development of solutions to manage or mitigate climate change impacts is very challenging, given the complexity and dynamicity of the socio-environmental and socio-ecological systems that have to be modeled and analyzed, and the need to include qualitative variables that are not easily quantifiable. The existence of qualitative, interoperable and well-interlinked data is considered a requirement rather than a desire in order to support this objective, since scientists from different disciplines will have no option but to collaborate and co-design solutions, overcoming barriers related to the semantic misalignment of the plethora of available data, the existence of multiple data silos that cannot be easily and jointly processed, and the lack of data quality in many of the produced datasets. In the current work, we present the SustainGraph, as a Knowledge Graph that is developed to track information related to the progress towards the achievement of targets defined in the United Nations Sustainable Development Goals (SDGs) at national and regional levels. The SustainGraph aims to act as a unified source of knowledge around information related to the SDGs, by taking advantage of the power provided by the development of graph databases and the exploitation of Machine Learning (ML) techniques for data population, knowledge production and analysis. The main concepts represented in the SustainGraph are detailed, while indicative usage scenarios are provided. A set of opportunities to take advantage of the SustainGraph and open research areas are identified and presented.
Higher expected returns for investors in the energy sector in Europe using an ESG strategy
Authors: Wanday Julia , Ajour El Zein Samer
Published: October 2022

The energy sector is transforming as new regulations are set in place to take into account the environmental and social factors as well as corporate governance initiatives which can be integrated within organisations. Companies are pushing towards having better environmental, social and governance (ESG) scores as it impacts shareholders, investors, employees, customers amongst many others. The methodology used in this paper is quantitative and includes an analysis of the financial performance of publicly listed companies using return on equity, return on assets, return on sales, return on investment and also used the SARIMA (seasonal autoregressive integrated moving average) model to forecast revenues for the companies included in the research. The aim of this study is to investigate the impact of ESG activities within companies and how it affects investor returns. Considering regional and sectoral effects an observation of a positive relationship between ESG and investor returns is identified.
Evaluating earthworms as candidates for remediating pesticide contaminated agricultural soil: A review
Authors: Mishra C. S. K. , Samal Suryasikha , Samal Rashmi Rekha
Published: October 2022

Alterations of soil characteristics that result in reduction in ecosystem services invariably cause soil quality degradation. Such changes could be caused due to a variety of stressors, which might be physical, chemical, or biological and come from both anthropogenic and natural causes. Out of the wide variety of soil pollutants, agrochemicals contaminate soil biota the most. Numerous research’ findings have confirmed that soil has been the most preferred site for the disposal of xenobiotics and therefore is likely to be the source of contamination for other natural resources like ground and surface waters. The ecological risk associated with contaminated soils depends on many physicochemical and biological processes that govern the transport and transformation of pesticides. Nevertheless, the persistence of pesticides in soil is a serious threat to both below and above ground organisms which play key roles in sustaining soil functions. One of the viable methods to decontaminate soil is by utilizing living soil biota selectively. This process called. Bioremediation has traditionally been employed to remove chemical residues from soil or to lessen their toxicity levels. Although microbes have been extensively used for bioremediation, chemical breakdown and remediation are significantly aided by certain dominant soil fauna, such as earthworms. Since they modify soil quality, earthworms are regarded as soil engineers. Earthworms can participate in the degradation of pesticide residues, either directly through the release of detoxifying enzymes in their gut or indirectly through their positive influence on microbial populations which could degrade pesticides. The earthworm supported pesticide degradation is largely confined to the gut microenvironment and the soil processed by the worms. The impact of earthworm species on pesticide degradation is widely variable which could be related to their feeding habits and microhabitats. Molecular docking studies have provided evidence in support of binding of organic molecules with agrochemicals. High level of organic matter in soil is expected to increase the binding of hydrophobic pesticides to organic ligands with consequent reduction in their bioavailability to microorganisms and increasing their persistence. Activities of earthworms is likely to induce growth of aerobic microbes capable of pesticide degradation. Among the various earthworm species, Lumbricus terrestris, Perionyx excavatus and Metaphire posthuma have shown promising results as remediating agents of pesticides contaminating farm soils. The present article focuses on the remediation process of hazardous pesticide polluted soil using biological agent like earthworm. This approach may be both efficient and environmentally beneficial.
The importance of wild resources as a reflection of the resilience and changing nature of early agricultural systems in East Asia and Europe
Authors: Stevens Chris J. , Crema Enrico R. , Shoda Shinya
Published: October 2022

We examine the changing importance of wild starch rich plant staples, predominantly tree nuts, in early agricultural societies in East Asia and Europe, focusing on Korea, Japan, and Britain. A comparative review highlights variations in the importance of wild plant staples compared to domesticated crops. The Korean Middle to Late Chulmun periods (c. 3,500–1,500 BC) was characterized by a high reliance on nuts alongside millet. This declines with the transition to rice agriculture, but remains significant during the Mumun period (c. 1,500–300 BC). In Japan, the arrival of rice and millets in the Yayoi Period (c. 1,000 BC−250 AD) saw continued evidence for high levels of reliance on wild resources, which declines only in the Kofun and early historical periods. In Early Neolithic Britain (c. 4,000–3,300 BC) cereal agriculture is accompanied by high evidence for wild plant foods. But during the Middle to Late Neolithic (3,300–c. 2,400/2,200 BC) cereals were abandoned on the mainland with hazelnuts becoming a prominent plant staple. Agriculture returned in the second half of the 3rd millennium BC, followed by a strong decline in wild plant food use during the Middle to Late Bronze Age (1,700–700 BC). Such patterns have previously been attributed to the slow adoption of farming by indigenous peoples, with a continued reliance on wild resources. In light of evidence demonstrating that the dispersal of agriculture was largely driven by a mixture of demic-diffusion and introgression of hunter-gatherers into agricultural groups, a reinterpretation of the role of wild foods is needed. It is argued that the relative importance of wild plant staples provides an indicator of the stability and dependability of agricultural and social systems. A heavy reliance on wild foods in early agricultural societies is tied to the slow adaptation of domesticated crops to new environments, where agricultural and social landscapes are yet to be firmly established, and social systems that could mitigate for poor harvests and storage were often absent. The retained lengthy persistence of wild plant staples in East Asian subsistence systems compared to the British Isles likely reflects differences in the ecological and labor demands for rice compared to Western Asiatic cereals.
Increased levels of anti-PfCSP antibodies in post-pubertal females versus males immunized with PfSPZ Vaccine does not translate into increased protective efficacy
Authors: KC Natasha , Church L. W. Preston , Riyahi Pouria , Chakravarty Sumana , Seder Robert A. , Epstein Judith E. , Lyke Kirsten E. , Mordmüller Benjamin , Kremsner Peter G. , Sissoko Mahamadou S. , Healy Sara , Duffy Patrick E. , Jongo Said A. , Nchama Vicente Urbano Nsue Ndong , Abdulla Salim , Mpina Maxmillian , Sirima Sodiomon B. , Laurens Matthew B. , Steinhardt Laura C. , Oneko Martina , Li MingLin , Murshedkar Tooba , Billingsley Peter F. , Sim B. Kim Lee , Richie Thomas L. , Hoffman Stephen L.
Published: October 2022

Background

While prior research has shown differences in the risk of malaria infection and sickness between males and females, little is known about sex differences in vaccine-induced immunity to malaria. Identifying such differences could elucidate important aspects of malaria biology and facilitate development of improved approaches to malaria vaccination.

Methods

Using a standardized enzyme-linked immunosorbent assay, IgG antibodies to the major surface protein on Plasmodium falciparum (Pf) sporozoites (SPZ), the Pf circumsporozoite protein (PfCSP), were measured before and two weeks after administration of a PfSPZ-based malaria vaccine (PfSPZ Vaccine) to 5-month to 61-year-olds in 11 clinical trials in Germany, the US and five countries in Africa, to determine if there were differences in vaccine elicited antibody response between males and females and if these differences were associated with differential protection against naturally transmitted Pf malaria (Africa) or controlled human malaria infection (Germany, the US and Africa).

Results

Females ≥ 11 years of age made significantly higher levels of antibodies to PfCSP than did males in most trials, while there was no indication of such differences in infants or children. Although adult females had higher levels of antibodies, there was no evidence of improved protection compared to males. In 2 of the 7 trials with sufficient data, protected males had significantly higher levels of antibodies than unprotected males, and in 3 other trials protected females had higher levels of antibodies than did unprotected females.

Conclusion

Immunization with PfSPZ Vaccine induced higher levels of antibodies in post-pubertal females but showed equivalent protection in males and females. We conclude that the increased antibody levels in post-pubertal females did not contribute substantially to improved protection. We hypothesize that while antibodies to PfCSP (and PfSPZ) may potentially contribute directly to protection, they primarily correlate with other, potentially protective immune mechanisms, such as antibody dependent and antibody independent cellular responses in the liver.
Immunotherapy for bilateral multiple ground glass opacities: An exploratory study for synchronous multiple primary lung cancer
Authors: Xu Lin , Shi Meiqi , Wang Siwei , Li Ming , Yin Wenda , Zhang Jingyuan , Zhu Jun , Jiang Feng , Xia Wenjia , Qiu Ninglei , Zhang Zhi , Huang Jianfeng , Ma Zhifei , Meng Fanchen , Zhu Hongyu , Dong Guozhang , Wang Jie , Yin Rong
Published: October 2022

Background

Bilateral multiple ground glass opacities (GGOs) are observed in quite a part of patients with early-stage lung adenocarcinoma. For this so-called synchronous multiple primary lung cancer (sMPLC), targeting immune checkpoint is a favorable option in addition to surgical resection. The purpose of this study is to reveal the safety and efficacy of performing immune checkpoint inhibitors (ICIs) on patients with sMPLC and to explore the biomarkers of the efficacy.

Methods

A total of 21 patients with sMPLC were enrolled and all included cases were pathologically confirmed adenocarcinoma after conducting surgical treatment for unilateral GGOs. ICIs of Sintilimab were then used to target programmed death 1 (200mg i.v., Q3W) for up to 10 cycles. Seven patients of them received the other surgery for contralateral GGOs, and multiomics assessments, including neoantigens, somatic mutations, and methylated loci, were further performed to investigate potential biomarkers.

Results

Grade 1 or 2 treatment-related adverse events (AEs) occurred in most of the patients (12/21, 57.1%), and one subject withdrawn for grade 3 AEs. For the seven patients underwent twice surgeries, twelve and thirteen GGOs were achieved before and after the use of ICIs separately, and a favorable efficacy was observed among six lesions after immunotherapy (> 50% pathologic tumor regression). Tumor infiltration T-cell and B-cell were further shown to be associated with the biological activity of ICIs. According to mechanism-based multiomics analyses, MUC19- and PCDHB5- mutations were indicated to correlate with a favorable prognosis of sMPLC underwent immunotherapy, and our results suggested that immunogenetic mutation and associated promoter methylation could provide a quantitative explanation for the pathologic response of GGOs.

Conclusion

Our study provides evidence that the use of ICIs contributed favorable efficacy and safety to patients with sMPLC. Immune infiltration and immunogenic biomarkers are revealed to be implications of performing ICIs on sMPLC. These preliminary findings exhibit the prospects in performing neoadjuvant or adjuvant immunotherapies on patients with sMPLC.

Clinical Trial Registration

https://www.chictr.org.cn/showproj.aspx?proj=36878, identifier ChiCTR1900022159.
CD3e-immunotoxin spares CD62Llo Tregs and reshapes organ-specific T-cell composition by preferentially depleting CD3ehi T cells
Authors: Kim Shihyoung , Shukla Rajni Kant , Yu Hannah , Baek Alice , Cressman Sophie G. , Golconda Sarah , Lee Ga-Eun , Choi Hyewon , Reneau John C. , Wang Zhirui , Huang Christene A. , Liyanage Namal P. M. , Kim Sanggu
Published: October 2022

CD3-epsilon(CD3e) immunotoxins (IT), a promising precision reagent for various clinical conditions requiring effective depletion of T cells, often shows limited treatment efficacy for largely unknown reasons. Tissue-resident T cells that persist in peripheral tissues have been shown to play pivotal roles in local and systemic immunity, as well as transplant rejection, autoimmunity and cancers. The impact of CD3e-IT treatment on these local cells, however, remains poorly understood. Here, using a new murine testing model, we demonstrate a substantial enrichment of tissue-resident Foxp3+ Tregs following CD3e-IT treatment. Differential surface expression of CD3e among T-cell subsets appears to be a main driver of Treg enrichment in CD3e-IT treatment. The surviving Tregs in CD3e-IT-treated mice were mostly the CD3edimCD62Llo effector phenotype, but the levels of this phenotype markedly varied among different lymphoid and nonlymphoid organs. We also found notable variations in surface CD3e levels among tissue-resident T cells of different organs, and these variations drive CD3e-IT to uniquely reshape T-cell compositions in local organs. The functions of organs and anatomic locations (lymph nodes) also affected the efficacy of CD3e-IT. The multi-organ pharmacodynamics of CD3e-IT and potential treatment resistance mechanisms identified in this study may generate new opportunities to further improve this promising treatment.
The clinical significance of allergen-specific IgG4 in allergic diseases
Authors: Qin Lu , Tang Lan-Fang , Cheng Lei , Wang Hui-Ying
Published: October 2022

IgG4 is a subclass of IgG antibody with a unique molecular feature of (Fragment antigen- binding) Fab-arm exchange, allowingbispecific antigen binding in amono-valent manner. With low binding affinity to C1q and Fcγreceptors, IgG4 is incapable of forming immune complexes and activating the complement pathway, exhibiting a non-inflammatory feature. IgG4 is produced similarly to IgE and is consideredamodified reaction to IgE class-switching response under certain conditions. It could also counteract IgE-activated inflammation. However, the clinical significance of IgG4 in allergic diseases is complex and controversial. Three viewpoints have been suggested to describe the role of IgG4. IgG4 can act as a tolerance–inducer to play a protective role under repeated and rapid incremental dosing of allergen exposure in allergen immunotherapy (AIT), supported by allergies in cat raisers and venom desensitization in beekeepers. Another viewpoint accepted by mainstream specialists and guidelines of Food Allergy and Management in different countries points out that food-specific IgG4 is a bystander in food allergy and should not be used as a diagnostic tool in clinical work. However, eosinophilic esophagitis (EoE) investigation revealed a direct clinical relevance between physiopathology and serum IgG4 in cow milk and wheat. These factors indicate that allergen-specific IgG4 plays a multifaceted role in allergic diseases that is protective or pathogenic depending on different allergens or exposure conditions.
Innate lymphoid cells: More than just immune cells
Authors: Xiong Le , Nutt Stephen L. , Seillet Cyril
Published: October 2022

Since their discovery, innate lymphoid cells (ILCs) have been described as the innate counterpart of the T cells. Indeed, ILCs and T cells share many features including their common progenitors, transcriptional regulation, and effector cytokine secretion. Several studies have shown complementary and redundant roles for ILCs and T cells, leaving open questions regarding why these cells would have been evolutionarily conserved. It has become apparent in the last decade that ILCs, and rare immune cells more generally, that reside in non-lymphoid tissue have non-canonical functions for immune cells that contribute to tissue homeostasis and function. Viewed through this lens, ILCs would not be just the innate counterpart of T cells, but instead act as a link between sensory cells that monitor any changes in the environment that are not necessarily pathogenic and instruct effector cells that act to maintain body homeostasis. As these non-canonical functions of immune cells are operating in absence of pathogenic signals, it opens great avenues of research for immunologists that they now need to identify the physiological cues that regulate these cells and how the process confers a finer level of control and a greater flexibility that enables the organism to adapt to changing environmental conditions. In the review, we highlight how ILCs participate in the physiologic function of the tissue in which they reside and how physiological cues, in particular neural inputs control their homeostatic activity.
Functional antibodies against G-protein coupled receptors in Beagle dogs infected with two different strains of Trypanosoma cruzi
Authors: Wallukat Gerd , Botoni Fernando Antônio , Rocha Manoel Otávio da Costa , Louise Vitória , Müller Johannes , Talvani Andre
Published: October 2022

The interaction of the anti-beta1-adrenergic receptor autoantibodies (β1ARAb) and the anti-muscarinic M2 receptor autoantibodies (M2RAb) with cardiac neurotransmitter receptors were identified in human chronic Chagas cardiomyopathy (CCC) related to the ECG and dysautonomia disturbances. Dogs are considered gold model to the study of Trypanosoma cruzi infection due the clinical similarities with CCC. This study aims to evaluate whether anti-β1ARAb, anti-β2ARAb, and anti-muscarinic M2RAb are generated in Beagle dogs infected by T. cruzi using Y and Berenice-78 strains of T. cruzi. Animals were infected with 4.0 x 103 bloodstream trypomastigotes/kg of body weight and, after 25 months of infection, blood sample was collected, and serum stored at -80°C. Dog serum was treated by ammonium sulphate precipitation and the IgG antibodies isolated and added to the beating neonatal rats’ cardiomyocytes. All T. cruzi-infected dogs developed agonistic β1ARAb, β2ARAb, and M2RAb. Animals infected by Berenice strain presented less β2ARAb and M2RAb activities than dogs infected by Y strain of the parasite. In cardiomyocytes culture, the antibodies recognized an epitope on the second extracellular loop of the receptors which were similar to findings in human Chagas disease. There was no detection of antibody against G protein-coupled receptor in serum from uninfected dogs. In conclusion, both Y and Berenice-78 strains of T. cruzi induced dog antibodies, whose targets located in the second extracellular loop of the adrenergic and muscarinic receptors were similar to those observed in individuals with CCC. Therefore, our findings highlight dogs as a promisor model to investigate pathogenic roles of functional Ab against G-protein coupled receptors.
Association between the side effect induced by COVID-19 vaccines and the immune regulatory gene polymorphism
Authors: Chen Ding-Ping , Wen Ying-Hao , Lin Wei-Tzu , Hsu Fang-Ping
Published: October 2022

People often worry about the side effects after vaccination, reducing the willingness to vaccinate. Thus, we tried to find out the risk of single nucleotide polymorphism (SNP) vaccines to improve the willingness and confidence in vaccination. Allergic and inflammatory reactions are the common vaccine side effects caused by immune system overreaction. In addition, a previous study showed significantly higher frequency of febrile reactions to measles vaccines in American Indians than in Caucasian children, indicating that the side effects varied in accordance with genetic polymorphisms in individuals. Thus, SNPs of immune regulatory genes, cytotoxic T-lymphocyte-associated protein 4 (CTLA4), CD28, tumor necrosis factor ligand superfamily member 4 (TNFSF4) and programmed cell death protein 1 (PDCD1) were included in this study to analyze their association with vaccine side effects. Moreover, 61 healthy participants were asked on the number of doses they received, the brand of the vaccine, and the side effects they suffered. We found that several SNPs were associated with side effects after the first or second dose of mRNA or adenoviral vector vaccines. Furthermore, these SNPs were associated with several autoimmune diseases and cancer types; thus, they played an important role in immune regulation. Moreover, rs3181096 and rs3181098 of CD28, rs733618 and rs3087243 of CTLA, and rs1234314 of TNFSF4 were associated with mild vaccine side effects induced by mRNA and adenoviral vector vaccines, which would play a potential role in vaccine-induced immune responses and may further lead to fatal side effects. These results could serve as a basis for investigating the mechanism of vaccine side effects. Furthermore, it was hoped that these results would address public concerns about the side effects of the COVID-19 vaccination. In clinical application, a rapid screening test can be performed to assess the risk of vaccine side effects before vaccination and provide immediate treatment.
Social enrichment affects fish growth and aggression depending on fish species: Applications for aquaculture
Authors: Zhang Zonghang , Fu Yiqiu , Zhao Hancheng , Zhang Xiumei
Published: October 2022

Growth performance and aggressive behavior are important measures in fish aquaculture. So, from the perspectives of food production and fish welfare, it is always valuable to increase growth rate and reduce fish aggression efficiently. Physical enrichment has been verified to be a promising method to improve fish welfare. But there is very scarce knowledge about social enrichment, which is an important category of environmental enrichment. In the wild, several fish species often inhabit the same habitat, inevitably experiencing social interactions with each other. From the perspective of nature-based welfare, such social interactions are essential for fish ontogenesis, and deprivation of this social environment may damage fish welfare. Here, we focused on two typical territorial fish species, black rockfish (Sebastes schlegelii) and fat greenling (Hexagrammos otakii), which are often found to inhabit the same area in the wild, in contrast, traditional fish farms simultaneously rear them with the monoculture mode. And we explored the effects of social enrichment (through introducing different numbers of two fishes into the same environment) on their growth and aggression. The results showed that introducing rockfish as a stimulus significantly increased the growth performance of greenling (especially the medium and high enrichment amounts), but social enrichment did not present such effects on the growth of rockfish. Proper social enrichment also significantly decreased the intraspecies aggression both among rockfish and among greenling. Moreover, greenling expressed significantly more aggressive behavior toward rockfish (i.e., the interspecies aggression from greenling toward rockfish) than in reverse. Finally, the average distribution proportion in central areas and standard metabolic rate of greenling were significantly higher than those of rockfish. These results suggest that proper social enrichment is an effective method to decrease aggression and increase growth of the fat greenling, but this improvement is accompanied by a compromised rockfish welfare. This study will promote the application of environmental enrichment strategy on improving the welfare of specific fish species and provide fundamental information for reducing fish aggression and improving fish growth in aquaculture. Further research is needed to optimize the combinations of fish species for practical applications in aquaculture.