bluuebunny/crossref_metadata_2025_split huggingface dataset:
Maplaria: a user friendly web-application for spatio-temporal malaria prevalence mapping
Authors: Giorgi Emanuele , Macharia Peter M. , Woodmansey Jack , Snow Robert W. , Rowlingson Barry 
Published: December 2021

Abstract
Background
Model-based geostatistical (MBG) methods have been extensively used to map malaria risk using community survey data in low-resource settings where disease registries are incomplete or non-existent. However, the wider adoption of MBG methods by national control programmes to inform health policy decisions is hindered by the lack of advanced statistical expertise and suitable computational equipment. Here, Maplaria, an interactive, user-friendly web-application that allows users to upload their own malaria prevalence data and carry out geostatistical prediction of annual malaria prevalence at any desired spatial scale, is introduced.

Methods
In the design of the Maplaria web application, two main criteria were considered: the application should be able to classify subnational divisions into the most likely endemicity levels; the web application should allow only minimal input from the user in the set-up of the geostatistical inference process. To achieve this, the process of fitting and validating the geostatistical models is carried out by statistical experts using publicly available malaria survey data from the Harvard database. The stage of geostatistical prediction is entirely user-driven and allows the user to upload malaria data, as well as vector data that define the administrative boundaries for the generation of spatially aggregated inferences.

Results
The process of data uploading and processing is split into a series of steps spread across screens through the progressive disclosure technique that prevents the user being immediately overwhelmed by the length of the form. Each of these is illustrated using a data set from the Malaria Indicator carried out in Tanzania in 2017 as an example.

Conclusions
Maplaria application provides a user-friendly solution to the problem making geostatistical methods more accessible to users that have not undertaken formal training in statistics. The application is a useful tool that can be used to foster ownership, among policy makers, of disease risk maps and promote better use of data for decision-making in low resource settings.
RETRACTED ARTICLE: Ginsenoside Rg3 alleviates septic liver injury by regulating the lncRNA TUG1/miR-200c-3p/SIRT1 axis
Authors: Wu Pan , Yu Xiao , Peng Yue , Wang Qian-Lu , Deng Long-Tian , Xing Wei 
Published: December 2021

Abstract

Background
Studies have shown that ginsenoside R3 (Rg3) plays a protective role in sepsis-induced organ injuries and mitochondrial dysfunction. Long noncoding RNA (lncRNA) taurine-upregulated gene 1 (TUG1) is regarded as a regulator in sepsis. However, the association between TUG1 and Rg3 remains elusive.

Methods
A sepsis mouse model was established by caecal ligation and puncture (CLP), and liver injury was induced by haematoxylin-eosin (H&E) staining. Lipopolysaccharide (LPS) was used to induce hepatocyte damage. The expression levels of TUG1, microRNA (miR)-200a-3p, and silencing information regulator 1 (SIRT1) were examined by quantitative real-time polymerase chain reaction (qRT–PCR) assays. Cell viability was monitored using the Cell Counting Kit-8 (CCK-8) assay. MitoSOX Red staining and CBIC2 (JC-1) dye were employed to detect mitochondrial reactive oxygen species (ROS) and mitochondrial transmembrane potential (MTP) levels, respectively. The interaction between miR-200a-3p and TUG1 or SIRT1 was confirmed via dual-luciferase reporter or RNA immunoprecipitation (RIP) assay.

Results
Rg3 upregulated TUG1 expression in liver tissues of CLP mice and LPS-induced hepatocytes. Rg3 could activate autophagy to improve mitochondrial dysfunction in LPS-treated hepatocytes, which was partially reversed by TUG1 depletion or miR-200a-3p overexpression. Importantly, TUG1 targeted miR-200a-3p to activate the SIRT1/AMP-activated protein kinase (AMPK) pathway in LPS-treated hepatocytes. Moreover, gain of TUG1 ameliorated mitochondrial dysfunction in LPS-treated hepatocytes by sequestering miR-200a-3p.

Conclusion
Our study revealed that Rg3 increased TUG1 expression and reduced miR-200a-3p expression to stimulate the SIRT1/AMPK pathway, thereby enhancing autophagy to improve sepsis-induced liver injury and mitochondrial dysfunction.
Remodeling immune microenvironment in periodontitis using resveratrol liposomes as an antibiotic-free therapeutic strategy
Authors: Shi Junyu , Zhang Yi , Zhang Xiaomeng , Chen Ruiying , Wei Jianxu , Hou Jiazhen , Wang Bing , Lai Hongchang , Huang Yongzhuo 
Published: December 2021

AbstractBackgroundPeriodontitis is a complicated inflammatory disease that damages the tooth-supporting tissues, with limited pharmacotherapy available. Macrophage-targeting therapy is promising for inflammatory diseases. Resveratrol (RSV), a nonflavonoid polyphenol, is known for its anti-inflammatory and immunomodulatory effects. However, its medical application is limited by its poor stability and water-solubility, as well as its low bioavailability.ResultA therapeutic resveratrol-loaded liposomal system (Lipo-RSV) was developed to treat periodontitis. The physical properties of Lipo-RSV and its ability to regulate macrophages were investigated. The results showed that Lipo-RSV had good biocompatibility and could re-educate the inflammatory macrophages from M1- to M2-like phenotype through activating p-STAT3 and downregulating p-STAT1. Besides, the Lipo-RSV could scavenge ROS and inhibit the NF-κB signal and inflammasomes, thereby reducing the pro-inflammatory cytokines IL-1β, IL-6, and TNF-α.ConclusionThese results revealed that Lipo-RSV could be a potential therapeutic system for the antibiotic-free treatment for periodontal diseases.Graphical Abstract
Phytonanotechnology applications in modern agriculture
Authors: Jiang Meng , Song Yue , Kanwar Mukesh Kumar , Ahammed Golam Jalal , Shao Shujun , Zhou Jie 
Published: December 2021

AbstractWith the rapidly changing global climate, the agricultural systems are confronted with more unpredictable and harsh environmental conditions than before which lead to compromised food production. Thus, to ensure safer and sustainable crop production, the use of advanced nanotechnological approaches in plants (phytonanotechnology) is of great significance. In this review, we summarize recent advances in phytonanotechnology in agricultural systems that can assist to meet ever-growing demands of food sustainability. The application of phytonanotechnology can change traditional agricultural systems, allowing the target-specific delivery of biomolecules (such as nucleotides and proteins) and cater the organized release of agrochemicals (such as pesticides and fertilizers). An amended comprehension of the communications between crops and nanoparticles (NPs) can improve the production of crops by enhancing tolerance towards environmental stresses and optimizing the utilization of nutrients. Besides, approaches like nanoliposomes, nanoemulsions, edible coatings, and other kinds of NPs offer numerous selections in the postharvest preservation of crops for minimizing food spoilage and thus establishing phtonanotechnology as a sustainable tool to architect modern agricultural practices.Graphical Abstract
A novel targeted multifunctional nanoplatform for visual chemo-hyperthermia synergy therapy on metastatic lymph nodes via lymphatic delivery
Authors: Liu Weiwei , Ye Xiaoping , He Lingyun , Cheng Juan , Luo Wenpei , Zheng Min , Hu Yaqin , Zhang Wei , Cao Yang , Ran Haitao , Yang Lu 
Published: December 2021

Abstract
Background
Distant metastasis to vital organs is the major contributor to breast cancer mortality, and regional lymph node metastasis is an important facilitator of distant metastasis and recurrence in this cancer. The early diagnosis and precise treatment of lymph node metastasis are crucial for staging and prognosis in breast cancer. Herein, we report a visualized precision medicine nanoplatform of metastatic lymph nodes for ultrasonic/photoacoustic (US/PA) dual modal imaging-guided in situ targeted hyperthermia-combined chemotherapy.

Results
Carbon nanoparticles (CNs), approved by the China Food and Drug Administration, were loaded with docetaxel and rationally combined with anti-hypoxia-inducible factor 1α antibody-modified poly (lactic-co-glycolic acid) (PLGA) nanoparticles to achieve the combination of passive targeting at the lymph nodes and intracellular targeting at HIF 1α factor. The accumulation and retention of nanoparticles in metastatic lymph nodes via lymphatic delivery were enhanced. Docetaxel could be effectively offloaded by CNs that have active carbon nanoparticles, and the PLGA membrane prevented drug leakage. The nanoparticles exhibited excellent photothermal performance with a photothermal conversion efficiency of 28.9%, killing tumor cells in metastatic lymph nodes through hyperthermia. In vitro and in vivo systematic evaluations revealed that hyperpyrexia triggered the rupture of nanoparticles caused by the phase transition of perfluorohexane, resulting in docetaxel release for achieving in situ hyperthermia-combined chemotherapy.

Conclusions
The laser-triggered highly efficient in situ chemotherapy nanosystem achieves targeted synergistic chemo-hyperthermia treatment of metastatic lymph nodes, and lymphatic delivery represents a strategy to avoid additional injury caused by drugs entering the blood circulation.

Graphical Abstract
Aloe derived nanovesicle as a functional carrier for indocyanine green encapsulation and phototherapy
Authors: Zeng Lupeng , Wang Huaying , Shi Wanhua , Chen Lingfan , Chen Tingting , Chen Guanyu , Wang Wenshen , Lan Jianming , Huang Zhihong , Zhang Jing , Chen Jinghua 
Published: December 2021

AbstractBackgroundCancer is one of the devastating diseases in the world. The development of nanocarrier provides a promising perspective for improving cancer therapeutic efficacy. However, the issues with potential toxicity, quantity production, and excessive costs limit their further applications in clinical practice.ResultsHerein, we proposed a nanocarrier obtained from aloe with stability and leak-proofness. We isolated nanovesicles from the gel and rind of aloe (gADNVs and rADNVs) with higher quality and yield by controlling the final centrifugation time within 20 min, and modulating the viscosity at 2.98 mPa S and 1.57 mPa S respectively. The gADNVs showed great structure and storage stability, antioxidant and antidetergent capacity. They could be efficiently taken up by melanoma cells, and with no toxicity in vitro or in vivo. Indocyanine green (ICG) loaded in gADNVs (ICG/gADNVs) showed great stability in both heating system and in serum, and its retention rate exceeded 90% after 30 days stored in gADNVs. ICG/gADNVs stored 30 days could still effectively damage melanoma cells and inhibit melanoma growth, outperforming free ICG and ICG liposomes. Interestingly, gADNVs showed prominent penetrability to mice skin which might be beneficial to noninvasive transdermal administration.ConclusionsOur research was designed to simplify the preparation of drug carrier, and reduce production cost, which provided an alternative for the development of economic and safe drug delivery system.Graphical Abstract
Mitochondria-targeted nanoplatforms for enhanced photodynamic therapy against hypoxia tumor
Authors: Wen Jiexin , Luo Yong , Gao Hui , Zhang Liang , Wang Xiang , Huang Ju , Shang Tingting , Zhou Di , Wang Dong , Wang Zhigang , Li Pan , Wang Zhaoxia 
Published: December 2021

Abstract
Background
Photodynamic therapy (PDT) is a promising therapeutic modality that can convert oxygen into cytotoxic reactive oxygen species (ROS) via photosensitizers to halt tumor growth. However, hypoxia and the unsatisfactory accumulation of photosensitizers in tumors severely diminish the therapeutic effect of PDT. In this study, a multistage nanoplatform is demonstrated to overcome these limitations by encapsulating photosensitizer IR780 and oxygen regulator 3-bromopyruvate (3BP) in poly (lactic-co-glycolic acid) (PLGA) nanocarriers.

Results
The as-synthesized nanoplatforms penetrated deeply into the interior region of tumors and preferentially remained in mitochondria due to the intrinsic characteristics of IR780. Meanwhile, 3BP could efficiently suppress oxygen consumption of tumor cells by inhibiting mitochondrial respiratory chain to further improve the generation of ROS. Furthermore, 3BP could abolish the excessive glycolytic capacity of tumor cells and lead to the collapse of ATP production, rendering tumor cells more susceptible to PDT. Successful tumor inhibition in animal models confirmed the therapeutic precision and efficiency. In addition, these nanoplatforms could act as fluorescence (FL) and photoacoustic (PA) imaging contrast agents, effectuating imaging-guided cancer treatment.

Conclusions
This study provides an ideal strategy for cancer therapy by concurrent oxygen consumption reduction, oxygen-augmented PDT, energy supply reduction, mitochondria-targeted/deep-penetrated nanoplatforms and PA/FL dual-modal imaging guidance/monitoring. It is expected that such strategy will provide a promising alternative to maximize the performance of PDT in preclinical/clinical cancer treatment.

Graphical Abstract
Second near-infrared photothermal-amplified immunotherapy using photoactivatable composite nanostimulators
Authors: Sun Haitao , Yu Tianzhu , Li Xin , Lei Yangyang , Li Jianke , Wang Xiuhui , Peng Peike , Ni Dalong , Wang Xiaolin , Luo Yu 
Published: December 2021

Abstract
Background
The construction of a nanoimmune controlled-release system that spatiotemporally recognizes tumor lesions and stimulates the immune system response step by step is one of the most potent cancer treatment strategies for improving the sensitivity of immunotherapy response.

Results
Here, a composite nanostimulator (CNS) was constructed for the release of second near-infrared (NIR-II) photothermal-mediated immune agents, thereby achieving spatiotemporally controllable photothermal-synergized immunotherapy. CNS nanoparticles comprise thermosensitive liposomes as an outer shell and are internally loaded with a NIR-II photothermal agent, copper sulfide (CuS), toll-like receptor-9 (TLR-9) agonist, cytosine-phospho-guanine oligodeoxynucleotides, and programmed death-ligand 1 (PD-L1) inhibitors (JQ1). Following NIR-II photoirradiation, CuS enabled the rapid elevation of localized temperature, achieving tumor ablation and induction of immunogenic cell death (ICD) as well as disruption of the lipid shell, enabling the precise release of two immune-therapeutical drugs in the tumor region. Combining ICD, TLR-9 stimulation, and inhibited expression of PD-L1 allows the subsequent enhancement of dendritic cell maturation and increases infiltration of cytotoxic T lymphocytes, facilitating regional antitumor immune responses.

Conclusion
CNS nanoparticle-mediated photothermal-synergized immunotherapy efficiently suppressed the growth of primary and distant tumors in two mouse models and prevented pulmonary metastasis. This study thus provides a novel sight into photo-controllably safe and efficient immunotherapy.

Graphical Abstract
Polydopamine nanoparticles attenuate retina ganglion cell degeneration and restore visual function after optic nerve injury
Authors: Lou Xiaotong , Hu Yuanyuan , Zhang Hong , Liu Jia , Zhao Yin 
Published: December 2021

Abstract
Background
Oxidative stress contributes to retina ganglion cells (RGCs) loss in variety of ocular diseases, including ocular trauma, ocular vein occlusion, and glaucoma. Scavenging the excessed reactive oxygen species (ROS) in retinal neurovascular unit could be beneficial to RGCs survival. In this study, a polydopamine (PDA)-based nanoplatform is developed to protect RGCs.

Results
The PDA nanoparticles efficiently eliminate multi-types of ROS, protect endothelia and neuronal cells from oxidative damage, and inhibit microglia activation in retinas. In an optic nerve crush (ONC) model, single intravitreal injection of PDA nanoparticles could significantly attenuate RGCs loss via eliminating ROS in retinas, reducing the inflammatory response and maintaining barrier function of retinal vascular endothelia. Comparative transcriptome analysis of the retina implied that PDA nanoparticles improve RGCs survival probably by altering the expression of genes involved in inflammation and ROS production. Importantly, as a versatile drug carrier, PDA nanoparticles could deliver brimonidine (a neuroprotection drug) to synergistically attenuate RGCs loss and promote axon regeneration, thus restore visual function.

Conclusions
The PDA nanoparticle-based therapeutic nanoplatform displayed excellent performance in ROS elimination, providing a promising probability for treating retinal degeneration diseases.

Graphical Abstract
The effects of statins on hyperandrogenism in women with polycystic ovary syndrome: a systematic review and meta-analysis of randomized controlled trials
Authors: Chen Jianguo , Huang Chaoran , Zhang Tongtong , Gong Wuqing , Deng Xiaofeng , Liu Hua , Liu Jinbo , Guo Yuanbiao 
Published: December 2021

AbstractSeveral clinical studies showed that statins were potential to treat polycystic ovary syndrome (PCOS). Through comprehensive search PubMed, EMBASE, the Web of Science, BIOSIS, the ClinialTrails.gov, and the Cochrane Library database up to 14 Feb 2020, we identified the randomized controlled trials about the treatment of statins on hyperandrogenism in PCOS women, and performed a systematic review and meta-analysis. The quality of the included studies was assessed by the Cochrane risk of bias tool and the Jadda score. Subgroup analysis and sensitivity analysis were conducted to analyze the pooled results. Nine trials included 682 PCOS patients were identified. Statins showed a significant potential to reduce testosterone (SMD = -0.47; 95% CI, − 0.76−− 0.18; P = 0.002) and dehydroepiandrosterone (SMD = -0.51; 95% CI, − 0.97−− 0.05; P = 0.03) levels, compared to the control treatments. The cutaneous symptoms hirsutism (SMD = -0.61; 95% CI, − 1.13−− 0.10; P = 0.02) and acne (SMD = -0.92; 95% CI, − 1.49−− 0.34; P = 0.002) were significantly improved by statins in PCOS women. Subgroup analysis showed that the two types of statins, and the different control treatments as well, presented no significantly different effect on testosterone and dehydroepiandrosterone. Sensitivity analysis confirmed the stability of the findings from the meta-analysis. In conclusion, statin treatment could significantly reduce androgen levels and improve cutaneous manifestations of hyperandrogenism of PCOS.
A catastrophic seronegative anti-phospholipid syndrome: case and literature review
Authors: Pinto Vanda , Ministro Augusto , Carreira Nuno Reis , Cardoso Ana , Gonçalves Catarina Sousa , Henriques Mickael , Rato João , Silva Emanuel , Pedro Luís Mendes 
Published: December 2021

Abstract
Background
Antiphospholipid Syndrome (APS) is a multisystemic autoimmune disease characterized by arterial and venous thrombosis and / or obstetric morbidity in the presence of at least one circulating anti-phospholipid antibody. The spectrum of vascular events varies from deep venous thrombosis to catastrophic APS, a rare form characterized by acute multiorgan thrombosis and high mortality.

Case report
We present the case of a 32-week pregnant woman arriving in the hospital emergency room with bilateral acute lower limb ischemia. In the obstetric evaluation, fetal death was declared. Computerized Tomography angiography showed pulmonary embolism of both pulmonary arteries, areas of splenic and right renal infarction and multiple arterial and venous thrombosis. The patient underwent urgent caesarean section and axillary-bifemoral bypass. No events registered. In the postoperative period, in an intensive care unit, treatment with rituximab and plasmapheresis were added to anticoagulant therapy. The laboratorial investigation was negative for thrombophilia and autoimmune diseases.

Conclusion
Catastrophic APS develops quickly, with multiorgan involvement and high mortality rate. The presented case poses a multidisciplinary challenge, with the surgical approach of extra-anatomical revascularization being less invasive and guaranteeing immediate perfusion of the lower limbs. Although the serological tests were negative for anti-phospholipid antibodies, this case hardly fits into another diagnosis. Therefore, it was treated as a catastrophic APS, having shown a favorable evolution.
Cancer-associated fibroblasts promote oral squamous cell carcinoma progression through LOX-mediated matrix stiffness
Authors: Zhang Jia-Yi , Zhu Wei-Wen , Wang Meng-Yao , Zhai Run-Dong , Wang Qiong , Shen Wei-Li , Liu Lai-Kui 
Published: December 2021

AbstractBackgroundCancer-associated fibroblasts (CAFs), the most abundant cells in the tumor microenvironment, have prominent roles in the development of solid tumors as stromal targets. However, the underlying mechanism of CAFs’ function in oral squamous cell carcinoma (OSCC) development remains unclear. Here, we investigated the role of lysyl oxidase (LOX) expression in CAFs in tumor stromal remodeling and the mechanism of its effect on OSCC progression.MethodsMultiple immunohistochemistry (IHC) staining was performed to detect the correlation of CAFs and LOX in the stroma of OSCC specimens, as well as the correlation with clinicopathological parameters and prognosis. The expression of LOX in CAFs were detected by RT-qPCR and western blot. The effects of LOX in CAFs on the biological characteristics of OSCC cell line were investigated using CCK-8, wound-healing and transwell assay. CAFs were co-cultured with type I collagen in vitro, and collagen contraction test, microstructure observation and rheometer were used to detect the effect of CAFs on remodeling collagen matrix. Then, collagen with different stiffness were established to investigate the effect of matrix stiffness on the progression of OSCC. Moreover, we used focal adhesion kinase (FAK) phosphorylation inhibitors to explored whether the increase in matrix stiffness promote the progression of OSCC through activating FAK phosphorylation pathway.ResultsLOX was colocalized with CAFs in the stroma of OSCC tissues, and its expression was significantly related to the degree of malignant differentiation and poor prognosis in OSCC. LOX was highly expressed in CAFs, and its knockdown impaired the proliferation, migration, invasion and EMT process of OSCC cells. The expression of LOX in CAFs can catalyze collagen crosslinking and increase matrix stiffness. Furthermore, CAFs-derived LOX-mediated increase in collagen stiffness induced morphological changes and promoted invasion and EMT process in OSCC cells by activating FAK phosphorylation pathway.ConclusionsOur findings suggest that CAFs highly express LOX in the stroma of OSCC and can remodel the matrix collagen microenvironment, and the increase in matrix stiffness mediated by CAFs-derived LOX promotes OSCC development through FAK phosphorylation pathway. Thus, LOX may be a potential target for the early diagnosis and therapeutic treatment of OSCC.