bluuebunny/crossref_metadata_2025 huggingface dataset:
Dual effect of dietary seaweed of extract nanoparticles (GNS) with bionanocomposite cellulose acetate membranes (CA/bio-AgNps) on growth performance and health status of the Nile tilapia (Oreochromis niloticus): Specification on feed utilization, immune system, and antiparasitic action
Authors: Radwan Mahmoud , El-Sharkawy Mahmoud A. , Negm Mohammed A. , Mohammadein Amaal , Malki Jamila S. Al , Al-Thomali Asma W. , Mohamed Ahmed M. , Yassir Shahd , Bashar Mansour A.E.
Published: October 2022

Seaweed draws a lot of attention for its vital role in aquaculture as it contains beneficial biological compounds that undoubtedly might help in the development of this field. The current study sheds light on the potential efficiency of dietary supplements of Grateloupia acuminata and G. doryphore (Halymeniaceae) nanoparticles (GNS) at different levels with bionanocomposite cellulose acetate membranes (CA/bio-AgNps) on improved growth performance, digestive enzyme activity, immunity, antioxidative, resistance against infectious pathogens, and characterization of water quality treated with CA/bio-AgNps that is used in rearing Nile tilapia (Oreochromis niloticus). Four concentrations (0.1, 0.25, 0.5, and 1.0 ml/L) of GNS extract were tested as potential anti-bacterial and for the efficacy of being parasitic. Fish with an average weight (24.46 ± 0. 50 g) were apportioned into six experimental groups (T0, T1, T2, T3, T4, and T5) represented as 0.0%, 0.0%, 0.1%, 0.25%, 0.5%, and 1.0% GNS in diets with CA/bio-AgNps, respectively. Injection of fish with Aeromonas hydrophila was performed at the end of the trial. Chemical and bacteriological water indices significantly showed improvement after being treated with CA/bio-AgNps than the control group. Growth, carcass composition, digestive enzyme, and hematological and biochemical indices were significantly noticed positive (p< 0.05), especially T4 and T5, than the control group. In parallel, a significant improvement was noticed in serum lysozyme, total immunoglobulin, complement C3, antioxidative enzyme, and the relative expression of hepatic and inflammatory genes with an increased level of GNS (p< 0.05) are upregulated than the control group. Remarkably, GNS-supplemented diets and extracts provided positive efficacy against A. hydrophila with a decreased percentage of fish mortality, besides efficacy on antibacterial strains and Cichlidogyrus tilapiae, respectively. To sum up, the seaweed extract with CA/bio-AgNps resulted in better growth performance of fish, antipathogenic effect, and health status. Furthermore, CA/bio-AgNps were vital in improving water characteristics. They should be studied and applied more in the future.
Particle trajectory of nonlinear progressive flexural-gravity waves in Lagrangian coordinates
Authors: Hsu Hung-Chu , Li Meng-Syue
Published: October 2022

In this paper, we study the particle dynamics of nonlinear flexural-gravity waves propagating in a finite water depth, which is the interaction between ice sheets and water flows. The nonlinear deformation of a floating elastic sheet is modeled by the Cosserat shell theory. The theoretical analysis is performed by a uniform asymptotic perturbation expansion. A third-order explicit parametric solution of particle trajectories in Lagrangian coordinates is presented. Taking the time average of particle motion, the mass transport velocity and the Lagrangian surface setup are also derived. Numerical simulations are computed. The influences of flexural rigidity on the water particle orbits and the mass transport velocity of nonlinear flexural-gravity waves are first discussed.
A nested quantitative PCR assay for detection of the hard clam pathogen Mucochytrium quahogii (=QPX) in environmental samples
Authors: Geraci-Yee Sabrina , Allam Bassem , Collier Jackie L.
Published: October 2022

Progress in understanding and managing QPX disease outbreaks in hard clams (Mercenaria mercenaria) has been limited by lack of insight into basic aspects of the biology and ecology of the opportunistic pathogen Mucochytrium quahogii (formerly QPX or Quahog Parasite Unknown). One barrier is that while several methods have been able to detect M. quahogii in seawater and sediment, its abundance was typically too low for reliable quantification by those methods. Here we describe the development and validation of a sensitive, M. quahogii-specific, nested quantitative PCR (nqPCR) assay following the Minimum Information for Publication of Quantitative Real-Time PCR Experiments (MIQE) guidelines. The assay reaches the theoretical limit of detection (LOD) of a PCR assay at 3 copies per reaction with excellent efficiency, linearity, and minimal sample PCR inhibition. The functionality of the assay was evaluated by quantifying M. quahogii in sediment and seawater samples, which revealed that M. quahogii was broadly distributed throughout the marine environment, detected in 75% of samples, with mean estimated abundance of 0.21 cells per mg sediment, 0.55 cells per ml bottom seawater, and 0.02 cells per ml surface seawater. M. quahogii was most prevalent and most abundant in sediment and bottom seawater samples, suggesting that the flocculent layer at the sediment-water interface is an important environmental reservoir where M. quahogii may interact with hard clams. This assay will serve as a valuable tool to better understand QPX disease dynamics and offers a model to guide development of similar assays for other important marine microbes typically present at similarly low abundance.
Tertiary lymphoid structures accompanied by fibrillary matrix morphology impact anti-tumor immunity in basal cell carcinomas
Authors: Byers Candice , Gill Melissa , Kurtansky Nicholas R. , Alessi-Fox Christi , Harman Maggie , Cordova Miguel , Gonzalez Salvador , Guitera Pascale , Rotemberg Veronica , Marghoob Ashfaq , Chen Chih-Shan Jason , Dy Jennifer , Kose Kivanc , Rajadhyaksha Milind , Sahu Aditi
Published: October 2022

Tertiary lymphoid structures (TLS) are specialized lymphoid formations that serve as local repertoire of T- and B-cells at sites of chronic inflammation, autoimmunity, and cancer. While presence of TLS has been associated with improved response to immune checkpoint blockade therapies and overall outcomes in several cancers, its prognostic value in basal cell carcinoma (BCC) has not been investigated. Herein, we determined the prognostic impact of TLS by relating its prevalence and maturation with outcome measures of anti-tumor immunity, namely tumor infiltrating lymphocytes (TILs) and tumor killing. In 30 distinct BCCs, we show the presence of TLS was significantly enriched in tumors harboring a nodular component and more mature primary TLS was associated with TIL counts. Moreover, assessment of the fibrillary matrix surrounding tumors showed discrete morphologies significantly associated with higher TIL counts, critically accounting for heterogeneity in TIL count distribution within TLS maturation stages. Specifically, increased length of fibers and lacunarity of the matrix with concomitant reduction in density and alignment of fibers were present surrounding tumors displaying high TIL counts. Given the interest in inducing TLS formation as a therapeutic intervention as well as its documented prognostic value, elucidating potential impediments to the ability of TLS in driving anti-tumor immunity within the tumor microenvironment warrants further investigation. These results begin to address and highlight the need to integrate stromal features which may present a hindrance to TLS formation and/or effective function as a mediator of immunotherapy response.
Effect of lactic acid bacteria, yeast, and their mixture on the chemical composition, fermentation quality, and bacterial community of cellulase-treated Pennisetum sinese silage
Authors: Liao Chaosheng , Tang Xiaolong , Li Maoya , Lu Guangrou , Huang Xiaokang , Li Lin , Zhang Mingjie , Xie Yixiao , Chen Chao , Li Ping
Published: October 2022

The present study investigated the effects of Lentilactobacillus buchneri, Saccharomyces cerevisiae, and a mixture of the two on the cellulose degradation and microbial community of cellulase-treated Pennisetum sinese (CTPS) during biological pretreatment. The CTPS was stored without additives (CK) or with L. buchneri (L), yeast (Y, S. cerevisiae), and their mixture (LY) under anaerobic conditions for 60 days. All inoculants enhanced the anaerobic fermentation of CTPS. In relative to L, inoculations with Y and LY decreased the cellulose level of fermented-CTPS by 8.90 ~ 17.13%. Inoculation with L inhibited the growth of Weissella cibaria during anaerobic storage. However, inoculations with LY increased the relative abundance of the homofermentative bacterium Lactiplantibacillus plantarum by 6.04%. Therefore, inoculating S. cerevisiae reduced the adverse effects of L. buchneri-stimulated fermentation on cellulose degradation by altering the bacterial community during anaerobic storage of P. sinese. This work provides a new insight for the subsequent anaerobic digestion of P. sinese.
A novel PGPF Penicillium olsonii isolated from the rhizosphere of Aeluropus littoralis promotes plant growth, enhances salt stress tolerance, and reduces chemical fertilizers inputs in hydroponic system
Authors: Tarroum Mohamed , Romdhane Walid Ben , Al-Qurainy Fahad , Ali Ahmed Abdelrahim Mohamed , Al-Doss Abdullah , Fki Lotfi , Hassairi Afif
Published: October 2022

The hydroponic farming significantly enhances the yield and enables multiple cropping per year. These advantages can be improved by using plant growth-promoting fungi (PGPF) either under normal or stress conditions. In this study, the fungal strain (A3) isolated from the rhizosphere of the halophyte plant Aeluropus littoralis was identified as Penicillium olsonii based on sequence homology of its ITS region. The A3 fungus was shown to be halotolerant (up to 1 M NaCl) and its optimal growth was at 27°C, but inhibited at 40°C. In liquid culture medium, the A3 produced indole acetic acid (IAA) especially in the presence of L-tryptophan. Tobacco plants grown under hydroponic farming system were used to evaluate the promoting activity of the direct effect of A3 mycelium (DE) and the indirect effect (IDE) of its cell-free culture filtrate (A3CFF). The results showed that for the two conditions (DE or IDE) the tobacco seedlings exhibited significant increase in their height, leaf area, dry weight, and total chlorophyll content. Interestingly, the A3CFF (added to the MS liquid medium or to nutrient solution (NS), prepared from commercial fertilizers) induced significantly the growth parameters, the proline concentration, the catalase (CAT) and the superoxide dismutase (SOD) activities of tobacco plants. The A3CFF maintained its activity even after extended storage at 4°C for 1 year. Since the A3 is a halotolerant fungus, we tested its ability to alleviate salt stress effects. Indeed, when added at 1:50 dilution factor to NS in the presence of 250 mM NaCl, the A3CFF enhanced the plant salt tolerance by increasing the levels of total chlorophyll, proline, CAT, and SOD activities. In addition, the treated plants accumulated less Na+ in their roots but more K+ in their leaves. The A3CFF was also found to induce the expression of five salt stress related genes (NtSOS1, NtNHX1, NtHKT1, NtSOD, and NtCAT1). Finally, we proved that the A3CFF can reduce by half the chemical fertilizers inputs. Indeed, the tobacco plants grown in a hydroponic system using 0.5xNS supplemented with A3CFF (1:50) exhibited significantly higher growth than those grown in 0.5xNS or 1xNS. In an attempt to explain this mechanism, the expression profile of some growth related genes (nitrogen metabolism (NR1, NRT1), auxin (TRYP1, YUCCA6-like), and brassinosteroid (DET2, DWF4) biosynthesis) was performed. The results showed that all these genes were up-regulated following plant treatment with A3CFF. In summary the results revealed that the halotolerant fungus P. olsonii can stimulates tobacco plant growth, enhances its salt tolerance, and reduces by half the required chemical fertilizer inputs in a hydroponic farming system.
Case report: Malignant proliferating trichilemmal tumor of the thumb
Authors: Wang Guojie , Zhou Xuan , Luo Junqi , Hu Qiyi , Zhang Jie
Published: October 2022

Proliferating trichilemmal tumor is a very rare benign tumor that has the potential to transition into a malignant tumor. PTT most commonly affects the scalps of women above 60 years old and is frequently misdiagnosed due to its rarity. Herein, we present a case of a 68-year-old man with a malignant proliferating trichilemmal tumor on his right thumb. X-ray image showed a soft tissue mass on his thumb accompanied by bone destruction, while 18F-FDG PET revealed a hypermetabolic mass in the first index with axillary lymph node metastasis.
A case report of primary cardiac angiosarcoma with DNMT3A gene mutation
Authors: Tian Kun , Liu Yating , Zhu Haiying , Wang Tao , Chen Tianxing , Pei Xiaxia , Song Feixue
Published: October 2022

Cardiac angiosarcoma is a rare disease with a high mortality rate despite its low incidence. Surgery is currently the mainstay treatment strategy for patients with this condition. Herein, we describe a case of primary cardiac angiosarcoma, including symptoms, examination findings, treatment strategy and prognosis. In 2020, the patient was admitted to our hospital, and Next-Generation Sequencing (NGS) revealed a mutation in the DNMT3A gene. Generally, DNMT3A mutations are most commonly seen in atherosclerosis and myeloid leukemia. To our knowledge, this is the first reported case of primary cardiac angiosarcoma with DNMT3A gene mutation.
Advances in the molecular characterization of multiple myeloma and mechanism of therapeutic resistance
Authors: Mejia Saldarriaga Mateo , Darwiche Walaa , Jayabalan David , Monge Jorge , Rosenbaum Cara , Pearse Roger N. , Niesvizky Ruben , Bustoros Mark
Published: October 2022

Recent insight in the genomic landscape of newly diagnosed multiple myeloma (NDMM) and its precursor conditions, monoclonal gammopathy of uncertain significance (MGUS), and smoldering myeloma have allowed the identification of patients with precursor conditions with a high risk of progression. These cases with “progressor” MGUS/SMM have a higher average mutation burden, have higher rates of mutations in specific genes such as MAPK, DNA repair, MYC, DIS3, and are enriched for specific mutational signatures when compared to non-progressors and are comparable to those found in NDMM. The highly preserved clonal heterogeneity seen upon progression of SMM, combined with the importance of these early variables, suggests that the identification of progressors based on these findings could complement and enhance the currently available clinical models based on tumor burden. Mechanisms leading to relapse/refractory multiple myeloma (RRMM) are of clinical interest given worse overall survival in this population. An Increased mutational burden is seen in patients with RRMM when compared to NDMM, however, there is evidence of branching evolution with many of these mutations being present at the subclonal level. Likewise, alterations in proteins associated with proteosome inhibitor and immunomodulatory drugs activity could partially explain clinical resistance to these agents. Evidence of chromosomal events leading to copy number changes is seen, with the presence of TP53 deletion, mutation, or a combination of both being present in many cases. Additional chromosomal events such as 1q gain and amplification may also interact and lead to resistance.
A meta-analysis and trial sequential analysis of high intensity focused ultrasound ablation combined with transhepatic arterial chemotherapy and embolization for hepatoma
Authors: Zhang Liang , Xu Kuishuai , Zhang Xuehui , Li Linqian , Chong Jing , Yu Ning
Published: October 2022

Objective

The efficacy of High Intensity Focused Ultrasound Ablation(HIFU) combined with Transhepatic Arterial Chemotherapy And Embolization(TACE) versus TACE alone in the treatment of hepatoma was evaluated by meta-analysis and trial sequential analyses(TSA).

Methods

Pubmed, Cochrane, Embase, Web of Science, Scoups and CNKI, CQVIP, Wanfang Data(China National Knowledge Infrastructure) databases were searched from database construction to April 2022, and randomized controlled trials were included. Revman and Stata software were used for meta-analysis of tumor changes, survival rate, laboratory indicators and adverse reactions in the included studies, and TSA0.9 was used for sequential analysis. Grade Pro was also used to evaluate the included indicators.

Results

Twelve studies were included with a sample size of 1025 cases. Meta-analysis showed that the tumor response rate in the combined treatment group was 1.54 times higher than that in TACE alone (OR: 2.54; 95%CI:1.81-3.57) and the 6-month to 5-year survival rate was 1-4 times higher, with statistically significant differences (P<0.05). Subgroup analysis showed that country, pathological type and study type were the sources of heterogeneity. Egger results showed that there was no publication bias (95%CI: -1.333, 3.552; Ppublication=0.276), and the sensitivity analysis results were reliable. TSA results suggest that there may be false positive results, which need to be further confirmed by more studies. Grade evaluation results indicated that the quality of evidence for response rate and one-year survival was low.

Conclusion

HIFU combined with TACE has better efficacy in the treatment of hepatoma, which is worthy of promotion. However, there may be false positive results in this study, which needs to be further verified by more extensive and more tests.
Unweaving the mitotic spindle: A focus on Aurora kinase inhibitors in lung cancer
Authors: Stefani Alessio , Piro Geny , Schietroma Francesco , Strusi Alessandro , Vita Emanuele , Fiorani Simone , Barone Diletta , Monaca Federico , Sparagna Ileana , Valente Giustina , Ferrara Miriam Grazia , D’Argento Ettore , Di Salvatore Mariantonietta , Carbone Carmine , Tortora Giampaolo , Bria Emilio
Published: October 2022

Lung cancer is one of the most aggressive malignancies, classified into two major histological subtypes: non-small cell lung cancer (NSCLC), that accounts for about 85% of new diagnosis, and small cell lung cancer (SCLC), the other 15%. In the case of NSCLC, comprehensive genome sequencing has allowed the identification of an increasing number of actionable targets, which have become the cornerstone of treatment in the advanced setting. On the other hand, the concept of oncogene-addiction is lacking in SCLC, and the only innovation of the last 30 years has been the introduction of immune checkpoint inhibitors in extensive stage disease. Dysregulation of cell cycle is a fundamental step in carcinogenesis, and Aurora kinases (AURKs) are a family of serine/threonine kinases that play a crucial role in the correct advance through the steps of the cycle. Hyperexpression of Aurora kinases is a common protumorigenic pathway in many cancer types, including NSCLC and SCLC; in addition, different mechanisms of resistance to anticancer drugs rely on AURK expression. Hence, small molecule inhibitors of AURKs have been developed in recent years and tested in several malignancies, with different results. The aim of this review is to analyze the current evidences of AURK inhibition in lung cancer, starting from preclinical rationale to finish with clinical trials available up to now.
Affinity probes based on small-molecule inhibitors for tumor imaging
Authors: Yi Xinzeyu , Wang Zheng , Hu Xiang , Yu Aixi
Published: October 2022

Methods for molecular imaging of target areas, including optical imaging, radionuclide imaging, magnetic resonance imaging and other imaging technologies, are helpful for the early diagnosis and precise treatment of cancers. In addition to cancer management, small-molecule inhibitors are also used for developing cancer target probes since they act as the tight-binding ligands of overexpressed proteins in cancer cells. This review aims to summarize the structural designs of affinity probes based on small-molecule inhibitors from the aspects of the inhibitor, linker, dye and radionuclide, and discusses the influence of the modification of these structures on affinity and pharmacokinetics. We also present examples of inhibitor affinity probes in clinical applications, and these summaries will provide insights for future research and clinical translations.
The prognostic value of Epstein−Barr virus infection in Hodgkin lymphoma: A systematic review and meta-analysis
Authors: Hu Jianyu , Zhang Xue , Tao Huan , Jia Yongqian
Published: October 2022

Introduction

Epstein−Barr virus (EBV) contributes significantly to the development and occurrence of B-cell lymphomas. However, the association between EBV infection status and clinical outcomes in Hodgkin lymphoma (HL) patients has long been controversial. Therefore, we aimed to estimate the prognostic significance of EBV infection in HL survival.

Methods

We searched PubMed, Embase, Web of Science, and the Cochrane Library for relevant cohort studies from the date of their inception to February 20, 2022. Hazard ratios (HRs) and 95% confidence intervals (CIs) for overall survival (OS), Failure-free survival (FFS), Progression-free survival (PFS), Event-free survival (EFS) and disease-specific survival (DSS) were extracted from the studies or calculated. Subgroup analyses were conducted independently on the five survival outcomes to investigate the source of heterogeneity.

Results

A total of 42 qualified studies involving 9570 patients were identified in our meta-analysis. There was an association between EBV positivity and significantly poorer OS (HR=1.443, 95% CI: 1.250-1.666) and DSS (HR=2.312, 95% CI: 1.799-2.972). However, the presence of EBV in HL showed no effect on FFS, PFS or EFS. In subgroup analyses of OS, DSS and FFS stratified by age groups, EBV positivity was associated with poorer prognosis in elderly patients. Meanwhile, in children and adolescents with EBV-positive HL, we also observed a trend toward a better prognosis, though the results were not statistically significant.

Conclusions

EBV-positive status is associated with poor OS and DSS in HL patients. EBV infection should therefore be considered a valuable prognostic marker and risk-stratifying factor in HL, especially in older patients.

Systematic Review Registration

https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022328708.
Down-regulated expression of CDK5RAP3 and UFM1 suggests a poor prognosis in gastric cancer patients
Authors: Lin Mi , Lian Ning-Zi , Cao Long-Long , Huang Chang-Ming , Zheng Chao-Hui , Li Ping , Xie Jian-Wei , Wang Jia-Bin , Lu Jun , Chen Qi-Yue , Li Ya-Han , Peng Zhu-Huai , Zhang Xiao-Yu , Mei Yi-Xian , Lin Jian-Xian
Published: October 2022

Purpose

The relationship between the CDK5RAP3 and UFM1 expression and the prolonged outcomes of patients who underwent gastric cancer (GC) surgery was investigated.

Methods

Single-sample gene set enrichment analysis (ssGSEA), unsupervised clustering and other methods were used to verify the relationship between CDK5RAP3 and UFM1 in GC through public databases. Additionally, CDK5RAP3 and UFM1 expression in cancerous and paracancerous tissues of GC was analysed in the context of patient prognosis.

Results

CDK5RAP3 and UFM1 expression was downregulated synchronously, the interaction was observed between the two proteins, and UFM1 and CDK5RAP3 expression was found to be inversely associated to AKT pathway activation. Prognostic analysis showed that the prognosis is poorer for low CDK5RAP3 and UFM1 patients, than for high CDK5RAP3 and/or UFM1 (p<0.001) patients, and this expression pattern was an independent predictor for overall survival of GC. Coexpression of CDK5RAP3 and UFM1 combined with TNM staging can improve the accuracy of prognosis prediction for patients (p <0.001).

Conclusions

It is confirmed in our findings that a combination of CDK5RAP3 and UFM1 can produce a more precise prediction model for GC patients’ survival.
Postoperative prolonged mechanical ventilation correlates to poor survival in patients with surgically treated spinal metastasis
Authors: Hamed Motaz , Brandecker Simon , Rana Shaleen , Potthoff Anna-Laura , Eichhorn Lars , Bode Christian , Schmeel Frederic Carsten , Radbruch Alexander , Schäfer Niklas , Herrlinger Ulrich , Köksal Mümtaz , Giordano Frank Anton , Vatter Hartmut , Schneider Matthias , Banat Mohammed
Published: October 2022

Objective

Patients with spinal metastasis (SM) are at advanced stages of systemic cancer disease. Surgical therapy for SM is a common treatment modality enabling histopathological diagnosis and the prevention of severe neurological deficits. However, surgery for SM in this vulnerable patient cohort may require prolonged postoperative intensive care treatment, which could adversely affect the anticipated benefit of the surgery. We therefore assessed postoperative prolonged mechanical ventilation (PMV) as an indicator for intensive care treatment with regard to potential correlations with early postoperative mortality and overall survival (OS).

Methods

Between 2015 and 2019, 198 patients were surgically treated for SM at the author´s neurosurgical department. PMV was defined as postoperative mechanical ventilation of more than 24 hours. A multivariate analysis was performed to identify pre- and perioperative collectable predictors for 30 days mortality.

Results

Twenty out of 198 patients (10%) with SM suffered from postoperative PMV. Patients with PMV exhibited a median OS rate of 1 month compared to 12 months for patients without PMV (p < 0.0001). The 30 days mortality was 70% and after one year 100%. The multivariate analysis identified “PMV > 24 hrs” (p < 0.001, OR 0.3, 95% CI 0.02-0.4) as the only significant and independent predictor for 30 days mortality (Nagelkerke’s R2 0.38).

Conclusions

Our data indicate postoperative PMV to significantly correlate to high early postoperative mortality rates as well as to poor OS in patients with surgically treated SM. These findings might encourage the initiation of further multicenter studies to comprehensively investigate PMV as a so far underestimated negative prognostic factor in the course of surgical treatment for SM.
Ultrasound super-resolution imaging for the differential diagnosis of thyroid nodules: A pilot study
Authors: Zhang Ge , Yu Jing , Lei Yu-Meng , Hu Jun-Rui , Hu Hai-Man , Harput Sevan , Guo Zhen-Zhong , Cui Xin-Wu , Ye Hua-Rong
Published: October 2022

Objective

Ultrasound imaging provides a fast and safe examination of thyroid nodules. Recently, the introduction of super-resolution imaging technique shows the capability of breaking the Ultrasound diffraction limit in imaging the micro-vessels. The aim of this study was to evaluate its feasibility and value for the differentiation of thyroid nodules.

Methods

In this study, B-mode, contrast-enhanced ultrasound, and color Doppler flow imaging examinations were performed on thyroid nodules in 24 patients. Super-resolution imaging was performed to visualize the microvasculature with finer details. Microvascular flow rate (MFR) and micro-vessel density (MVD) within thyroid nodules were computed. The MFR and MVD were used to differentiate the benign and malignant thyroid nodules with pathological results as a gold standard.

Results

Super-resolution imaging (SRI) technique can be successfully applied on human thyroid nodules to visualize the microvasculature with finer details and obtain the useful clinical information MVD and MFR to help differential diagnosis. The results suggested that the mean value of the MFR within benign thyroid nodule was 16.76 ± 6.82 mm/s whereas that within malignant thyroid was 9.86 ± 4.54 mm/s. The mean value of the MVD within benign thyroid was 0.78 while the value for malignant thyroid region was 0.59. MFR and MVD within the benign thyroid nodules were significantly higher than those within the malignant thyroid nodules respectively (p < 0.01).

Conclusions

This study demonstrates the feasibility of ultrasound super-resolution imaging to show micro-vessels of human thyroid nodules via a clinical ultrasound platform. The important imaging markers, such as MVD and MFR, can be derived from SRI to provide more useful clinical information. It has the potential to be a new tool for aiding differential diagnosis of thyroid nodules.
HPV vaccination in Latin America: Coverage status, implementation challenges and strategies to overcome it
Authors: Nogueira-Rodrigues Angélica , Flores Matheus Gonçalves , Macedo Neto Avelar Oliveira , Braga Lucélia Antunes Coutinho , Vieira Carolina Martins , Sousa-Lima Renata Maria de , de Andrade Diocésio Alves Pinto , Machado Karime Kalil , Guimarães Andrea Paiva Gadelha
Published: October 2022

Cervical cancer remains a leading cause of morbidity and mortality amongst females in Latin America (LATAM). Cervical cancer is a preventable disease and HPV vaccination is a main key strategy towards its elimination. This study analyzes HPV vaccine implementation current status and the main barriers to achieve adequate coverage in the region. Data from the nineteen sovereign states of LATAM (comprised of all Portuguese and Spanish-speaking nations located south of the United States) were collected, including year of HPV vaccine implementation, gender and age targets, the number of doses included in the public program and coverage by dose. Sixteen out of the 19 evaluated countries have already implemented HPV vaccination programs. However, despite its proven efficacy and safety, HPV vaccine uptake in LATAM has been lower than expected. There is an evident decline in adhesion, mainly regarding the second dose. Several reasons are probably involved, of note: limited knowledge of HPV and HPV vaccine, misguided safety concerns, high cost, cultural barriers, and the Covid19 pandemic. Proper strategies to overcome these barriers are needed to ensure successful uptake. Effective policies are: adopting the one dose schedule, delivering the vaccine on both health center and schools, and advising health professionals to recommend the vaccine. Further research regarding HPV vaccine hesitancy in Latin America is needed.
Surgical options of the breast and clinical outcomes of breast cancer patients after neoadjuvant chemotherapy: A single-center retrospective study
Authors: Sang Yuting , Zhou Xujie , Chi Weiru , Chen Jiajian , Yang Benlong , Hao Shuang , Huang Xiaoyan , Liu Guangyu , Shao Zhimin , Wu Jiong
Published: October 2022

Background

Neoadjuvant chemotherapy (NAC) has evolved significantly and has been widely accepted for downstaging disease in early-stage and locally advanced breast cancer patients. Since the optimal surgical intervention for patients receiving NAC remains controversial, we aim to investigate the survival outcome of patients treated with different surgical management.

Methods

A retrospective, nested case-control study was conducted in patients with invasive breast cancer that underwent NAC at Fudan University Shanghai Cancer Center from January 2010 to June 2019. Based on surgical intervention, patients were divided into mastectomy and breast conservation groups. Patients were matched on age at diagnosis, menopausal status, the year of the surgery, post neoadjuvant therapy pathological tumor (ypT) stage, post neoadjuvant therapy pathological node (ypN) stage, molecular subtypes, and axillary surgery by propensity score matching.

Results

A total of 2080 patients were enrolled in this study. Among them, 1819 (87.5%) patients were categorized as mastectomy group, and 261 (12.5%) patients were classed as breast conservation group. Over 9-years of research, the proportion of breast conservation steadily increased in patients after NAC. Data showed that younger (P<0.001) and pre-menopausal (P<0.001) patients with normal BMI (P=0.022) were more likely to receive breast conservation. Patients at advanced ypT stage (P<0.001), ypN stage (P<0.001), and clinical TNM stage (P<0.001) were more often to undergo mastectomy, while breast conservation rate was significantly higher in patients with triple-negative tumors (P=0.023). Compared with the mastectomy group, significant benefits in overall survival were observed in patients who received breast conservation (Hazard ratio 0.41, [95% confidence interval: 0.18-0.97]; p=0.049) in the matched cohort. There was no statistical difference between groups related to disease-free survival and locoregional recurrence.

Conclusions

Tumor biology can significantly impact the surgical decision in patients administrated with NAC. Breast conservation was a safe alternative for mastectomy in the NAC setting without compromising survival outcomes and locoregional control.
L1CAM expression in either metastatic brain lesion or peripheral blood is correlated with peripheral platelet count in patients with brain metastases from lung cancer
Authors: Wang Jia-Wei , Wang Hong-Liang , Liu Qi , Hu Ke , Yuan Qing , Huang Sheng-Kai , Wan Jing-Hai
Published: October 2022

Background

Systemic immune-inflammation states across the heterogeneous population of brain metastases from lung cancer are very important, especially in the context of complex brain-immune bidirectional communication. Previous studies from our team and others have shown that the L1 cell adhesion molecule (L1CAM) is deeply involved in the aggressive phenotype, immunosuppressive tumor microenvironment (TME), and metastasis during multiple malignancies, which may lead to an unfavorable outcome. However, little is known about the relationship between the L1CAM expression and the systemic immune-inflammation macroenvironment beyond the TME in brain metastases from lung cancer.

Methods

Two cohorts of patients with brain metastases from lung cancer admitted to the National Cancer Center, Cancer Hospital of Chinese Academy of Medical Sciences, were studied in the present research. The L1CAM expression in cranial metastatic lesions by immunohistochemistry was explored in patients treated with neurosurgical resection, whereas the L1CAM expression in peripheral blood by ELISA was tested in patients treated with non-surgical antitumor management. Furthermore, based on peripheral blood cell counts in the CBC test, six systemic immune-inflammation biomarkers [neutrophil count, lymphocyte count, platelet count, systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio] were calculated. Then, the relationship between the L1CAM expression and these systemic immune-inflammation biomarkers was analyzed. In addition, these systemic immune-inflammation biomarkers were also used to compare the systemic immune-inflammation states in two cohorts of patients with brain metastases from lung cancer.

Results

Positive L1CAM expressions in the metastatic brain lesions were accompanied with significantly increased peripheral platelet counts in patients treated with neurosurgical tumor resection (P < 0.05). Similarly, in patients treated with non-surgical antitumor management, L1CAM expressions in the peripheral blood were positively correlated with peripheral platelet counts (P < 0.05). In addition, patients prepared for neurosurgical tumor resection were presented with poorer systemic immune-inflammation states in comparison with the one with non-surgical antitumor management, which was characterized by a significant increase in peripheral neutrophil counts (P < 0.01), SII (P < 0.05), and NLR (P < 0.05) levels.

Conclusion

The L1CAM expression in either the metastatic brain lesion or peripheral blood is positively correlated with the peripheral platelet count in patients with brain metastases from lung cancer. In addition, brain metastases that are prepared for neurosurgical tumor resection show poor systemic immune-inflammation states.
Case report: Immunovirotherapy as a novel add-on treatment in a patient with thoracic NUT carcinoma
Authors: Kloker Linus D. , Calukovic Branko , Benzler Katrin , Golf Alexander , Böhm Sebastian , Günther Sven , Horger Marius , Haas Simone , Berchtold Susanne , Beil Julia , Carter Mary E. , Ganzenmueller Tina , Singer Stephan , Agaimy Abbas , Stöhr Robert , Hartmann Arndt , Duell Thomas , Mairhofer Sandra , Fohrer Fabian , Reinmuth Niels , Zender Lars , Lauer Ulrich M.
Published: October 2022

NUT carcinoma (NC) is a rare and extremely aggressive form of cancer, usually presenting with intrathoracic or neck manifestations in adolescents and young adults. With no established standard therapy regimen and a median overall survival of only 6.5 months, there is a huge need for innovative treatment options. As NC is genetically driven by a single aberrant fusion oncoprotein, it is generally characterized by a low tumor mutational burden, thus making it immunologically cold and insusceptible to conventional immunotherapy. Recently, we have demonstrated that oncolytic viruses (OVs) are able to specifically infect and lyse NC cells, thereby turning an immunologically cold tumor microenvironment into a hot one. Here, we report an intensive multimodal treatment approach employing for the first time an OV (talimogene laherparepvec (T-VEC); IMLYGIC®) together with the immune checkpoint inhibitor pembrolizumab as an add-on to a basic NC therapy (cytostatic chemotherapy, radiation therapy, epigenetic therapy) in a patient suffering from a large thoracic NC tumor which exhibits an aberrant, unique BRD3:NUTM1 fusion. This case demonstrates for the first time the feasibility of this innovative add-on immunovirotherapy regimen with a profound, repetitive and durable replication of T-VEC that is instrumental in achieving tumor stabilization and improvement in the patient´s quality of life. Further, a previously unknown BRD3:NUTM1 fusion gene was discovered that lacks the extraterminal domain of BRD3.
Crosstalk between TBK1/IKKε and the type I interferon pathway contributes to tubulointerstitial inflammation and kidney tubular injury
Authors: Córdoba-David Gina , García-Giménez Jorge , Cardoso Castelo-Branco Regiane , Carrasco Susana , Cannata Pablo , Ortiz Alberto , Ramos Adrián M.
Published: October 2022

The type I interferon (TI-IFN) pathway regulates innate immunity, inflammation, and apoptosis during infection. However, the contribution of the TI-IFN pathway or upstream signaling pathways to tubular injury in kidney disease is poorly understood. Upon observing evidence of activation of upstream regulators of the TI-IFN pathway in a transcriptomics analysis of murine kidney tubulointerstitial injury, we have now addressed the impact of the TI-IFN and upstream signaling pathways on kidney tubulointerstitial injury. In cultured tubular cells and kidney tissue, IFNα/β binding to IFNAR activated the TI-IFN pathway and recruited antiviral interferon-stimulated genes (ISG) and NF-κB-associated proinflammatory responses. TWEAK and lipopolysaccharide (LPS) signaled through TBK1/IKKε and IRF3 to activate both ISGs and NF-κB. In addition, TWEAK recruited TLR4 to stimulate TBK1/IKKε-dependent ISG and inflammatory responses. Dual pharmacological inhibition of TBK1/IKKε with amlexanox decreased TWEAK- or LPS-induced ISG and cytokine responses, as well as cell death induced by a complex inflammatory milieu that included TWEAK. TBK1 or IRF3 siRNA prevented the TWEAK-induced ISG and inflammatory gene expression while IKKε siRNA did not. In vivo, kidney IFNAR and IFNβ were increased in murine LPS and folic acid nephrotoxicity while IFNAR was increased in human kidney biopsies with tubulointerstitial damage. Inhibition of TBK1/IKKε with amlexanox or IFNAR neutralization decreased TI-IFN pathway activation and protected from kidney injury induced by folic acid or LPS. In conclusion, TI-IFNs, TWEAK, and LPS engage interrelated proinflammatory and antiviral responses in tubular cells. Moreover, inhibition of TBK1/IKKε with amlexanox, and IFNAR targeting, may protect from tubulointerstitial kidney injury.
SlMYC2 interacted with the SlTOR promoter and mediated JA signaling to regulate growth and fruit quality in tomato
Authors: Zhang Yujiao , Xing Hongyun , Wang Haoran , Yu Lan , Yang Zhi , Meng Xiangnan , Hu Pengpeng , Fan Haiyan , Yu Yang , Cui Na
Published: October 2022

Tomato (Solanum lycopersicum) is a major vegetable crop cultivated worldwide. The regulation of tomato growth and fruit quality has long been a popular research topic. MYC2 is a key regulator of the interaction between jasmonic acid (JA) signaling and other signaling pathways, and MYC2 can integrate the interaction between JA signaling and other hormone signals to regulate plant growth and development. TOR signaling is also an essential regulator of plant growth and development. However, it is unclear whether MYC2 can integrate JA signaling and TOR signaling during growth and development in tomato. Here, MeJA treatment and SlMYC2 overexpression inhibited the growth and development of tomato seedlings and photosynthesis, but increased the sugar–acid ratio and the contents of lycopene, carotenoid, soluble sugar, total phenol and flavonoids, indicating that JA signaling inhibited the growth of tomato seedlings and altered fruit quality. When TOR signaling was inhibited by RAP, the JA content increased, and the growth and photosynthesis of tomato seedlings decreased, indicating that TOR signaling positively regulated the growth and development of tomato seedlings. Further yeast one-hybrid assays showed that SlMYC2 could bind directly to the SlTOR promoter. Based on GUS staining analysis, SlMYC2 regulated the transcription of SlTOR, indicating that SlMYC2 mediated the interaction between JA and TOR signaling by acting on the promoter of SlTOR. This study provides a new strategy and some theoretical basis for tomato breeding.
Metabolomic and transcriptomic exploration of the uric acid-reducing flavonoids biosynthetic pathways in the fruit of Actinidia arguta Sieb. Zucc.
Authors: Wang Yubo , Zhang Minghui , Dong Kuiling , Yin Xiaojuan , Hao Chunhui , Zhang Wenge , Irfan Muhammad , Chen Lijing , Wang Yong
Published: October 2022

Flavonoids from Actinidia arguta Sieb. Zucc. can reduce uric acid in mice. However, the molecular basis of its biosynthesis is still unclear. In this paper, we used a combination of extensively targeted metabolomics and transcriptomics analysis to determine the types and differences of flavonoids in the fruit ripening period (August to September) of two main cultivated varieties in northern China. The ethanol extract was prepared, and the potential flavonoids of Chrysin (Flavone1), Rutin (Flavone2), and Daidzein (Flavone3) in Actinidia arguta Sieb. Zucc. were separated and purified by HPD600 macroporous adsorption resin and preparative liquid chromatography. The structure was identified by MS-HPLC, and the serum uric acid index of male Kunming mice was determined by an animal model test.125 flavonoids and 50 differentially regulated genes were identified. The contents of UA (uric acid), BUN (urea nitrogen), Cr (creatinine), and GAPDH in mouse serum and mouse liver glycogen decreased or increased in varying degrees. This paper reveals the biosynthetic pathway of uric acid-reducing flavonoids in the fruit of Actinidia arguta Sieb. Zucc., a major cultivar in northern China, provides valuable information for the development of food and drug homologous functional foods.
Mutations in the SmAPRR2 transcription factor suppressing chlorophyll pigmentation in the eggplant fruit peel are key drivers of a diversified colour palette
Authors: Arrones Andrea , Mangino Giulio , Alonso David , Plazas Mariola , Prohens Jaime , Portis Ezio , Barchi Lorenzo , Giuliano Giovanni , Vilanova Santiago , Gramazio Pietro
Published: October 2022

Understanding the mechanisms by which chlorophylls are synthesized in the eggplant (Solanum melongena) fruit peel is of great relevance for eggplant breeding. A multi-parent advanced generation inter-cross (MAGIC) population and a germplasm collection have been screened for green pigmentation in the fruit peel and used to identify candidate genes for this trait. A genome-wide association study (GWAS) performed with 420 MAGIC individuals revealed a major association on chromosome 8 close to a gene similar to APRR2. Two variants in SmAPRR2, predicted as having a high impact effect, were associated with the absence of fruit chlorophyll pigmentation in the MAGIC population, and a large deletion of 5.27 kb was found in two reference genomes of accessions without chlorophyll in the fruit peel. The validation of the candidate gene SmAPRR2 was performed by its sequencing in a set of MAGIC individuals and through its de novo assembly in 277 accessions from the G2P-SOL eggplant core collection. Two additional mutations in SmAPRR2 associated with the lack of chlorophyll were identified in the core collection set. The phylogenetic analysis of APRR2 reveals orthology within Solanaceae and suggests that specialization of APRR2-like genes occurred independently in Cucurbitaceae and Solanaceae. A strong geographical differentiation was observed in the frequency of predominant mutations in SmAPRR2, resulting in a lack of fruit chlorophyll pigmentation and suggesting that this phenotype may have arisen and been selected independently several times. This study represents the first identification of a major gene for fruit chlorophyll pigmentation in the eggplant fruit.
Exploring and applying genes to enhance the resistance to Fusarium head blight in wheat
Authors: Ma Haigang , Liu Yongjiang , Zhao Xueyan , Zhang Suhong , Ma Hongxiang
Published: October 2022

Fusarium head blight (FHB) is a destructive disease in wheat worldwide. Fusarium graminearum species complex (FGSC) is the main causal pathogen causing severe damage to wheat with reduction in both grain yield and quality. Additionally, mycotoxins produced by the FHB pathogens are hazardous to the health of human and livestock. Large numbers of genes conferring FHB resistance to date have been characterized from wheat and its relatives, and some of them have been widely used in breeding and significantly improved the resistance to FHB in wheat. However, the disease spreads rapidly and has been severe due to the climate and cropping system changes in the last decade. It is an urgent necessity to explore and apply more genes related to FHB resistant for wheat breeding. In this review, we summarized the genes with FHB resistance and mycotoxin detoxication identified from common wheat and its relatives by using forward- and reverse-genetic approaches, and introduced the effects of such genes and the genes with FHB resistant from other plant species, and host-induced gene silencing (HIGS) in enhancing the resistance to FHB in wheat. We also outlined the molecular rationale of the resistance and the application of the cloned genes for FHB control. Finally, we discussed the future challenges and opportunities in this field.
Variations in mitragynine content in the naturally growing Kratom (Mitragyna speciosa) population of Thailand
Authors: Leksungnoen Nisa , Andriyas Tushar , Ngernsaengsaruay Chatchai , Uthairatsamee Suwimon , Racharak Phruet , Sonjaroon Weerasin , Kjelgren Roger , Pearson Brian J. , McCurdy Christopher R. , Sharma Abhisheak
Published: October 2022

We analyzed the content of mitragynine (MG) found in kratom leaves (Mitragyna speciosa) and the influence of different environmental conditions (air and soil variables) on the yield in various regions of Thailand. The content of MG in kratom leaves ranged from 7.5 – 26.6 mg g-1 of dry leaf weight. Canonical correspondence analysis showed that the most significant environmental variables affecting the MG content among the various regions were light intensity, relative humidity, soil volumetric water content (VW), soil pH, and calcium. This study is a first step towards providing information about environmental conditions suitable to maximize the quality and quantity of bioactive alkaloids in kratom. Future studies should focus on leaf collection and the post-harvest processes in order to assure the desired alkaloidal content in finished products, when produced under suitable environmental conditions identified in this study.