bluuebunny/crossref_metadata_2025 huggingface dataset:
High-Mobility Group A1 Promotes Cardiac Fibrosis by Upregulating FOXO1 in Fibroblasts
Authors: Xie Qingwen , Yao Qi , Hu Tongtong , Cai Zhulan , Zhao Jinhua , Yuan Yuan , Wu Qing Qing , Tang Qi-zhu
Published: August 2021

High-mobility group A1 (HMGA1) acts as a transcription factor in several cardiovascular diseases. However, the implications of HMGA1 in cardiac fibrosis remain unknown. Here, we investigated the impact of HMGA1 on cardiac fibrosis. A mouse cardiac fibrosis model was constructed via subcutaneous injection of isoproterenol (ISO) or angiotensin II (Ang II) infusion. Adult mouse cardiac fibroblasts (CFs) were isolated and cultured. CFs were stimulated with transforming growth factor-β1 (TGF-β1) for 24 h. As a result, HMGA1 was upregulated in fibrotic hearts, as well as TGF-β-stimulated CFs. Overexpression of HMGA1 in CFs aggravated TGF-β1-induced cell activation, proliferation, and collagen synthesis. Overexpression of HMGA1 in fibroblasts, by an adeno-associated virus 9 dilution system with a periostin promoter, accelerated cardiac fibrosis and cardiac dysfunction. Moreover, HMGA1 knockdown in CFs inhibited TGF-β1-induced cell activation, proliferation, and collagen synthesis. Mechanistically, we found that HMGA1 increased the transcription of FOXO1. The FOXO1 inhibitor AS1842856 counteracted the adverse effects of HMGA1 overexpression in vitro. HMGA1 silencing in mouse hearts alleviated Ang II-induced cardiac fibrosis and dysfunction. However, FOXO1 knockdown in mouse hearts abolished the deteriorating effects of HMGA1 overexpression in mice. Collectively, our data demonstrated that HMGA1 plays a critical role in the development of cardiac fibrosis by regulating FOXO1 transcription.
Optimized Placement of Voltage Sag Monitors Considering Distributed Generation Dominated Grids and Customer Demands
Authors: Wang Ying , He Haishan , Fu Qiang , Xiao XianYong , Chen Yunzhu
Published: August 2021

Voltage sag causes serious economic losses to sensitive customers. However, the existing optimal placement methods of sag monitors ignore the economic needs of customers. The optimal placement model of voltage sag monitor is proposed in this paper, which considers the sag economic loss weight, realizes the redundant coverage of important customers, and reduces the risk of sag loss of them. The model is also suitable for the system with a large number of DG access. Firstly, the calculation model of exposed area based on Chebyshev iterative method is established to obtain the system exposed area quickly, and the influence of DG replacing traditional generator on exposed area and economic loss is analyzed qualitatively. Then, the economic loss is quantitatively evaluated based on the exposed area. What’s more, the priority of important customers is determined accordingly, and the optimal placement model of sag monitor is proposed. Finally, simulation results show that in large-scale DG access, the customer’s economic loss caused by sag will increase. Compared with traditional methods, this method can reduce the risk of loss and ensure the economic benefits of important customers.
Geographical, Climatological, and Biological Characteristics of Tree Radial Growth Response to Autumn Climate Change
Authors: Tei Shunsuke , Kotani Ayumi , Sugimoto Atsuko , Shin Nagai
Published: August 2021

Terrestrial forest ecosystems are crucial to the global carbon cycle and climate system; however, these ecosystems have experienced significant warming rates in recent decades, whose impact remains uncertain. This study investigated radial tree growth using the tree-ring width index (RWI) for forest ecosystems throughout the Northern Hemisphere to determine tree growth responses to autumn climate change, a season which remains considerably understudied compared to spring and summer, using response function and random forest machine learning methods. Results showed that autumn climate conditions significantly impact the RWI throughout the Northern Hemisphere. Spatial variations in the RWI response were influenced by geography (latitude, longitude, and elevation), climatology, and biology (tree genera); however, geographical and/or climatological characteristics explained more of the response compared to biological characteristics. Higher autumn temperatures tended to negatively impact tree radial growth south of 40° N in regions of western Asia, southern Europe, United State of America and Mexico, which was similar to the summer temperature response found in previous studies, which was attributed to temperature-induced water stress.
A Prognostic Signature Constructed by CTHRC1 and LRFN4 in Stomach Adenocarcinoma
Authors: Han Songling , Zhu Wei , Yang Weili , Guan Qijie , Chen Chao , He Qiang , Zhong Zhuoheng , Zhao Ruoke , Xiong Hangming , Han Haote , Li Yaohan , Sun Zijian , Hu Xingjiang , Tian Jingkui
Published: August 2021

Background

Stomach adenocarcinoma (STAD) is the most common histological type of stomach cancer, which causes a considerable number of deaths worldwide. This study aimed to identify its potential biomarkers with the notion of revealing the underlying molecular mechanisms.

Methods

Gene expression profile microarray data were downloaded from the Gene Expression Omnibus (GEO) database. The “limma” R package was used to screen the differentially expressed genes (DEGs) between STAD and matched normal tissues. The Database for Annotation, Visualization, and Integrated Discovery (DAVID) was used for function enrichment analyses of DEGs. The STAD dataset from The Cancer Genome Atlas (TCGA) database was used to identify a prognostic gene signature, which was verified in another STAD dataset from the GEO database. CIBERSORT algorithm was used to characterize the 22 human immune cell compositions. The expression of LRFN4 and CTHRC1 in tissues was determined by quantitative real-time PCR from the patients recruited to the present study.

Results

Three public datasets including 90 STAD patients and 43 healthy controls were analyzed, from which 44 genes were differentially expressed in all three datasets. These genes were implicated in biological processes including cell adhesion, wound healing, and extracellular matrix organization. Five out of 44 genes showed significant survival differences. Among them, CTHRC1 and LRFN4 were selected for construction of prognostic signature by univariate Cox regression and stepwise multivariate Cox regression in the TCGA-STAD dataset. The fidelity of the signature was evaluated in another independent dataset and showed a good classification effect. The infiltration levels of multiple immune cells between high-risk and low-risk groups had significant differences, as well as two immune checkpoints. TIM-3 and PD-L2 were highly correlated with the risk score. Multiple signaling pathways differed between the two groups of patients. At the same time, the expression level of LRFN4 and CTHRC1 in tissues analyzed by quantitative real-time PCR were consistent with the in silico findings.

Conclusion

The present study constructed the prognostic signature by expression of CTHRC1 and LRFN4 for the first time via comprehensive bioinformatics analysis, which provided the potential therapeutic targets of STAD for clinical treatment.
Identification of Potential Biomarkers for Psoriasis by DNA Methylation and Gene Expression Datasets
Authors: Liu Yong , Cui Shengnan , Sun Jiayi , Yan Xiaoning , Han Dongran
Published: August 2021

DNA methylation (DNAm) plays an important role in the pathogenesis of psoriasis through regulating mRNA expressions. This study aimed to identify hub genes regulated by DNAm as biomarkers of psoriasis. Psoriatic skin tissues gene expression and methylation datasets were downloaded from Gene Expression Omnibus (GEO) database. Subsequently, multiple computational approaches, including immune infiltration analysis, enrichment analysis, protein–protein interaction (PPI) network establishment, and machine learning algorithm analysis (lasso, random forest, and SVM-RFE), were performed to analyze the regulatory networks, to recognize hub genes, and to clarify the pathogenesis of psoriasis. Finally, the hypermethylated genes were used to immune cell infiltration analysis, which revealed that psoriasis skin tissues were mainly composed of activated dendritic cells, resting mast cells, T follicular helper cells (cTfh), etc. Differentially expressed-methylated genes (DEMGs) were identified and partitioned into four subgroups and the 97 significantly hypermethylated and downregulated (hyper-down) genes accounted for the highest proportion (47%). Hyper-down genes were mainly enriched in glucose homeostasis, AMP-activated protein kinase (AMPK) signaling pathway, lipid storage disease, partial lipodystrophy, and insulin resistance. Furthermore, insulin receptor substrate 1 (IRS1), Rho guanine nucleotide exchange factor 10 (ARHGEF10) and retinoic acid induced 14 (RAI14) were identified as potential targets. These findings provided new ideas for future studies of psoriasis on the occurrence and the molecular mechanisms.
The Role of the Adhesion Receptor CD146 and Its Soluble Form in Human Embryo Implantation and Pregnancy
Authors: Bouvier Sylvie , Kaspi Elise , Joshkon Ahmad , Paulmyer-Lacroix Odile , Piercecchi-Marti Marie-Dominique , Sharma Akshita , Leroyer Aurélie S. , Bertaud Alexandrine , Gris Jean-Christophe , Dignat-George Françoise , Blot-Chabaud Marcel , Bardin Nathalie
Published: August 2021

CD146 is an adhesion molecule essentially located in the vascular system, which has been described to play an important role in angiogenesis. A soluble form of CD146, called sCD146, is detected in the bloodstream and is known as an angiogenic factor. During placental development, CD146 is selectively expressed in extravillous trophoblasts. A growing body of evidence shows that CD146 and, in particular, sCD146, regulate extravillous trophoblasts migration and invasion both in vitro and in vivo. Hereby, we review expression and functions of CD146/sCD146 in the obstetrical field, mainly in pregnancy and in embryo implantation. We emphasized the relevance of quantifying sCD146 in the plasma of pregnant women or in embryo supernatant in the case of in vitro fertilization (IVF) to predict pathological pregnancy such as preeclampsia or implantation defect. This review will also shed light on some major results that led us to define CD146/sCD146 as a biomarker of placental development and paves the way toward identification of new therapeutic targets during implantation and pregnancy.
Follicular Helper T (TFH) Cell Targeting by TLR8 Signaling For Improving HBsAg-Specific B Cell Response In Chronic Hepatitis B Patients
Authors: Ayithan Natarajan , Tang Lydia , Tan Susanna K. , Chen Diana , Wallin Jeffrey J. , Fletcher Simon P. , Kottilil Shyam , Poonia Bhawna
Published: August 2021

Identifying signaling pathways that induce B cell response can aid functional cure strategies for chronic hepatitis B infection (CHB). TLR8 activation with ssRNA was shown to enhance follicular helper T cell (TFH) function leading to improved B cell responses in vitro. We investigated whether this mechanism can rescue an exhausted immune response in CHB infection. Effect of TLR8 agonism on supporting cytokines and TFH and B cells were evaluated using ex vivo and in vitro assays. The ability of an oral TLR8 agonist to promote TFH and B cell response was tested in samples from phase 1b clinical trial. TLR8 agonism induced TFH polarizing cytokine IL-12 in monocytes. Treatment of peripheral blood mononuclear cells (PBMCs) from CHB patients with TLR8 agonists induced cytokine IL-21 by TFH cells with enhanced IL-21+BCL-6+ and ICOS+BCL-6+ co-expression. Mechanistically, incubation of isolated naïve CD4+ T cells with TLR8 triggered monocytes resulted in their differentiation into IL-21+ICOS+BCL-6+ TFH in an IL-12 dependent manner. Furthermore, co-culture of these IL-21 producing TFH with autologous naïve B cells led to enhanced memory (CD19+CD27+) and plasma B cell generation (CD19+CD27++CD38+) and IgG production. Importantly, in TFH from CHB patients treated with an oral TLR8 agonist, HBsAg-specific BCL-6, ICOS, IL-21 and CD40L expression and rescue of defective activation induced marker (AIM) response along with partial restoration of HBsAg-specific B cell ELISPOT response was evident. TLR8 agonism can thus enhance HBV-specific B cell responses in CHB patients by improving monocyte-mediated TFH function and may play a role in achieving HBV functional cure.
Listeria monocytogenes Contamination Characteristics in Two Ready-to-Eat Meat Plants From 2019 to 2020 in Shanghai
Authors: Zhang Hongzhi , Wang Jing , Chang Zhaoyu , Liu Xin , Chen Weijie , Yu Ying , Wang Xiaoguang , Dong Qingli , Ye Yulong , Zhang Xi
Published: August 2021

Listeria monocytogenes is a ubiquitous foodborne pathogen that causes listeriosis and is mostly linked to consumption of ready-to-eat (RTE) foods. Lack of hygiene in food processing environments may be a primary reason for contamination by L. monocytogenes isolates. In this study, L. monocytogenes strains isolated from two RTE meat processing plants in the Shanghai municipality, China, were characterized during 2019–2020 using pulsed-field gel electrophoresis and whole-genome sequencing. Results showed that 29 samples (12.2%) out of 239 were positive for L. monocytogenes, with 21 (18.9%) and 8 (6.25%) isolates from plants A and B, respectively. The packaging room at plant A had the most contamination (14, 48.3%; p < 0.05), with a peak occurrence of 76.5% in processing environments. Nineteen L. monocytogenes isolates belonging to the pulsotype (PT) 7 group were indistinguishable (≥ 95.7%). Furthermore, core-genome multiple loci sequencing typing identified up to nine allelic differences, and the closet pairwise differences among these ST5 isolates included 0–16 small nucleotide polymorphisms. Therefore, L. monocytogenes likely persisted at plant A during 2019–2020 with ongoing clone transmission. In contrast, no L. monocytogenes isolates were identified from processing environments at plant B. Most L. monocytogenes isolates were sampled from raw materials (62.5%). Several isolates (ST378, ST8, and ST120) were detected only once in 2020 and were considered as transient isolates. However, three ST121 isolates with the same PT (PT2) were detected in 2020 and should be noted for their stronger survival ability in harsh environments. These results suggest that continuous monitoring, stringent surveillance, and source tracking are crucial to guaranteeing food safety in RTE food plants.
Altered Fecal Microbiome and Metabolome in a Mouse Model of Choroidal Neovascularization
Authors: Li Yun , Cai Yuting , Huang Qian , Tan Wei , Li Bingyan , Zhou Haixiang , Wang Zicong , Zou Jingling , Ding Chun , Jiang Bing , Yoshida Shigeo , Zhou Yedi
Published: August 2021

Purpose

Choroidal neovascularization (CNV) is the defining feature of neovascular age-related macular degeneration (nAMD). Gut microbiota might be deeply involved in the pathogenesis of nAMD. This study aimed to reveal the roles of the gut microbiome and fecal metabolome in a mouse model of laser-induced CNV.

Methods

The feces of C57BL/6J mice with or without laser-induced CNV were collected. Multi-omics analyses, including 16S rRNA gene sequencing and untargeted metabolomics, were conducted to analyze the changes in the gut microbial composition and the fecal metabolomic profiles in CNV mice.

Results

The gut microbiota was significantly altered in CNV mice. The abundance of Candidatus_Saccharimonas was significantly upregulated in the feces of CNV mice, while 16 genera, including Prevotellaceae_NK3B31_group, Candidatus_Soleaferrea, and Truepera, were significantly more abundant in the controls than in the CNV group. Fecal metabolomics identified 73 altered metabolites (including 52 strongly significantly altered metabolites) in CNV mice compared to control mice. Correlation analysis indicated significant correlations between the altered fecal metabolites and gut microbiota genera, such as Lachnospiraceae_UCG-001 and Candidatus_Saccharimonas. Moreover, KEGG analysis revealed six pathways associated with these altered metabolites, such as the ABC transporter, primary bile acid biosynthesis and steroid hormone biosynthesis pathways.

Conclusion

The study identified an altered fecal microbiome and metabolome in a CNV mouse model. The altered microbes, metabolites and the involved pathways might be associated with the pathogenesis of nAMD.
Perforating Arteries of the Lemniscal Trigone: A Microsurgical Neuroanatomic Description
Authors: Tomasi Santino Ottavio , Umana Giuseppe Emmanuele , Scalia Gianluca , Rubio-Rodriguez Roberto Luis , Raudino Giuseppe , Rechberger Julian , Geiger Philipp , Chaurasia Bipin , Yaǧmurlu Kaan , Lawton Michael T. , Winkler Peter A.
Published: August 2021

Background: The perforating arteries in the dorsolateral zone of the midbrain play a crucial role in the functions of the brain stem. Their damage due to herniation, pathological lesions, or surgery, favored by the narrow tentorial incisura, can lead to hemorrhages or ischemia and subsequently to severe consequences for the patient.

Objective: In literature, not much attention has been directed to the perforating arteries in the lemniscus; in fact, no reports on the perforators of this anatomical region are available. The present study aims to a detailed analysis of the microanatomy and the clinical implications of these perforators, in relation to the parent vessels. We focused on the small vessels that penetrate the midbrain's dorsolateral surface, known as lemniscal trigone, to understand better their microanatomy and their functional importance in the clinical practice during the microsurgical approach to this area.

Methods: Eighty-seven alcohol-fixed cadaveric hemispheres (44 brains) without any pathological lesions provided the material for studying the perforating vessels and their origin around the dorsolateral midbrain using an operating microscope (OPMI 1 FC, Zeiss). Measurements of the perforators' distances, in relation to the parent vessels, were taken using a digital caliper.

Results: An origin from the SCA could be found in 70.11% (61) and from the PCA in 27.58% (24) of the hemispheres. In one hemisphere, an origin from the posterior choroidal artery was found (4.54%). No perforating branches were discovered in 8.04% of specimens (7).

Conclusion: The perforating arteries of the lemniscal trigone stem not only from the superior cerebellar artery (SCA), as described in the few studies available in literature, but also from the posterior cerebral artery (PCA). Therefore, special attention should be paid during surgery to spare those vessels and associated perforators. A comprehensive understanding of the lemniscal trigone's perforating arteries is vital to avoid infarction of the brainstem when treating midbrain tumors or vascular malformations.
Clinical Features of Coexisting Anti-NMDAR and MOG Antibody-Associated Encephalitis: A Systematic Review and Meta-Analysis
Authors: Ding Jiayue , Li Xiangyu , Tian Zhiyan
Published: August 2021

Coexisting anti-NMDAR and MOG antibody (anti-NMDAR-IgG+/MOG-IgG+)-associated encephalitis have garnered great attention. This study aimed to perform a secondary analysis to determine the clinical features of this disease. We searched several databases for related publications published prior to April 2021. A pooled analysis was conducted with the fixed-effects model using the Mante-Haenszel method (I2 ≤ 50%), or the random-effects model computed by the DerSimonian–Laird method (I2 > 50%). Stata software (version 15.0 SE) was used for the analyses. Nine observational studies and 16 case reports (58 cases with anti-NMDAR-IgG+/MOG-IgG+, 21.0 [8.5, 29.0] years, male 58.6%) were included. The incidences (95%CI) of anti-NMDAR-IgG+/MOG-IgG+ in the patients with serum MOG-IgG+ and CSF anti-NMDAR-IgG+ were 0.09 (0.02–0.19) and 0.07 (0.01–0.19), respectively. The median [IQR] of CSF anti-NMDAR antibody titer was 32 [10, 100], and the serum anti-MOG antibody titer was 100 [32, 320]. The prominent clinical symptoms were encephalitic manifestations, including seizures (56.9%) and abnormal behavior (51.7%), rather than demyelinating manifestations, such as speech disorder (34.5%) and optic neuritis (27.6%). Relapse occurred in 63.4% of anti-NMDAR-IgG+/MOG-IgG+ patients, in whom 50.0% of cases relapsed with encephalitic manifestations, and 53.8% relapsed with demyelinating manifestations. The common MRI changes were in the cortex or subcortex (70.7%) and brainstem (31.0%). 31.3% of patients presented with unilateral cerebral cortical encephalitis with epilepsy and 12.5% displayed bilateral frontal cerebral cortex encephalitis. Anti-NMDAR-IgG+/MOG-IgG+ patients showed more frequent mental behavior (OR, 95%CI, 68.38, 1.36–3,434.37), involuntary movement (57.86, 2.53–1,325.11), sleep disorders (195.00, 7.07–5,380.15), and leptomeninge lesions (7.32, 1.81–29.58), and less frequent optic neuritis (0.27, 0.09–0.83) compared to anti-NMDAR-IgG−/MOG-IgG+ patients and presented more common relapse (5.63, 1.75–18.09), preceding infection (2.69, 1.03–7.02), subcortical lesions (116.60, 4.89–2,782.09), basal ganglia lesions (68.14, 2.99–1,554.27), brainstem lesions (24.09, 1.01–574.81), and spinal cord lesions (24.09, 1.01–574.81) compared to anti-NMDAR-IgG+/MOG-IgG−. In conclusion, anti-NMDAR-IgG+/MOG-IgG+ was rarely observed, but the incidence rate of relapse was very high. The overall symptoms seemed to be similar to those of NMDAR encephalitis.
Deconstructing Apathy in Parkinson's Disease: Challenges in Isolating Core Components of Apathy From Depression, Anxiety, and Fatigue
Authors: Ineichen Christian , Baumann-Vogel Heide
Published: August 2021

Apathy, fatigue and depression are amongst the most debilitating non-motor syndromes of Parkinson's disease (PD). The aim of this study was to examine the prevalence of apathy, depression, anxiety and fatigue and whether these syndromes are separable in PD. A total of 337 patients were examined using the Unified Parkinson's Disease Rating Scale (UPDRS part III), the Apathy Evaluation Scale, the Hospital Anxiety and Depression Scale and the Fatigue Severity Scale. Using standard cutoff criteria, the prevalence rates of significant apathy, mild-to-severe depression, mild-to-severe anxiety and severe fatigue were 23.7, 13.4, 15.4, and 17.8%, respectively. Next, confirmatory factor analysis was employed of items from these three clinical scales. A priori hypothesis testing including four different factors (reduced motivation/interest, physical fatigue, reduced pleasure, anxiety) was performed. The factor analysis revealed strong fit statistics for the model with χ2 (57, N = 377) = 58.9, p = 0.41, CMIN/DF = 1,034, NFI = 0.977, CFI = 0.999, IFI = 0.999, RFI = 0.968, and TLI = 0.999. The RMSEA was 0.01, and the standardized RMR was 0.027. These results support the hypothesis that apathy, fatigue, depression and anxiety represent prevalent syndromes that can be separated in Parkinson's disease and that apathy is not just a subcomponent of depression or fatigue. The results of this study may contribute to a clearer diagnostic process for apathy, fatigue and depression and may aid in patient care.
Association Between Dietary Quality and Postpartum Depression in Lactating Women: A Cross-Sectional Survey in Urban China
Authors: Yang Chenlu , Zhao Ai , Lan Hanglian , Ren Zhongxia , Zhang Jian , Szeto Ignatius Man-Yau , Wang Peiyu , Zhang Yumei
Published: August 2021

Background: Evidence on the effects of dietary quality on the risk of postpartum depression in the Chinese population is limited. This study aimed to examine the association between dietary quality and postpartum depression in Chinses lactating women.

Methods: A total of 939 participants from 10 cities were included in this analysis. A one-time 24-h dietary recall was used to obtain the data on food consumption and dietary quality was assessed based on Diet Balance Index. The Edinburgh postnatal depression scale was considered at a cutoff point of 10 to detect postpartum depression. Poisson regression models were used to explore the association of dietary quality with postpartum depression.

Results: Depressed women tended to have a more inadequate intake of vegetables and have more insufficient food variety. The median (25th, 75th) of the overall high bound score (HBS), low bound score (LBS), and diet quality distance (DQD) was 9 (5, 14), 30 (25, 37), and 40 (34, 47), respectively. Compared with subjects with the lowest quartile of LBS, those with the highest quartile of LBS had a higher risk of postpartum depression [adjusted prevalence ratio (aPR), 1.08; 95% confidence interval (95% CI), 1.01, 1.15; P for trend, 0.043]. We also observed a significant association between DQD and postpartum depression (Q4 vs. Q1: aPR, 1.07; 95% CI: 1.00, 1.14; P for trend, 0.036).

Conclusion: Poor dietary quality was associated with postpartum depression in Chinese lactating women.
The Origins and Generation of Cancer-Associated Mesenchymal Stromal Cells: An Innovative Therapeutic Target for Solid Tumors
Authors: Li Wei , Yang Jin , Zheng Ping , Li Haining , Zhao Shaolin
Published: August 2021

Cancer-associated mesenchymal stromal cells (CA-MSCs) have been isolated from various types of tumors and are characterized by their vigorous pro-tumorigenic functions. However, very little is known about the origins and generating process of CA-MSCs, which may facilitate the identification of biomarkers for diagnosis or innovative targets for anti-cancer therapy to restrain the tumor growth, spread and chemotherapy resistance. Current evidences have indicated that both distally recruited and local resident MSCs are the primary origins of CA-MSCs. In a tissue type-dependent mode, tumor cells together with the TME components prompt the malignant transition of tumor “naïve” MSCs into CA-MSCs in a direct cell-to-cell contact, paracrine or exosome-mediated manner. In this review, we discuss the transition of phenotypes and functions of naïve MSCs into CA-MSCs influenced by tumor cells or non-tumor cells in the TME. The key areas remaining poorly understood are also highlighted and concluded herein.
Prognostic Factors for Overall Survival In Chronic Myeloid Leukemia Patients: A Multicentric Cohort Study by the Italian CML GIMEMA Network
Authors: Specchia Giorgina , Pregno Patrizia , Breccia Massimo , Castagnetti Fausto , Monagheddu Chiara , Bonifacio Massimiliano , Tiribelli Mario , Stagno Fabio , Caocci Giovanni , Martino Bruno , Luciano Luigiana , Pizzuti Michele , Gozzini Antonella , Scortechini Anna Rita , Albano Francesco , Bergamaschi Micaela , Capodanno Isabella , Patriarca Andrea , Fava Carmen , Rege-Cambrin Giovanna , Sorà Federica , Galimberti Sara , Bocchia Monica , Binotto Gianni , Reddiconto Giovanni , DiTonno Paolo , Maggi Alessandro , Sanpaolo Grazia , De Candia Maria Stella , Giai Valentina , Abruzzese Elisabetta , Miggiano Maria Cristina , La Barba Gaetano , Pietrantuono Giuseppe , Guella Anna , Levato Luciano , Mulas Olga , Saccona Fabio , Rosti Gianantonio , Musto Pellegrino , Di Raimondo Francesco , Pane Fabrizio , Baccarani Michele , Saglio Giuseppe , Ciccone Giovannino
Published: August 2021

An observational prospective study was conducted by the CML Italian network to analyze the role of baseline patient characteristics and first line treatments on overall survival and CML-related mortality in 1206 newly diagnosed CML patients, 608 treated with imatinib (IMA) and 598 with 2nd generation tyrosine kinase inhibitors (2GTKI). IMA-treated patients were much older (median age 69 years, IQR 58-77) than the 2GTKI group (52, IQR 41-63) and had more comorbidities. Estimated 4-year overall survival of the entire cohort was 89% (95%CI 85.9-91.4). Overall, 73 patients (6.1%) died: 17 (2.8%) in the 2GTKI vs 56 (9.2%) in the IMA cohort (adjusted HR=0.50; 95% CI=0.26-0.94), but no differences were detected for CML-related mortality (10 (1.7%) vs 11 (1.8%) in the 2GTKIs vs IMA cohort (sHR=1.61; 0.52-4.96). The ELTS score was associated to CML mortality (high risk vs low, HR=9.67; 95%CI 2.94-31.74; p<0.001), while age (per year, HR=1.03; 95%CI 1.00-1.06; p=0.064), CCI (4-5 vs 2, HR=5.22; 95%CI 2.56-10.65; p<0.001), ELTS score (high risk vs low, HR=3.11; 95%CI 1.52-6.35, p=0.002) and 2GTKI vs IMA (HR=0.26; 95%CI 0.10-0.65, p=0.004) were associated to an increased risk of non-related CML mortality. The ELTS score showed a better discriminant ability than the Sokal score in all comparisons.
Towards Building a Quantitative Proteomics Toolbox in Precision Medicine: A Mini-Review
Authors: Correa Rojo Alejandro , Heylen Dries , Aerts Jan , Thas Olivier , Hooyberghs Jef , Ertaylan Gökhan , Valkenborg Dirk
Published: August 2021

Precision medicine as a framework for disease diagnosis, treatment, and prevention at the molecular level has entered clinical practice. From the start, genetics has been an indispensable tool to understand and stratify the biology of chronic and complex diseases in precision medicine. However, with the advances in biomedical and omics technologies, quantitative proteomics is emerging as a powerful technology complementing genetics. Quantitative proteomics provide insight about the dynamic behaviour of proteins as they represent intermediate phenotypes. They provide direct biological insights into physiological patterns, while genetics accounting for baseline characteristics. Additionally, it opens a wide range of applications in clinical diagnostics, treatment stratification, and drug discovery. In this mini-review, we discuss the current status of quantitative proteomics in precision medicine including the available technologies and common methods to analyze quantitative proteomics data. Furthermore, we highlight the current challenges to put quantitative proteomics into clinical settings and provide a perspective to integrate proteomics data with genomics data for future applications in precision medicine.
Predictors in ASD: The Importance of Parents' Perception
Authors: Mira Coelho Alda , da Conceição Virgínia
Published: August 2021

Several predictors may influence children's developmental trajectories with Autism Spectrum Disorder (ASD), and parents' concerns may play an important role. This study aimed to investigate developmental trajectories of two groups of children with ASD to understand predictive factors, including parental perception. We examined the clinical features of a sample of 55 children with ASD at 3 and 6 years of age in two moments of evaluation to understand this process. We used the Autism Diagnostic Observation Schedule, (ADOS) in both moments. We selected two groups based on ADOS results at moment two: one group with a worse outcome (ADOS results above 8) and one group with a better outcome (ADOS results below 8 in the second moment). We also selected questions from a questionnaire (elaborated by the authors and used in clinical practice) applied to parents to understand if early parents' concerns may help to predict ASD prognosis. We found a significant association between imitation and playability and the child's prognostic. Also, Interactive Gestures, Beginning of Joint Attention, Reciprocity, and Pleasure in Interaction might help identify positive case evolution. Our findings are significant in early intervention program development, not only with direct intervention with the child but also including the parents' involvement in the intervention.
Role of Climate-Smart Agriculture in Enhancing Farmers' Livelihoods and Sustainable Forest Management: A Case of Villages Around Songe-Bokwa Forest, Kilindi District, Tanzania
Authors: Nkumulwa Hamza Omary , Pauline Noah Makula
Published: August 2021

Climate change and variability are happening in Tanzania, and their impacts are felt in the socioeconomic sectors, as they have resulted in the decline of agricultural productivity and increased deforestation. This study assessed the actual changes in deforestation levels and improved livelihoods caused by the adoption of climate-smart agriculture (CSA) practices. Data were collected through semi-structured household questionnaires, focus group discussions, key informants, GIS tools, and observations. Quantitative data were analyzed using Arc GIS 10.3 software, SPSS version 16.0, and Excel Spreadsheet, while qualitative data were analyzed through content analysis techniques. The findings show that farmers' livelihoods have improved and also deforestation levels decreased as a result of increased adoption of CSA during the past 30 years. Deforestation levels have been reduced from 64.6 ha per year during 1985–1995 to 11.8 ha per year during 1995–2005 and to 10.4 ha per year during 2005–2017. Further findings showed that the agricultural area had been decreased from 4,534 ha in 1995 to 4,039 ha in 2017, which is evidence that after the scale-up of CSA from the year 1992, agricultural practices were not contributing much to deforestation, while increased crop production and income were observed, which in turn supported farmers in enhancing food security, purchasing production tools, livestock, and payment for medical services, school fees, and construction of modern houses. We found that adoption of CSA systems such as agroforestry (i.e., agrisilviculture) is very crucial for improving farmer's livelihoods and reducing deforestation. Therefore, farmers need close mentoring on climate-resilient agroforestry systems, such as agrisilviculture.
Food Security and Coping Strategies of Rural Household Livelihoods to Climate Change in the Eastern Cape of South Africa
Authors: Amoah Laura Novienyo Abla , Simatele Mulala Danny
Published: August 2021

Although governments across the globe have pledged resources and efforts to minimise the factors contributing to climate change, it is a concern that climate change continues to exert significant hardship on many rural communities of which South Africa is no exception. The Eastern Cape Province in South Africa is one of the driest provinces with prolonged water scarcity challenges. The purpose of this study is to investigate coping strategies adopted by the rural poor to build resilience against food insecurity. Primary data was collected from a total of 385 respondents in three rural communities using semi-structured questionnaires and interview. The findings suggest that farmers have been proactive in responding to climate change and food security. The study revealed that farmers are engaged in different coping strategies to ensure that there is enough food for the household. Although some of the coping strategies might assist, others would have severe consequences on the health of the population, especially children. Based on the findings, it is recommended that there should be regular engagement by the local municipality, the community and rural farmers on climate change events. The focus should be on the management of drought, heatwaves, flood, and soil erosion. The government within the local municipality should also focus on building a dam for rural farmers. The dam will serve as a reservoir of water for irrigation during drought.
Collective Rural Women Access, Use, and Control Over Communal Land in Mexico: A Post-capitalist Feminist Political Ecology Approach
Authors: Soto-Alarcón Jozelin María , González-Gómez Diana Xóchitl
Published: August 2021

Rural women's access to land is fundamental for their individual and household well-being, equity, and empowerment. In Mexico, the agrarian reform of 1992 and customary gendered rights shaped land use, access, and control. Rural women's access to collective land is relevant since social property—ejidoandagrarian communities—represents 52% of the national territory. As an expression of the collective organization, commons were also performed to use and control communal land and biophysical resources collectively. This paper examines the collective peasant women's bargaining process to access, use, and control communal land. The post-capitalist feminist political ecology approach allowed us to distinguish and analyze gendered strategies employed by a cooperative led by women at different levels—household, community, and government—to access and use communal land and biophysical resources by the process of commons—commoning. Rural women's collective efforts are located in Hidalgo, central Mexico. Firstly, the Agrarian Reform modifications related to gender equality issues are investigated, followed by examining rural women's socioeconomic conditions. The case study permitted us to identify and analyze critical factors that enhanced long-term agreements to control communal land beyond the Agrarian Law scope by the commoning examination. The collective rural women's strategies to use communal land improved well-being based on gendered peasant knowledge, organization, and stakeholder support. Nevertheless, the strategies increased women's burden and reinforced the existing gendered norms such as female altruism. Furthermore, the need to discuss the bargaining process over communal land concerning a diversity of commons is argued: knowledge, social, and biophysical, in which gender and care are critical variables.
Organic Food Needs More Land and Direct Energy to Be Produced Compared to Food from Conventional Farming: Empirical Evidence from the Czech Republic
Authors: Redlichová Radka , Chmelíková Gabriela , Blažková Ivana , Svobodová Eliška , Vanderpuje Inez Naaki
Published: August 2021

This study investigated direct energy consumption and land performance under two different methods of farming—organic and conventional. The aim of our study was to examine the performance of farmers in the Czech Republic and identify the differences between organic and conventional farming regarding food safety and direct energy consumption. Based on the data from the Farm Accountancy Data Network of the EU, we measured the performance of both organic and conventional farmers in terms of product per unit of land and direct energy consumption per unit of product regarding the natural condition of the farm localization. Our findings show that organic farms produce lower output with less direct energy per unit of land; however, they need more direct energy for one unit of production. We found that a product from organic agriculture consumes 1.7-fold greater direct energy than a conventional product. The worse the natural conditions for farming, the broader the difference between organic and conventional regimes regarding their performance and energy consumption. Our conclusions may help shape agricultural policy in the Czech Republic, where organic farming is receiving systematic political support, leading to an increase in the proportion of organically farmed arable land.
Choosing the Right Therapy for Patients with Relapsed/Refractory Multiple Myeloma (RRMM) in Consideration of Patient-, Disease- and Treatment-Related Factors
Authors: Gengenbach Laura , Graziani Giulia , Reinhardt Heike , Rösner Amelie , Braun Magdalena , Möller Mandy-Deborah , Greil Christine , Wäsch Ralph , Engelhardt Monika
Published: August 2021

Treatment of relapsed/refractory multiple myeloma (RRMM) is more complex today due to the availability of novel therapeutic options, mostly applied as combination regimens. immunotherapy options have especially increased substantially, likewise the understanding that patient-, disease- and treatment-related factors should be considered at all stages of the disease. RRMM is based on definitions of the international myeloma working group (IMWG) and includes biochemical progression, such as paraprotein increase, or symptomatic relapse with CRAB criteria (hypercalcemia, renal impairment, anemia, bone lesions). When choosing RRMM-treatment, the biochemical markers for progression and severity of the disease, dynamic of disease relapse, type and number of prior therapy lines, including toxicity and underlying health status, need to be considered, and shared decision making should be pursued. Objectively characterizing health status via geriatric assessment (GA) at each multiple myeloma (MM) treatment decision point has been shown to be a better estimate than via age and comorbidities alone. The well-established national comprehensive cancer network, IMWG, European myeloma network and other national treatment algorithms consider these issues. Ideally, GA-based clinical trials should be supported in the future to choose wisely and efficaciously from available intervention and treatment options in often-older MM adults in order to further improve morbidity and mortality.
68Ga-DOTATATE PET/CT and MRI with Diffusion-Weighted Imaging (DWI) in Short- and Long-Term Assessment of Tumor Response of Neuroendocrine Liver Metastases (NELM) Following Transarterial Radioembolization (TARE)
Authors: Ingenerf Maria , Kiesl Sophia , Karim Salma , Beyer Leonie , Ilhan Harun , Rübenthaler Johannes , Seidensticker Max , Ricke Jens , Schmid-Tannwald Christine
Published: August 2021

The aim of this study was to evaluate the role of SUV and ADC in assessing early response in patients with NELM following TARE. Thirty-two patients with pre- and postinterventional MRI with DWI and 68Ga-DOTATATE PET/CT were included. ADC and SUV of three target lesions and of tumor-free spleen and liver tissue were determined on baseline and first follow-up imaging, and tumor to spleen (T/S) and tumor to liver (T/L) ratios were calculated. Response was assessed by RECIST 1.1 and mRECIST on first follow-up, and long-term response was defined as hepatic progression-free survival (HPFS) over 6, 12, and <24 months. In responders, intralesional ADC values increased and SUV decreased significantly regardless of standard of reference for response assessment (mRECIST/RECIST/HPFS > 6/12/24 m). Using ROC analysis, ΔSUV T/S ratio (max/max) and ΔSUV T/L ratio (max/mean) were found to be the best and most robust metrics to correlate with longer HPFS and were superior to ΔADC. ΔT/S ratio (max/max) < 23% was identified as an optimal cut-off to discriminate patients with longer HPFS (30.2 m vs. 13.4 m; p = 0.0002). In conclusion, early percentage changes in SUV tumor-to-organ ratios on first follow-up seem to represent a prognostic marker for longer HPFS and may help in assessing therapeutic strategies.
Efficacy and Safety of Neoadjuvant Gemcitabine Plus Nab-Paclitaxel in Borderline Resectable and Locally Advanced Pancreatic Cancer—A Systematic Review and Meta-Analysis
Authors: Damm Marko , Efremov Ljupcho , Birnbach Benedikt , Terrero Gretel , Kleeff Jörg , Mikolajczyk Rafael , Rosendahl Jonas , Michl Patrick , Krug Sebastian
Published: August 2021

Therapy with gemcitabine and nab-paclitaxel (GNP) is the most commonly used palliative chemotherapy, but its advantage in the neoadjuvant setting remains unclear. Accordingly, our aim is to evaluate the impact of first-line neoadjuvant therapy with GNP in patients with borderline resectable (BRPC) and locally advanced pancreatic cancer (LAPC). A systematic search for published studies until August 2020 was performed. The primary endpoint included resection and R0 resection rates in the intention-to-treat population. Secondary endpoints were response rate, survival and toxicity. Among 21 studies, 950 patients who received neoadjuvant GNP were evaluated. Treatment with GNP resulted in surgical resection and R0 resection rates as follows: 49% (95% CI 30–68%) and 36% (95% CI 17–58%) for BRPC and 16% (95% CI 7–26%) and 11% (95% CI 5–19%) for LAPC, respectively. The objective response rates and the median overall survival (mOS) ranged from 0 to 67% and 12 to 30 months, respectively. Neutropenia (range 5–77%) and neuropathy (range 0–22%) were the most commonly reported grade 3 to 4 adverse events. Neoadjuvant chemotherapy with GNP can be performed safely and with valuable effects in patients with BRPC and LAPC. The utility of GNP in comparison to FOLFIRINOX in the neoadjuvant setting requires further investigation in prospective randomized trials.
Emerging Role of Chimeric RNAs in Cell Plasticity and Adaptive Evolution of Cancer Cells
Authors: Mukherjee Sumit , Heng Henry H. , Frenkel-Morgenstern Milana
Published: August 2021

Gene fusions can give rise to somatic alterations in cancers. Fusion genes have the potential to create chimeric RNAs, which can generate the phenotypic diversity of cancer cells, and could be associated with novel molecular functions related to cancer cell survival and proliferation. The expression of chimeric RNAs in cancer cells might impact diverse cancer-related functions, including loss of apoptosis and cancer cell plasticity, and promote oncogenesis. Due to their recurrence in cancers and functional association with oncogenic processes, chimeric RNAs are considered biomarkers for cancer diagnosis. Several recent studies demonstrated that chimeric RNAs could lead to the generation of new functionality for the resistance of cancer cells against drug therapy. Therefore, targeting chimeric RNAs in drug resistance cancer could be useful for developing precision medicine. So, understanding the functional impact of chimeric RNAs in cancer cells from an evolutionary perspective will be helpful to elucidate cancer evolution, which could provide a new insight to design more effective therapies for cancer patients in a personalized manner.
Long-Term Prognostic Value of the Response to Therapy Assessed by Laboratory and Imaging Findings in Patients with Differentiated Thyroid Cancer
Authors: Klain Michele , Zampella Emilia , Piscopo Leandra , Volpe Fabio , Manganelli Mariarosaria , Masone Stefania , Pace Leonardo , Salvatore Domenico , Schlumberger Martin , Cuocolo Alberto
Published: August 2021

This study assessed the long-term predictive value of the response to therapy, evaluated by serum thyroglobulin (Tg) determination and neck ultrasound, and estimated the potential additional impact of diagnostic whole-body scan (WBS) in patients with differentiated thyroid cancer (DTC) treated with surgery and radioactive iodine (RAI) therapy. We retrospectively evaluated 606 DTC patients treated with surgery and RAI. Response to 131I therapy at 12 months was assessed by serum Tg measurement, neck ultrasound, and diagnostic WBS. According to American Thyroid Association (ATA) guidelines, patients were classified as having a low, intermediate or high risk of recurrence and at 12 months as having an excellent response (ER) or no-ER. Follow-up was then performed every 6–12 months with serum Tg determination and imaging procedures. With a median follow-up of 105 months (range 10–384), 42 (7%) events requiring further treatments occurred. Twenty-five patients had additional RAI therapy, 11 with structural disease in the thyroid bed, eight in both thyroid bed and neck lymph nodes, four had lung metastases and two had bone metastases. The other 17 patients had additional surgery for nodal disease followed by RAI therapy. The ATA intermediate and high risk of recurrence, post-operative and pre-RAI therapy Tg ≥ 10 ng/mL, and the absence of ER at 12 months were independent predictors of events. Diagnostic WBS at 12 months permitted the identification of only five recurrences among the 219 ER patients according to serum Tg levels and ultrasound. In DTC patients, the response to therapy at 12 months after RAI therapy could rely on serum Tg measurement and neck ultrasound, while diagnostic WBS was not routinely indicated in patients considered in ER.