bluuebunny/crossref_metadata_2025 huggingface dataset:
ASPECTOS DE SEQUÊNCIAS INJUNTIVAS EM TEXTO DE INSTRUÇÃO AO SÓSIA DO BRASIL E DA FRANÇA
Authors: Modolo Soelene de Fátima Brovoski , Muniz-Oliveira Siderlene
Published: December 2021

Este artigo objetiva apresentar os resultados de uma análise de aspectos do plano global e dos tipos de sequências de dois textos pertencentes ao gênero - e método - instrução ao sósia, desenvolvido pela Clínica da Atividade (CLOT, 2010). Para isso, seguimos pressupostos do Interacionismo Sociodiscursivo. Como resultados, identificamos divergências quanto ao plano global decorrentes dos contextos de produção dos textos, similaridades nos tipos de sequências e ocorrência de alguns verbos nas sequências injuntivas, além do imperativo e do infinitivo, o que indica a possibilidade de variações nas propriedades de uma sequência a depender do surgimento de novos gêneros, a exemplo da instrução ao sósia.
Across-Species Pose Estimation in Poultry Based on Images Using Deep Learning
Authors: Doornweerd Jan Erik , Kootstra Gert , Veerkamp Roel F. , Ellen Esther D. , van der Eijk Jerine A. J. , van de Straat Thijs , Bouwman Aniek C.
Published: December 2021

Animal pose-estimation networks enable automated estimation of key body points in images or videos. This enables animal breeders to collect pose information repeatedly on a large number of animals. However, the success of pose-estimation networks depends in part on the availability of data to learn the representation of key body points. Especially with animals, data collection is not always easy, and data annotation is laborious and time-consuming. The available data is therefore often limited, but data from other species might be useful, either by itself or in combination with the target species. In this study, the across-species performance of animal pose-estimation networks and the performance of an animal pose-estimation network trained on multi-species data (turkeys and broilers) were investigated. Broilers and turkeys were video recorded during a walkway test representative of the situation in practice. Two single-species and one multi-species model were trained by using DeepLabCut and tested on two single-species test sets. Overall, the within-species models outperformed the multi-species model, and the models applied across species, as shown by a lower raw pixel error, normalized pixel error, and higher percentage of keypoints remaining (PKR). The multi-species model had slightly higher errors with a lower PKR than the within-species models but had less than half the number of annotated frames available from each species. Compared to the single-species broiler model, the multi-species model achieved lower errors for the head, left foot, and right knee keypoints, although with a lower PKR. Across species, keypoint predictions resulted in high errors and low to moderate PKRs and are unlikely to be of direct use for pose and gait assessments. A multi-species model may reduce annotation needs without a large impact on performance for pose assessment, however, with the recommendation to only be used if the species are comparable. If a single-species model exists it could be used as a pre-trained model for training a new model, and possibly require a limited amount of new data. Future studies should investigate the accuracy needed for pose and gait assessments and estimate genetic parameters for the new phenotypes before pose-estimation networks can be applied in practice.
Function and Mechanism of RGD in Bone and Cartilage Tissue Engineering
Authors: Yang Meng , Zhang Zheng-Chu , Liu Yan , Chen You-Rong , Deng Rong-Hui , Zhang Zi-Ning , Yu Jia-Kuo , Yuan Fu-Zhen
Published: December 2021

Bone and cartilage injury is common, tissue engineered scaffolds are potential means to repair. Because most of the scaffold materials used in bone and cartilage tissue engineering are bio-inert, it is necessary to increase the cellular adhesion ability of during tissue engineering reconstruction. The Arginine - Glycine - Aspartic acid (Arg-Gly-Asp, RGD) peptide family is considered as a specific recognition site for the integrin receptors. Integrin receptors are key regulators of cell-cell and cell-extracellular microenvironment communication. Therefore, the RGD polypeptide families are considered as suitable candidates for treatment of a variety of diseases and for the regeneration of various tissues and organs. Many scaffold material for tissue engineering and has been approved by US Food and Drug Administration (FDA) for human using. The application of RGD peptides in bone and cartilage tissue engineering was reported seldom. Only a few reviews have summarized the applications of RGD peptide with alloy, bone cements, and PCL in bone tissue engineering. Herein, we summarize the application progress of RGD in bone and cartilage tissue engineering, discuss the effects of structure, sequence, concentration, mechanical stimulation, physicochemical stimulation, and time stimulation of RGD peptide on cells differentiation, and introduce the mechanism of RGD peptide through integrin in the field of bone and cartilage tissue engineering.
Levulinic Acid-Inducible and Tunable Gene Expression System for Methylorubrum extorquens
Authors: Sathesh-Prabu Chandran , Ryu Young Shin , Lee Sung Kuk
Published: December 2021

Methylorubrum extorquens AM1 is an efficient platform strain possessing biotechnological potential in formate- and methanol-based single carbon (C1) bioeconomy. Constitutive expression or costly chemical-inducible expression systems are not always desirable. Here, several glucose-, xylose-, and levulinic acid (LA)-inducible promoter systems were assessed for the induction of green fluorescent protein (GFP) as a reporter protein. Among them, the LA-inducible gene expression system (HpdR/PhpdH) showed a strong expression of GFP (51-fold) compared to the control. The system was induced even at a low concentration of LA (0.1 mM). The fluorescence intensity increased with increasing concentrations of LA up to 20 mM. The system was tunable and tightly controlled with meager basal expression. The maximum GFP yield obtained using the system was 42 mg/g biomass, representing 10% of the total protein content. The efficiency of the proposed system was nearly equivalent (90%–100%) to that of the widely used strong promoters such as PmxaF and PL/O4. The HpdR/PhpdH system worked equally efficiently in five different strains of M. extorquens. LA is a low-cost, renewable, and sustainable platform chemical that can be used to generate a wide range of products. Hence, the reported system in potent strains of M. extorquens is highly beneficial in the C1-biorefinery industry to produce value-added products and bulk chemicals.
Association of IL33, IL1RL1, IL1RAP Polymorphisms and Asthma in Chinese Han Children
Authors: Wu Maolan , Zheng Xiangrong , Huang Juan , Hu Xiaolei
Published: December 2021

Background: Genome-wide association studies have identified interleukin 33 (IL33), interleukin 1 receptor-like 1 (IL1RL1), interleukin 1 receptor accessory protein (IL1RAP) as asthma susceptibility loci in Europeans. IL33, IL1RL1, and IL1RAP constitute a ligand-receptor complex.

Objective: We analyzed associations of asthma susceptibility, eosinophilic airway inflammation, and response to inhaled corticosteroid (ICS) with single nucleotide polymorphisms (SNPs) of 3 genes encoding IL33, IL1RL1, and its coreceptor IL1RAP in Chinese Han nationality children.

Methods: A total of 153 non-asthmatic children and 265 asthmatic children who visited the Xiangya Hospital between September 2015 and August 2019 were recruited for this study. Pulmonary function tests, peripheral blood eosinophil counts (PBEC), and fractional exhaled nitric oxide (FeNO) tests were performed before treatment, and 3 months after treatment. Each participant’s DNA was extracted from the peripheral blood, and a Mass ARRAY system was used to genotype the SNPs.

Results: The T allele of rs4742170 in IL33 was associated with a risk of higher FeNO at baseline, and no improvement in FeNO and airway hyperresponsiveness was found after ICS treatment. The A allele of rs10208293 and C allele of rs13424006 in IL1RL1 both were associated with lower susceptibility to asthma and lower FeNO. The TT genotype of rs1420101 and AA genotype of rs4142132 in IL1RL1 were associated with a greater probability of improvement in PBEC after ICS treatment.

Conclusion: IL33-IL1RL1-IL1RAP complex polymorphisms are associated with childhood asthma susceptibility, eosinophilic airway inflammation, and ICS response in Chinese Han children in Hunan. We speculate that IL33-IL1RL1-IL1RAP complex polymorphisms affect the development of asthma, airway inflammation, and subsequent ICS response in childhood.
Promoting a Syndemic Approach for Cardiometabolic Disease Management During COVID-19: The CAPISCO International Expert Panel
Authors: Al Mahmeed Wael , Al-Rasadi Khalid , Banerjee Yajnavalka , Ceriello Antonio , Cosentino Francesco , Galia Massimo , Goh Su-Yen , Kempler Peter , Lessan Nader , Papanas Nikolaos , Rizvi Ali A. , Santos Raul D. , Stoian Anca P. , Toth Peter P. , Rizzo Manfredi ,   The CArdiometabolic Panel of International experts on Syndemic COvid-19 (CAPISCO)
Published: December 2021

Efforts in the fight against COVID-19 are achieving success in many parts of the world, although progress remains slow in other regions. We believe that a syndemic approach needs to be adopted to address this pandemic given the strong apparent interplay between COVID-19, its related complications, and the socio-structural environment. We have assembled an international, multidisciplinary group of researchers and clinical practitioners to promote a novel syndemic approach to COVID-19: the CArdiometabolic Panel of International experts on Syndemic COvid-19 (CAPISCO). This geographically diverse group aims to facilitate collaborative-networking and scientific exchanges between researchers and clinicians facing a multitude of challenges on different continents during the pandemic. In the present article we present our “manifesto”, with the intent to provide evidence-based guidance to the global medical and scientific community for better management of patients both during and after the current pandemic.
Solutions to Big Data Privacy and Security Challenges Associated With COVID-19 Surveillance Systems
Authors: Bentotahewa Vibhushinie , Hewage Chaminda , Williams Jason
Published: December 2021

The growing dependency on digital technologies is becoming a way of life, and at the same time, the collection of data using them for surveillance operations has raised concerns. Notably, some countries use digital surveillance technologies for tracking and monitoring individuals and populations to prevent the transmission of the new coronavirus. The technology has the capacity to contribute towards tackling the pandemic effectively, but the success also comes at the expense of privacy rights. The crucial point to make is regardless of who uses and which mechanism, in one way another will infringe personal privacy. Therefore, when considering the use of technologies to combat the pandemic, the focus should also be on the impact of facial recognition cameras, police surveillance drones, and other digital surveillance devices on the privacy rights of those under surveillance. The GDPR was established to ensure that information could be shared without causing any infringement on personal data and businesses; therefore, in generating Big Data, it is important to ensure that the information is securely collected, processed, transmitted, stored, and accessed in accordance with established rules. This paper focuses on Big Data challenges associated with surveillance methods used within the COVID-19 parameters. The aim of this research is to propose practical solutions to Big Data challenges associated with COVID-19 pandemic surveillance approaches. To that end, the researcher will identify the surveillance measures being used by countries in different regions, the sensitivity of generated data, and the issues associated with the collection of large volumes of data and finally propose feasible solutions to protect the privacy rights of the people, during the post-COVID-19 era.
Zircon of Triassic Age in the Stuttgart Formation (Schilfsandstein)—Witness of Tephra Fallout in the Central European Basin and New Constraints on the Mid-Carnian Episode
Authors: Zeh Armin , Franz Matthias , Obst Karsten
Published: December 2021

The Carnian Stuttgart-Formation (Schilfsandstein) of the Central European Basin contains relics of Triassic volcanic detritus in form of euhedral zircon grains and authigenic analcime. Multiple LA-ICP-MS spot analyses of single zircon crystals from an outcrop near Heilbronn (SW Germany) yielded weighted average 206Pb/238U ages between 250 and 230 Ma, providing evidence for tephra fallout in the southern part of the Central European Basin related to Olenekian, Anisian–Ladinian and Carnian volcanic activity. The tephra was probably transported by monsoonal circulations from volcanic centres of the NW Tethys to the Central European Basin. The four youngest zircon crystals gave a weighted average 206Pb/238U age of 231.1 ± 1.6 Ma (10 analyses), which is interpreted to date syn-depositional tephra fallout into the fluvial Lower Schilfsandstein Member of the Stuttgart Formation. This new maximum depositional age provides the first evidence that deposition of the Stuttgart Formation, which represents the type-example of the mid-Carnian episode, a global episode of enhanced flux of siliciclastic detritus and related environmental perturbations, occurred during the Tuvalian 2 substage at ca. 231 Ma, about 3 million years later than suggested by previous correlations. Zircon grains with weighted average 206Pb/238U ages of 236.0 ± 1.2 Ma (n = 17) and 238.6 ± 1.5 Ma (n = 6) and 206Pb/238U ages between 241 ± 6 and 250 ± 3 Ma point to the presence of tephra in early Carnian to Olenekian strata of the Keuper to Buntsandstein Groups. Traces of these reworked tephra were incorporated into the Stuttgart Formation due to fluvial erosion in the southern Central European Basin and at its margins.
Early Versus Routine Oral Glucose Tolerance Test in Women With Intermediate Hyperglycemia at First Prenatal Visit: A Retrospective Cohort Study in China
Authors: Ye Yunzhen , Qin Kaizhou , Xiong Yu , Wu Jiangnan , Zhou Qiongjie , Xiao Xirong , Li Xiaotian
Published: December 2021

Background and Objectives

Intermediate hyperglycemia in the first half of pregnancy, defined as a fasting plasma glucose level between 5.1- 6.9 mM, increases the risk of gestational diabetes mellitus, but clinical evidence for further management is lacking. We aim to evaluate the effectiveness of an early oral glucose tolerance test (OGTT) followed by the identification of intermediate hyperglycemia on pregnancy outcomes in real world setting.

Subjects and Methods

A retrospective cohort study was conducted at the Obstetrics and Gynecology Hospital, Shanghai, China, between 2013 and 2017. Women with intermediate hyperglycemia at the first prenatal visit were identified and underwent an immediate (within one week) or a routine OGTT (24-28 gw) according to their wishes and received nutrition and exercise advice. Women diagnosed of gestational diabetes (GDM) were managed by standard interventions. Primary outcome was larger for gestational age (LGA). Secondary outcomes were primary cesarean delivery, preterm birth, shoulder dystocia or forceps delivery, preeclampsia, neonatal hypoglycemia, hyperbilirubinemia, and low Apgar score. Logistic regressions with or without a further propensity score-matched analysis were performed.

Results

Among 42406 women involved, 1104 (2.6%) with intermediate hyperglycemia at the first prenatal visit were identified, of whom 176 (15.9%) underwent an early OGTT and 741 (67.1%) received a routine OGTT. Logistic regression showed that an early OGTT was not significantly associated with an altered risk of LGA (adjusted OR 1.13, 95% CI 0.73-1.75) but was related to an increased odds for neonatal hyperbilirubinemia (adjusted OR 2.89; 95% CI 1.55-5.37). No significant associations were observed for other secondary outcomes. These trends remained consistent in propensity score-matched models.

Conclusions

Our data from a real-world setting did not support that an early OGTT among women with intermediate hyperglycemia at the first prenatal visit improved pregnancy outcomes.
The Uptake of Ethinyl-Estradiol and Cortisol From Water by Mussels (Mytilus spp.)
Authors: Katsiadaki Ioanna , Schwarz Tamar I. , Cousins Alex R. O. , Scott Alexander P.
Published: December 2021

Previous toxicokinetic studies have shown that mussels (Mytilus spp.) can readily absorb the three main mammalian sex steroids, estradiol (E2), testosterone (T) and progesterone (P) from water. They also have a strong ability to store E2 and the 5α-reduced metabolites of T and P in the form of fatty acid esters. These esters were shown to have half-lives that were measured in weeks (i.e. they were not subject to fast depuration). The present study looked at the toxicokinetic profile of two other common steroids that are found in water, the potent synthetic oestrogen, (ethinyl-estradiol) (EE2; one of the two components of ‘the pill’), and cortisol, a natural stress steroid in vertebrates. In the first three hours of uptake, tritiated EE2 was found to be taken up at a similar rate to tritiated E2. However, the levels in the water plateaued sooner than E2. The ability of the animals to both esterify and sulphate EE2 was found to be much lower than E2, but nevertheless did still take place. After 24 h of exposure, the majority of radiolabelled EE2 in the animals was present in the form of free steroid, contrary to E2, which was esterified. This metabolism was reflected in a much lower half-life (of only 15 h for EE2 in the mussels as opposed to 8 days for E2 and >10 days for T and P). Intriguingly, hardly any cortisol (in fact none at all in one of the experiments) was absorbed by the mussels. The implications of this finding in both toxicokinetic profiling and evolutionary significance (why cortisol might have evolved as a stress steroid in bony fishes) are discussed.
Fish Feed Intake, Feeding Behavior, and the Physiological Response of Apelin to Fasting and Refeeding
Authors: Assan Daniel , Huang Yanlin , Mustapha Umar Farouk , Addah Mercy Nabila , Li Guangli , Chen Huapu
Published: December 2021

Feed is one of the most important external signals in fish that stimulates its feeding behavior and growth. The intake of feed is the main factor determining efficiency and cost, maximizing production efficiency in a fish farming firm. The physiological mechanism regulating food intake lies between an intricate connection linking central and peripheral signals that are unified in the hypothalamus consequently responding to the release of appetite-regulating genes that eventually induce or hinder appetite, such as apelin; a recently discovered peptide produced by several tissues with diverse physiological actions mediated by its receptor, such as feed regulation. Extrinsic factors have a great influence on food intake and feeding behavior in fish. Under these factors, feeding in fish is decontrolled and the appetite indicators in the brain do not function appropriately thus, in controlling conditions which result in the fluctuations in the expression of these appetite-relating genes, which in turn decrease food consumption. Here, we examine the research advancements in fish feeding behavior regarding dietary selection and preference and identify some key external influences on feed intake and feeding behavior. Also, we present summaries of the results of research findings on apelin as an appetite-regulating hormone in fish. We also identified gaps in knowledge and directions for future research to fully ascertain the functional importance of apelin in fish.
Integrative Transcriptomics Reveals Activation of Innate Immune Responses and Inhibition of Inflammation During Oral Immunotherapy for Egg Allergy in Children
Authors: Karisola Piia , Palosuo Kati , Hinkkanen Victoria , Wisgrill Lukas , Savinko Terhi , Fyhrquist Nanna , Alenius Harri , Mäkelä Mika J.
Published: December 2021

We previously reported the results of a randomized, open-label trial of egg oral immunotherapy (OIT) in 50 children where 44% were desensitized and 46% were partially desensitized after 8 months of treatment. Here we focus on cell-mediated molecular mechanisms driving desensitization during egg OIT. We sought to determine whether changes in genome-wide gene expression in blood cells during egg OIT correlate with humoral responses and the clinical outcome. The blood cell transcriptome of 50 children receiving egg OIT was profiled using peripheral blood mononuclear cell (PBMC) samples obtained at baseline and after 3 and 8 months of OIT. We identified 467 differentially expressed genes (DEGs) after 3 or 8 months of egg OIT. At 8 months, 86% of the DEGs were downregulated and played a role in the signaling of TREM1, IL-6, and IL-17. In correlation analyses, Gal d 1–4-specific IgG4 antibodies associated positively with DEGs playing a role in pathogen recognition and antigen presentation and negatively with DEGs playing a role in the signaling of IL-10, IL-6, and IL-17. Desensitized and partially desensitized patients had differences in their antibody responses, and although most of the transcriptomic changes were shared, both groups had also specific patterns, which suggest slower changes in partially desensitized and activation of NK cells in the desensitized group. OIT for egg allergy in children inhibits inflammation and activates innate immune responses regardless of the clinical outcome at 8 months. Changes in gene expression patterns first appear as posttranslational protein modifications, followed by more sustained epigenetic gene regulatory functions related to successful desensitization.
Tocilizumab (TCZ) Decreases Angiogenesis in Rheumatoid Arthritis Through Its Regulatory Effect on miR-146a-5p and EMMPRIN/CD147
Authors: Zisman Devy , Safieh Mirna , Simanovich Elina , Feld Joy , Kinarty Amalia , Zisman Liron , Gazitt Tal , Haddad Amir , Elias Muna , Rosner Itzhak , Kaly Lisa , Rahat Michal A.
Published: December 2021

Background

Angiogenesis is a major contributor to the development of inflammation during Rheumatoid arthritis (RA), as the vascularization of the pannus provides nutrients and oxygen for the infiltrating immune cells and proliferating synoviocytes. Tocilizumab (TCZ) is an anti-IL-6 receptor antibody that is used in the treatment of RA patients, and has been shown to exert anti-inflammatory effects. However, its effects on angiogenesis are not fully elucidated, and the molecular mechanisms regulating this effect are unknown.

Methods

We evaluated the concentrations of several pro- and anti-angiogenic factors and the expression levels of several microRNA molecules that are associated with RA and angiogenesis in serum samples obtained from 40 RA patients, before and 4 months after the initiation of TCZ treatment. Additionally, we used an in vitro co-culture system of fibroblasts (the HT1080 cell line) and monocytes (the U937 cell line) to explore the mechanisms of TCZ action.

Results

Serum samples from RA patients treated with TCZ exhibited reduced circulating levels of EMMPRIN/CD147, enhanced expression of circulating miR-146a-5p and miR-150-5p, and reduced the angiogenic potential as was manifested by the lower number of tube-like structures that were formed by EaHy926 endothelial cell line. In vitro, the accumulation in the supernatants of the pro-angiogenic factors EMMPRIN, VEGF and MMP-9 was increased by co-culturing the HT1080 fibroblasts and the U937 monocytes, while the accumulation of the anti-angiogenic factor thrombospondin-1 (Tsp-1) and the expression levels of miR-146a-5p were reduced. Transfection of HT1080 cells with the miR-146a-5p mimic, decreased the accumulation of EMMPRIN, VEGF and MMP-9. When we neutralized EMMPRIN with a blocking antibody, the supernatants derived from these co-cultures displayed reduced migration, proliferation and tube formation in the functional assays.

Conclusions

Our findings implicate miR-146a-5p in the regulation of EMMPRIN and propose that TCZ affects angiogenesis through its effects on EMMPRIN and miR-146a-5p.
Allogeneic Vγ9Vδ2 T-Cell Therapy Promotes Pulmonary Lesion Repair: An Open-Label, Single-Arm Pilot Study in Patients With Multidrug-Resistant Tuberculosis
Authors: Liang Juan , Fu Liang , Li Man , Chen Yuyuan , Wang Yi , Lin Yi , Zhang Hailin , Xu Yan , Qin Linxiu , Liu Juncai , Wang Weiyu , Hao Jianlei , Liu Shuyan , Zhang Peize , Lin Li , Alnaggar Mohammed , Zhou Jie , Zhou Lin , Guo Huixin , Wang Zhaoqin , Liu Lei , Deng Guofang , Zhang Guoliang , Wu Yangzhe , Yin Zhinan
Published: December 2021

The WHO’s “Global tuberculosis report 2020” lists tuberculosis (TB) as one of the leading causes of death globally. Existing anti-TB therapy strategies are far from adequate to meet the End TB Strategy goals set for 2035. Therefore, novel anti-TB therapy protocols are urgently needed. Here, we proposed an allogeneic Vγ9Vδ2 T-cell-based immunotherapy strategy and clinically evaluated its safety and efficacy in patients with multidrug-resistant TB (MDR-TB). Eight patients with MDR-TB were recruited in this open-label, single-arm pilot clinical study. Seven of these patients received allogeneic Vγ9Vδ2 T-cell therapy adjunct with anti-TB drugs in all therapy courses. Cells (1 × 108) were infused per treatment every 2 weeks, with 12 courses of cell therapy conducted for each patient, who were then followed up for 6 months to evaluate the safety and efficacy of cell therapy. The eighth patient initially received four courses of cell infusions, followed by eight courses of cell therapy plus anti-MDR-TB drugs. Clinical examinations, including clinical response, routine blood tests and biochemical indicators, chest CT imaging, immune cell surface markers, body weight, and sputum Mycobacterium tuberculosis testing, were conducted. Our study revealed that allogeneic Vγ9Vδ2 T cells are clinically safe for TB therapy. These cells exhibited clinical efficacy in multiple aspects, including promoting the repair of pulmonary lesions, partially improving host immunity, and alleviating M. tuberculosis load in vivo, regardless of their application in the presence or absence of anti-TB drugs. This pilot study opens a new avenue for anti-TB treatment and exhibits allogeneic Vγ9Vδ2 T cells as promising candidates for developing a novel cell drug for TB immunotherapy.

Clinical Trial Registration

(https://clinicaltrials.gov/ct2/results?cond=&term=NCT03575299&cntry=&state=&city=&dist=) ( NCT03575299).
Good Tumor Response to Chemoradioimmunotherapy in dMMR/MSI-H Advanced Colorectal Cancer: A Case Series
Authors: Zhou Chengjing , Jiang Ting , Xiao Yajie , Wang Qiaoxuan , Zeng Zhifan , Cai Peiqiang , Zhao Yongtian , Zhao Zhikun , Wu Dongfang , Lin Hanqing , Sun Chao , Zhang Rong , Xiao Weiwei , Gao Yuanhong
Published: December 2021

Purpose

Immune checkpoint blockade has led to a significant improvement of patient survival in metastatic colorectal cancer (CRC) with DNA mismatch repair-deficiency (dMMR)/microsatellite instability-high (MSI-H). However, not all these patients are sensitive to monoimmunotherapy. We firstly presented a case series of advanced dMMR/MSI-H CRCs treating with PD-1 inhibitor-based chemoradioimmunotherapy (CRIT).

Methods and Materials

We assessed the short-term efficacy and safety of CRIT in advanced dMMR/MSI-H CRCs, and also did next-generation sequencing (NGS) assays.

Results

Our analysis included five advanced dMMR/MSI-H CRCs who have received toripalimab-based CRIT. Toripalimab was given 240mg every three weeks, and the radiation dose was 45-50 gray in 25 fractions. Chemotherapy regimens consisted of CAPOX in three patients, capecitabine in one patient, and mFOLFOX6 in one patient. Initially, two patients displayed complete response (CR), and three patients achieved partial response (PR) on imaging findings. Afterwards, one PR patient was confirmed pathological complete response after surgery, leading to three CR cases in total. Hematological toxicity was the most common adverse effect, and only two patients developed mild immune-related adverse effects besides. All the treatment-related adverse events were under control. Based on the NGS results, the median intratumor heterogeneity was 0.19 (range 0-0.957), which was less in CR patients than PR patients (P = 0.019). Genetic mutations at DNA damage repair genes and the JAK1 gene were also observed.

Conclusions

For advanced dMMR/MSI-H CRC, anti-PD-1 based CRIT is effective and safe. Further studies are required to better clarify the potential role and mechanism of CRIT as a viable therapeutic strategy in this population.
Novel Use of Low-Dose Radiotherapy to Modulate the Tumor Microenvironment of Liver Metastases
Authors: He Kewen , Barsoumian Hampartsoum B. , Bertolet Genevieve , Verma Vivek , Leuschner Carola , Koay Eugene J. , Ludmir Ethan B. , Hsu Ethan , Pisipati Esha , Voss Tiffany A. , Puebla-Osorio Nahum , Cortez Maria Angelica , Welsh James W.
Published: December 2021

Despite multiple therapeutic approaches, the presence of liver metastases carries a guarded prognosis, urgently necessitating further clinical and scientific research to develop curative interventions. The liver is an immunoprivileged organ that suppresses the effectiveness of immunotherapies in patients with hepatic metastases. Cancer immunotherapies have been successfully bolstered by low-dose radiotherapy (LDRT), which is capable of reprogramming the tumor microenvironment (TME) from an immunosuppressive to an immunostimulatory one. Likewise, LDRT may be able to revoke the immune privilege enjoyed by the liver, permitting successful immunotherapies there. Here, we first review challenges that face the treatment of liver metastases. We next outline emerging preclinical and clinical evidence supporting enhanced systemic tumor control of LDRT in the context of cancer immunotherapy. Finally, we will discuss the rationale of combining liver-directed LDRT with immunostimulatory strategies to overcome immune resistance and achieve better clinical response. This notion is supported by a recent case study in which a patient who had progressed following T cell therapy experienced a complete response after LDRT to the liver.
Climate Change Induced Coastline Change Adjacent to Small Tidal Inlets
Authors: Duong Trang Minh
Published: December 2021

The many thousands of small tidal inlets (STIs), and their adjacent coastlines, are almost certain to be affected by climate change in multiple ways, due to their behaviour being closely linked to both oceanic and terrestrial drivers such as riverflow, sea level, and ocean waves, all which are projected to change over the 21st century. Development of risk informed adaptation strategies for these highly utilized and inhabited inlet-interrupted coast zones requires projections of both alongshore average coastline recession and alongshore variability in coastline position along the coast under future forcing conditions, the latter being an aspect that has not received much attention to date. Here, a combination of a process-based morphodynamic model (Delft3D) and the reduced complexity coastline model (SMIC), concurrently forced with tides, waves, riverflows, and sea level rise, is used to investigate both of these phenomena at STI-interrupted coasts. The models are here applied to schematised conditions representing two systems in Sri Lanka, representing two of the three main Types of STIs: Negombo lagoon – permanently open, locationally stable inlet (Type 1), and Kalutara lagoon – permanently open, alongshore migrating inlet (Type 2). Results indicate that, under a high emissions climate scenario following RCP 8.5, by end-century, the coastline adjacent to the Type 1 STI may experience an alongshore average recession as large as 200 m, and that the alongshore variability in coastline position may be up to twice that at present. The Type 2 STI is projected to experience an alongshore average coastline recession of about 120 m, and up to a 75% increase in alongshore variability in coastline position by end-century, relative to the present. Thus, both the alongshore average coastline recession and the increase in the alongshore variability in coastline position are greater at the Type 1 STI, compared to at the Type 2 STI. These findings highlight the importance of accounting for both alongshore average coastline recession and future changes in alongshore variability in coastline position when assessing coastal hazards and risk on inlet-interrupted coasts to adequately inform climate adaptation strategies.
Roles of Crustacean Female Sex Hormone 1a in a Protandric Simultaneous Hermaphrodite Shrimp
Authors: Liu Fang , Shi Wenyuan , Huang Lin , Wang Guizhong , Zhu Zhihuang , Ye Haihui
Published: December 2021

Crustacean female sex hormone (CFSH) plays a pivotal role in the development of secondary sex characteristics in dioecious crustaceans. However, until now the knowledge concerning its functions in hermaphroditic species is scanty. Herein, we explored the function of CFSH (Lvit-CFSH1a) in the peppermint shrimp Lysmata vittata, a species characterized by a rare reproductive system of protandric simultaneous hermaphroditism (PSH). Lvit-CFSH1a cDNA was 1,220-bp in length with a 720-bp ORF encoded a polypeptide of 239-aa. RT-PCR showed that Lvit-CFSH1a was exclusively expressed in the eyestalk ganglion. For female physiology, it was found that Lvit-CFSH1a was indispensable for the development of female gonopores, but it might not involve vitellogenesis of the species. For male physiology, Lvit-CFSH1a suppressed Lvit-IAG2 expression in short-term silencing experiment and recombinant protein injection experiment, but did not affect male sexual differentiation in long-term silencing experiment. In addition, silencing the Lvit-CFSH1a gene impeded individual growth in L. vittata.
Based on Network Pharmacology Tools to Investigate the Mechanism of Tripterygium wilfordii Against IgA Nephropathy
Authors: Xia Ming , Liu Di , Liu Haiyang , Zhao Juanyong , Tang Chengyuan , Chen Guochun , Liu Yu , Liu Hong
Published: December 2021

Background: Immunoglobulin A nephropathy (IgAN) is the most common primary glomerular disease and poses a global major public health burden. The preparation of Tripterygium wilfordii Hook F (TwHF) is widely applied for treating patients with Immunoglobulin A nephropathy in China, while the molecular mechanisms remain unclear. This study aimed to verify the therapeutic mechanism of TwHF on IgAN by undertaking a holistic network pharmacology strategy in combination with in vitro and in vivo experiments.

Methods: TwHF active ingredients and their targets were obtained via the Traditional Chinese Medicine Systems Pharmacology Database. The collection of IgAN-related target genes was collected from GeneCards and OMIM. TwHF-IgAN common targets were integrated and visualized by Cytoscape. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to determine the predominant molecular mechanisms and pathways of TwHF on the treatment of IgAN. The protein-protein interaction network was constructed by the STRING online search tool, and hub genes were identified using R software. The expression of hub gene and related signaling were evaluated in TwHF-treated mice through immunohistochemistry and western blot and further validated in human mesangial cells (HMCs). In addition, Cell counting kit 8 (CCK8) and flow cytometry were used to detect the effects of TwHF on cell proliferation and cell cycle of mesangial cells.

Results: A total of 51 active ingredients were screened from TwHF and 61 overlapping targets related to IgAN were considered potential therapeutic targets, GO functions and KEGG analyses demonstrated that these genes were primarily associated with DNA-binding transcription factor binding, lipid and atherosclerosis pathway. Genes with higher degrees including AKT1, CXCL8, MMP9, PTGS2, CASP3, JUN are hub genes of TwHF against IgAN. Verification of hub gene JUN both in vitro and in vivo showed that TwHF significantly attenuated JUN phosphorylation in the kidneys of IgAN mice and aIgA1-activated HMCs, meanwhile suppressing HMCs proliferation and arresting G1-S cell cycle progression.

Conclusion: Our research strengthened the mechanisms of TwHF in treating IgAN, inhibition of JUN activation may play a pivotal role in TwHF in alleviating IgAN renal injury.
Apple Pomace as a Sustainable Substrate in Sourdough Fermentation
Authors: Martău Gheorghe Adrian , Teleky Bernadette-Emőke , Ranga Floricuţa , Pop Ioana Delia , Vodnar Dan Cristian
Published: December 2021

Innovations range from food production, land use, and emissions all the way to improved diets and waste management. Global apple production has amounted to over 87 million tons/year, while 18% are processed, resulting in 20–35% (apple fruit fresh weight) apple pomace (AP). Using modern AP management, integrated knowledge in innovative fermentation demonstrates opportunities for reducing environmental pollution and integration into a circular economy. With this association in view, integrating AP flour during sourdough fermentation increases the nutritional value, highlighting a new approach that could guide innovative fermented foods. In this study, the wheat flour (WF) and AP flour were mixed at different ratios, hydrated with water (1:1 w/v), and fermented using a selective culture of Fructilactobacillus florum DSM 22689 and baker’s yeast (single and co-culture). Sourdough fermentation was monitored and analyzed for 72 h. Results suggested that AP may be an important source of organic acids and fermentable sugars that increase nutritional sourdough value. AP flour addition in WF had a positive effect, especially in fermentations with 95% WF and 5% AP, mainly in co-culture fermentation.
Root-Derived Endophytic Diazotrophic Bacteria Pantoea cypripedii AF1 and Kosakonia arachidis EF1 Promote Nitrogen Assimilation and Growth in Sugarcane
Authors: Singh Rajesh Kumar , Singh Pratiksha , Guo Dao-Jun , Sharma Anjney , Li Dong-Ping , Li Xiang , Verma Krishan K. , Malviya Mukesh Kumar , Song Xiu-Peng , Lakshmanan Prakash , Yang Li-Tao , Li Yang-Rui
Published: December 2021

Excessive, long-term application of chemical fertilizers in sugarcane crops disrupts soil microbial flora and causes environmental pollution and yield decline. The role of endophytic bacteria in improving crop production is now well-documented. In this study, we have isolated and identified several endophytic bacterial strains from the root tissues of five sugarcane species. Among them, eleven Gram-negative isolates were selected and screened for plant growth-promoting characteristics, i.e., production of siderophores, indole-3-acetic acid (IAA), ammonia, hydrogen cyanide (HCN), and hydrolytic enzymes, phosphorus solubilization, antifungal activity against plant pathogens, nitrogen-fixation, 1-aminocyclopropane-1-carboxylic acid deaminase activity, and improving tolerance to different abiotic stresses. These isolates hadnifH(11 isolates),acdS(8 isolates), andHCN(11 isolates) genes involved in N-fixation, stress tolerance, and pathogen biocontrol, respectively. Two isolatesPantoea cypripediiAF1andKosakonia arachidisEF1 were the most potent strains and they colonized and grew in sugarcane plants. Both strains readily colonized the leading Chinese sugarcane variety GT42 and significantly increased the activity of nitrogen assimilation enzymes (glutamine synthetase, NADH glutamate dehydrogenase, and nitrate reductase), chitinase, and endo-glucanase and the content of phytohormones gibberellic acid, indole-3-acetic acid, and abscisic acid. The gene expression analysis of GT42 inoculated with isolates ofP. cypripediiAF1 orK. arachidisEF1 showed increased activity ofnifHand nitrogen assimilation genes. Also, the inoculated diazotrophs significantly increased plant nitrogen content, which was corroborated by the15N isotope dilution analysis. Collectively, these findings suggest thatP. cypripediiandK. arachidisare beneficial endophytes that could be used as a biofertilizer to improve plant nitrogen nutrition and growth of sugarcane. To the best of our knowledge, this is the first report of sugarcane growth enhancement and nitrogen fixation by Gram-negative sugarcane root-associated endophytic bacteriaP. cypripediiandK. arachidis. These strains have the potential to be utilized as sugarcane biofertilizers, thus reducing nitrogen fertilizer use and improving disease management.
Secretion Systems in Gram-Negative Bacterial Fish Pathogens
Authors: Mekasha Sophanit , Linke Dirk
Published: December 2021

Bacterial fish pathogens are one of the key challenges in the aquaculture industry, one of the fast-growing industries worldwide. These pathogens rely on arsenal of virulence factors such as toxins, adhesins, effectors and enzymes to promote colonization and infection. Translocation of virulence factors across the membrane to either the extracellular environment or directly into the host cells is performed by single or multiple dedicated secretion systems. These secretion systems are often key to the infection process. They can range from simple single-protein systems to complex injection needles made from dozens of subunits. Here, we review the different types of secretion systems in Gram-negative bacterial fish pathogens and describe their putative roles in pathogenicity. We find that the available information is fragmented and often descriptive, and hope that our overview will help researchers to more systematically learn from the similarities and differences between the virulence factors and secretion systems of the fish-pathogenic species described here.
Comparative Transcriptome Analysis of Genes Involved in Sesquiterpene Alkaloid Biosynthesis in Trichoderma longibrachiatum MD33 and UN32
Authors: Qian Xu , Jin Hui , Chen Zhuojun , Dai Qingqing , Sarsaiya Surendra , Qin Yitong , Jia Qi , Jin Leilei , Chen Jishuang
Published: December 2021

Trichoderma longibrachiatum MD33, a sesquiterpene alkaloid-producing endophyte isolated from Dendrobium nobile, shows potential medical and industrial applications. To understand the molecular mechanisms of sesquiterpene alkaloids production, a comparative transcriptome analysis was performed on strain MD33 and its positive mutant UN32, which was created using Ultraviolet (UV) mutagenesis and nitrogen ion (N+) implantation. The alkaloid production of UN32 was 2.62 times more than that of MD33. One thousand twenty-four differentially expressed genes (DEGs), including 519 up-regulated and 505 down-regulated genes, were identified. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed 139 GO terms and 87 biosynthesis pathways. Dendrobine, arguably the main sesquiterpene alkaloid the strain MD33 produced, might start synthesis through the mevalonate (MVA) pathway. Several MVA pathway enzyme-coding genes (hydroxy-methylglutaryl-CoA synthase, mevalonate kinase, and farnesyl diphosphate synthase) were found to be differentially expressed, suggesting that physical mutagenesis can disrupt genome integrity and gene expression. Some backbone post-modification enzymes and transcript factors were either discovered, suggesting the sesquiterpene alkaloid metabolism in T. longibrachiatum is a complex genetic network. Our findings help to shed light on the underlying molecular regulatory mechanism of sesquiterpene alkaloids production in T. longibrachiatum.
Contribution of Brain Processes to Tissue Loss After Spinal Cord Injury: Does a Pain-Induced Rise in Blood Pressure Fuel Hemorrhage?
Authors: Fauss Gizelle N. K. , Strain Misty M. , Huang Yung-Jen , Reynolds Joshua A. , Davis Jacob A. , Henwood Melissa K. , West Christopher R. , Grau James W.
Published: December 2021

Pain (nociceptive) input soon after spinal cord injury (SCI) expands the area of tissue loss (secondary injury) and impairs long-term recovery. Evidence suggests that nociceptive stimulation has this effect because it promotes acute hemorrhage. Disrupting communication with the brain blocks this effect. The current study examined whether rostral systems exacerbate tissue loss because pain input drives an increase in systolic blood pressure (BP) and flow that fuels blood infiltration. Rats received a moderate contusion injury to the lower thoracic (T12) spinal cord. Communication with rostral processes was disrupted by cutting the spinal cord 18 h later at T2. Noxious electrical stimulation (shock) applied to the tail (Experiment 1), or application of the irritant capsaicin to one hind paw (Experiment 2), increased hemorrhage at the site of injury. Shock, but not capsaicin, increased systolic BP and tail blood flow in sham-operated rats. Cutting communication with the brain blocked the shock-induced increase in systolic BP and tail blood flow. Experiment 3 examined the effect of artificially driving a rise in BP with norepinephrine (NE) in animals that received shock. Spinal transection attenuated hemorrhage in vehicle-treated rats. Treatment with NE drove a robust increase in BP and tail blood flow but did not increase the extent of hemorrhage. The results suggest pain input after SCI can engage rostral processes that fuel hemorrhage and drive sustained cardiovascular output. An increase in BP was not, however, necessary or sufficient to drive hemorrhage, implicating other brain-dependent processes.
Prognostic Factors and Clinical Characteristics of Duodenal Adenocarcinoma With Survival: A Retrospective Study
Authors: Sun Huapeng , Liu Yi , Lv Long , Li Jingwen , Liao Xiaofeng , Gong Wei
Published: December 2021

Background

To evaluate the clinical risk factors that influence the overall survival in patients with duodenal adenocarcinoma (DA) after tumor resection.

Methods

This study retrospectively analyzed 188 patients who underwent tumor resection for DA between January 2005 and June 2020 at Xiangyang Central Hospital.

Results

The median survival of the patients who underwent resectional operation was 54 months, longer than of those who underwent palliative surgery (20.8 months) (2,916.17; 95% CI, 916.3−9,280.5; p < 0.001). Survival of non-ampullary duodenal carcinoma patients (50.3 months; 95% CI, 39.7−61.8) was similar to that of ampullary duodenal carcinoma patients (59.3 months; 95% CI, 38.6−66.7) but was significantly better than that of papillary adenocarcinoma patients (38.9 months; 95% CI, 29.8−54.8; p = 0.386). Those with intestinal-type ductal adenocarcinomas had a longer median overall survival than those with the gastric type (61.8 vs. 46.7 months; p < 0.01) or pancreatic type (32.2 months; p < 0.001). Clinical DA samples had significantly diverse expressions of ATG12, IRS2, and IGF2. Higher expressions of the ATG12 and IRS2 proteins were significantly correlated with worse survival. Multivariate Cox regression analysis revealed that lymph node metastasis (hazard ratio (HR), 6.44; 95% CI, 3.68−11.27; p < 0.0001), margin status (HR, 4.94; 95% CI, 2.85−8.54; p < 0.0001), and high expression of ATG12 (HR, 1.89; 95% CI, 1.17−3.06; p = 0.0099) were independent prognostic factors negatively associated with survival in patients undergoing curative resection. There was no survival difference between the groups with ampullary, non-ampullary, and papillary adenocarcinomas treated with adjuvant chemotherapy (p = 0.973).

Conclusion

Gastric/pancreatic type, high expression of ATG12, lymph node metastases, and margin status were negative prognosticators of survival in patients with DAs than in those with tumor anatomical location. Curative resection is the best treatment option for appropriate patients.