bluuebunny/crossref_metadata_2025_split huggingface dataset:
Triglyceride-glucose index and the risk of stroke and its subtypes in the general population: an 11-year follow-up
Authors: Wang Anxin , Wang Guangyao , Liu Qian , Zuo Yingting , Chen Shuohua , Tao Boni , Tian Xue , Wang Penglian , Meng Xia , Wu Shouling , Wang Yongjun , Wang Yilong 
Published: February 2021

AbstractBackgroundTriglyceride-glucose (TyG) index was recently suggested to be a reliable surrogate marker of insulin resistance. We aim to investigate the associations between baseline and long-term TyG index with subsequent stroke and its subtypes in a community-based cohort.MethodsA total of 97,653 participants free of history of stroke in the Kailuan Study were included. TyG index was calculated as ln (fasting triglyceride [mg/dL] × fasting glucose [mg/dL]/2). Baseline TyG index was measured during 2006–2007. Updated cumulative average TyG index used all available TyG index from baseline to the outcome events of interest or the end of follow up. The outcome was the first occurrence of stroke, including ischemic stroke, intracerebral hemorrhage and subarachnoid hemorrhage. The associations of TyG index with outcomes were explored with Cox regression.ResultsDuring a median of 11.02 years of follow-up, 5122 participants developed stroke of whom 4277 were ischemic stroke, 880 intracerebral hemorrhage, and 144 subarachnoid hemorrhage. After adjusting for confounding variables, compared with participants in the lowest quartile of baseline TyG index, those in the third and fourth quartile were associated with an increased risk of stroke (adjusted hazard ratio [HR] 1.22, 95% confidence interval [CI] 1.12–1.33, and adjusted HR 1.32, 95% CI 1.21–1.44, respectively,Pfor trend < 0.001). We also found a linear association between baseline TyG index with stroke. Similar results were found for ischemic stroke. However, no significant associations were observed between baseline TyG index and risk of intracranial hemorrhage. Parallel results were observed for the associations of updated cumulative average TyG index with outcomes.ConclusionsElevated levels of both baseline and long-term updated cumulative average TyG index can independently predict stroke and ischemic stroke but not intracerebral hemorrhage in the general population during an 11-year follow-up.
CALM1 promotes progression and dampens chemosensitivity to EGFR inhibitor in esophageal squamous cell carcinoma
Authors: Liu Tao , Han Xiujuan , Zheng Shutao , Liu Qing , Tuerxun Aerziguli , Zhang Qiqi , Yang Lifei , Lu Xiaomei 
Published: February 2021

Abstract
Background
Calmodulin1 (CALM1) has been identified as one of the overexpression genes in a variety of cancers and EGFR inhibitor have been widely used in clinical treatment but it is unknown whether CALM1 and epidermal growth factor receptor (EGFR) have a synergistic effect in esophageal squamous cell carcinoma (ESCC). The aim of the present study was to explore the synergistic effects of knock-out CALM1 combined with EGFR inhibitor (Afatinib) and to elucidate the role of CALM1 in sensitizing the resistance to Afatinib in ESCC.

Method
Immunohistochemistry (IHC) and qRT-PCR were used to examine the expression of CALM1 and EGFR in ESCC tissues. Kaplan–Meier survival analysis was used to analyze the clinical and prognostic significance of CALM1 and EGFR expression in ESCC. Furthermore, to evaluate the biological function of CALM1 in ESCC, the latest gene editing technique CRISPR/Cas9(Clustered regularly interspaced short palindromic repeats)was applied to knockout CALM1 in ESCC cell lines KYSE150, Eca109 and TE-1. MTT, flow cytometry, Transwell migration, scratch wound-healing and colony formation assays were performed to assay the combined effect of knock-out CALM1 and EGFR inhibitor on ESCC cell proliferation and migration. In addition, nude mice xenograft model was used to observe the synergistic inhibition of knock-out CALM1 and Afatinib.

Results
Both CALM1 and EGFR were found to be significantly over-expressed in ESCC compared with paired normal control. Over-expressed CALM1 and EGFR were significantly associated with clinical stage, T classification and poor overall prognosis, respectively. In vitro, the combined effect of knock-out CALM1 mediated by the lentivirus and EGFR inhibitor was shown to be capable of inhibiting the proliferation, inducing cell cycle arrest at G1/S stage and increasing apoptosis of KYSE-150 and Eca109 cells; invasion and migration were also suppressed. In vivo, the results of tumor weight and total fluorescence were markedly reduced compared with the sgCtrl-infected group and sgCAML1 group.

Conclusion
Our data demonstrated that knock-out of CALM1 could sensitize ESCC cells to EGFR inhibitor, and it may exert oncogenic role via promotion of EMT. Taken together, CALM1 may be a tempting target to overcome Afatinib resistance.
Curcumin anti‐tumor effects on endometrial cancer with focus on its molecular targets
Authors: Jahanbakhshi Fahime , Maleki Dana Parisa , Badehnoosh Bita , Yousefi Bahman , Mansournia Mohammad Ali , Jahanshahi Moghadeseh , Asemi Zatollah , Halajzadeh Jamal 
Published: February 2021

AbstractCurcumin is extracted from turmeric and shows a variety of properties that make it a useful agent for treating diseases and targeting different biological mechanisms, including apoptosis, angiogenesis, inflammation, and oxidative stress. This phenolic compound is safe even at high doses. However, it has poor bioavailability. The incidence rates of endometrial cancer (EC) that is one of the most prevalent gynecological malignancies is increasing. Meanwhile, the onset age of EC has been decreased in past few years. Besides, EC does not show a convenient prognosis, particularly at advanced stages. Based on this information, discovering new approaches or enhancing the available ones is required to provide better care for EC patients. In this review, we cover studies concerned with the anti-tumor effects of curcumin on EC. We focus on molecular mechanisms that are targeted by curcumin treatment in different processes of cancer development and progression, such as apoptosis, inflammation, and migration. Furthermore, we present the role of curcumin in targeting some microRNAs (miRNAs) that may play a role in EC.
A model for malaria elimination based on learnings from the Malaria Elimination Demonstration Project, Mandla district, Madhya Pradesh
Authors: Rajvanshi Harsh , Bharti Praveen K. , Nisar Sekh , Jayswar Himanshu , Mishra Ashok K. , Sharma Ravendra K. , Saha Kalyan B. , Shukla Man Mohan , Wattal Suman L. , Das Aparup , Kaur Harpreet , Anvikar Anupkumar R. , Khan Azadar , Kshirsagar Nilima , Dash Aditya P. , Lal Altaf A. 
Published: February 2021

Abstract
Background
Malaria Elimination Demonstration Project (MEDP) was started as a Public-Private-Partnership between the Indian Council of Medical Research through National Institute of Research in Tribal Health, Govt. of Madhya Pradesh and Foundation of Disease Elimination and Control of India, which is a Corporate Social Responsibility (CSR) initiative of the Sun Pharmaceutical Industries Limited. The project’s goal was to demonstrate that malaria can be eliminated from a high malaria endemic district along with prevention of re-establishment of malaria and to develop a model for malaria elimination using the lessons learned and knowledge acquired from the demonstration project.

Methods
The project employed tested protocols of robust surveillance, case management, vector control, and capacity building through continuous evaluation and training. The model was developed using the learnings from the operational plan, surveillance and case management, monitoring and feedback, entomological investigations and vector control, IEC and capacity building, supply chain management, mobile application (SOCH), and independent reviews of MEDP.

Results
The MEDP has been operational since April 2017 with field operations from August 2017, and has observed: (1) reduction in indigenous cases of malaria by about 91 %; (2) need for training and capacity building of field staff for diagnosis and treatment of malaria; (3) need for improvement insecticide spraying and for distribution and usage of bed-nets; (4) need for robust surveillance system that captures and documents information on febrile cases, RDT positive individuals, and treatments provided; (5) need for effective supervision of field staff based on advance tour plan; (6) accountability and controls from the highest level to field workers; and (7) need for context-specific IEC.

Conclusions
Malaria elimination is a high-priority public health goal of the Indian Government with a committed deadline of 2030. In order to achieve this goal, built-in systems of accountability, ownership, effective management, operational, technical, and financial controls will be crucial components for malaria elimination in India. This manuscript presents a model for malaria elimination with district as an operational unit, which may be considered for malaria elimination in India and other countries with similar geography, topography, climate, endemicity, health infrastructure, and socio-economic characteristics.
Diversity-oriented synthesis derived indole based spiro and fused small molecules kills artemisinin-resistant Plasmodium falciparum
Authors: Nayak Akshaykumar , Saxena Himani , Bathula Chandramohan , Kumar Tarkeshwar , Bhattacharjee Souvik , Sen Subhabrata , Gupta Ashish 
Published: February 2021

Abstract
Background
Despite numerous efforts to eradicate the disease, malaria continues to remain one of the most dangerous infectious diseases plaguing the world. In the absence of any effective vaccines and with emerging drug resistance in the parasite against the majority of anti-malarial drugs, the search for new drugs is urgently needed for effective malaria treatment.

Methods
The goal of the present study was to examine the compound library, based on indoles generated through diversity-oriented synthesis belonging to four different architecture, i.e., 1-aryltetrahydro/dihydro-β-carbolines and piperidine/pyrrolidine-fused indole derivatives, for their in vitro anti-plasmodial activity. Trifluoroacetic acid catalyzed transformation involving tryptamine and various aldehydes/ketones provided the library.

Results
Among all the compounds screened, 1-aryltetrahydro-β-carbolines 2 and 3 displayed significant anti-plasmodial activity against both the artemisinin-sensitive and artemisinin-resistant strain of Plasmodium falciparum. It was observed that these compounds inhibited the overall parasite growth in intra-erythrocytic developmental cycle (IDC) via reactive oxygen species-mediated parasitic death and thus could be potential anti-malarial compounds.

Conclusion
Overall the compounds 2 and 3 identified in this study shows promising anti-plasmodial activity that can kill both artemisinin-sensitive and artemisinin-resistant strains of P. falciparum.
Metabolic profiling reveals interleukin-17A monoclonal antibody treatment ameliorate lipids metabolism with the potentiality to reduce cardiovascular risk in psoriasis patients
Authors: Cao Han , Su Shengmin , Yang Qi , Le Yunchen , Chen Lihong , Hu Mengyan , Guo Xiaoyu , Zheng Jie , Li Xia , Yu Yunqiu 
Published: February 2021

Abstract
Background
Psoriasis is a common chronic inflammatory skin disease associated with overproduction of interleukin-17A (IL-17A). IL-17A monoclonal antibodies (mAbs) have shown clinical efficacy in psoriasis patients. Although a series of different overlapping mechanisms have been found to establish a link between psoriasis and cardiovascular diseases, the underlying mechanisms of the two types of diseases and the potential efficacy of IL-17A mAbs in amelioration of cardiovascular comorbidities remain unclear.

Methods
Serum samples from two study cohorts including 117 individuals were analyzed using a high-throughput UHPLC-MS platform. Non-targeted metabolic profiling analysis was first conducted with samples from 28 healthy individuals and from 28 psoriasis patients before and after 12-weeks of ixekizumab treatment in study cohort 1. Study cohort 2 was additionally recruited to validate the correlations of the identified metabolites with cardiovascular diseases.

Results
A total of 43 differential metabolites, including lysophospholipids, free fatty acids, acylcarnitines and dicarboxylic acids, were accurately identified in study cohort 1, and the analysis showed that lipid metabolism was impaired in psoriasis patients. Compared with healthy individuals, psoriasis patients had higher levels of lysophosphatidylcholines, lysophosphatidylinositols, lysophosphatidic acids and free fatty acids, but lower levels of acylcarnitines and dicarboxylic acids. The identified dicarboxylic acid levels were inversely correlated with psoriasis area and severity index (PASI) scores (P < 0.05). The results for study cohort 2 were largely consistent with the results for study cohort 1. Moreover, the levels of all identified lysophosphatidylcholines were higher in psoriasis patients with coronary heart diseases than in psoriasis without coronary heart disease. Notably, most of these lipidic changes were ameliorated by ixekizumab treatment.

Conclusion
The results of this non-targeted metabolomic analysis indicate that treatment with IL-17A mAbs can not only ameliorate psoriasis lesions but also restore dysregulated lipid metabolism to normal levels in psoriasis patients. Considering that dysregulated lipid metabolism has been regarded as the critical factor in cardiovascular diseases, the recovery of lipid metabolites in psoriasis patients indicates that IL-17A mAbs might have the potential protective effects against cardiovascular comorbidities.
Sequential vs concurrent adjuvant chemotherapy of anthracycline and taxane for operable breast cancer
Authors: Chen Wanjing , Tu Qian , Shen Yanfei , Tang Kejun , Hong Mengying , Shen Yong 
Published: February 2021

Abstract
Background
Whether a sequential or concurrent regimen of anthracyclines and taxanes is superior for breast cancer is controversial. We compared the efficacy of two regimens in patients with operable breast cancer based on all relevant published data of phase III randomized controlled trials.

Methods
A comprehensive literature search on PubMed, Web of Science, Embase, ScienceDirect, Google Scholar, and ClinicalTrials.gov databases was performed up to May 2020. Meta-analysis was performed to evaluate the different efficacy on disease-free survival (DFS) and overall survival (OS) for the two chemotherapy regimens. Subgroup analyses were further carried out in terms of node status and anthracycline selection.

Results
Compared to the concurrent regimen, the sequential regimen did not improve the DFS or OS in the population studied. Subgroup analysis showed that in node-positive patients, the sequential regimen had better DFS, but not OS, than the concurrent regimen. In sequential regimen, patients who received doxorubicin and taxanes had improved DFS and OS than patients who were administered epirubicin and taxanes. Furthermore, for patients who received doxorubicin and taxanes, compared to the sequential regimen, fewer cycles (4 cycles) of concurrent treatment resulted in a worse DFS and OS, which can be rescued by more cycles (6 cycles).

Conclusions
The sequential regimen of anthracyclines and taxanes for patients with operable breast cancer did not yield a significant benefit in DFS or OS over the concurrent regimen. The sequential regimen, however, provided a better DFS than concurrent regimen for node-positive patients. Interestingly, further subgroup analysis showed that for node-positive patients who were given doxorubicin and taxanes, more cycles (6 cycles) of the concurrent regimen may rescue the efficacy for fewer cycles (4 cycles).
Does the Endoscopic Surgical Skill Qualification System improve patients’ outcome following laparoscopic surgery for colon cancer? A multicentre, retrospective analysis with propensity score matching
Authors: Kazama Keisuke , Numata Masakatsu , Aoyama Toru , Atsumi Yosuke , Tamagawa Hiroshi , Godai Teni , Saeki Hiroyuki , Saigusa Yusuke , Shiozawa Manabu , Yukawa Norio , Masuda Munetaka , Rino Yasushi 
Published: February 2021

Abstract
Background
This study aimed to investigate the short-term and oncological impact of the Endoscopic Surgical Skill Qualification System (ESSQS) by the Japan Society for Endoscopic Surgery on the operator performing laparoscopic surgery for colon cancer.

Methods
This retrospective cohort study was based on medical records from a multicentre database. A total of 417 patients diagnosed with stage II/III colon and rectosigmoid cancer treated with curative resection were divided into two groups according to whether they were operated on by qualified surgeons (Q group, n=352) or not (NQ group, n=65). Through strict propensity score matching, 98 cases (49 in each group) were assessed.

Results
Operative time was significantly longer in the NQ group than in the Q group (199 vs. 168 min, p=0.029). The amount of blood loss, post-operative complications, and duration of hospitalisation were similar between both groups. No mortality was observed. One conversion case was seen in the NQ group. The 3-year recurrence-free survival rate was 86.6% in the NQ group and 88.2% in the Q group, which was not statistically significant (log-rank p=0.966).

Conclusion
Direct operation by ESSQS-qualified surgeons contributed to a shortened operation time. Under an organised educational environment, almost equivalent safety and oncological outcomes are expected regardless of the surgeon’s qualifications.
Tumor immunogenomic signatures improve a prognostic model of melanoma survival
Authors: Morales Leah , Simpson Danny , Ferguson Robert , Cadley John , Esteva Eduardo , Monson Kelsey , Chat Vylyny , Martinez Carlos , Weber Jeffrey , Osman Iman , Kirchhoff Tomas 
Published: February 2021

Abstract
Background
Tumor mutation burden (TMB) has been associated with melanoma immunotherapy (IT) outcomes, including survival. We explored whether combining TMB with immunogenomic signatures recently identified by The Cancer Genome Atlas (TCGA) can refine melanoma prognostic models of overall survival (OS) in patients not treated by IT.

Methods
Cox proportional-hazards (Cox PH) analysis was performed on 278 metastatic melanomas from TCGA not treated by IT. In a discovery and two validation cohorts Cox PH models assessed the interaction between TMB and 53 melanoma immunogenomic features to refine prediction of melanoma OS.

Results
Interferon-γ response (IFNγRes) and macrophage regulation gene signatures (MacReg) combined with TMB significantly associated with OS (p = 8.80E−14). We observed that patients with high TMB, high IFNγRes and high MacReg had significantly better OS compared to high TMB, low IFNγRes and low MacReg (HR = 2.8, p = 3.55E−08). This association was not observed in low TMB patients.

Conclusions
We report a model combining TMB and tumor immune features that significantly improves prediction of melanoma OS, independent of IT. Our analysis revealed that patients with high TMB, high levels of IFNγRes and MacReg had significantly more favorable OS compared to high TMB patients with low IFNγRes and low MacReg. These findings may substantially improve current melanoma prognostic models.
Chimeric antigen receptor T cells engineered to secrete CD40 agonist antibodies enhance antitumor efficacy
Authors: Zhang Yajun , Wang Pei , Wang Tengjiao , Fang Yuan , Ding Yongmei , Qian Qijun 
Published: February 2021

Abstract
Background
Although chimeric antigen receptor (CAR)-T cell therapy has been remarkably successful for haematological malignancies, its efficacy against solid tumors is limited. The combination of CAR-T cell therapy with immune checkpoint inhibitors (CPIs), such as PD-1, PD-L1, and CTLA-4 antibodies, is a promising strategy for enhancing the antitumor efficacy of CAR-T cells. However, because most patients acquire resistance to CPIs, investigating other strategies is necessary to further improve the antitumor efficacy of CAR-T cell therapy for solid tumors. Recently, CD40 agonist antibodies showed potential antitumor efficacy by activating the CD40 pathway.

Results
Based on the piggyBac transposon system, rather than the widely used viral vectors, we constructed a meso3-CD40 CAR-T targeting region III of mesothelin (MSLN) that possessed the ability to secrete anti-CD40 antibodies. Compared with meso3 CAR-T cells, which did not secrete the anti-CD40 antibody, meso3-CD40 CAR-T cells secreted more cytokines and had a relatively higher proportion of central memory T (TCM) cells after stimulation by the target antigen. In addition, compared with meso3 CAR-T cells, meso3-CD40 CAR-T cells had a more powerful cytotoxic effect on target cells at a relatively low effector-to-target ratio. More importantly, we demonstrated that the antitumor activity of meso3-CD40 CAR-T cells was enhanced in a human ovarian cancer xenograft model in vivo.

Conclusions
In conclusion, these results highlight anti-CD40-secreting CAR-T cells generated by nonviral vectors as a potential clinical strategy for improving the efficacy of CAR-T cell therapies.
Platelets and lymphocytes drive progressive penumbral tissue loss during middle cerebral artery occlusion in mice
Authors: Schuhmann Michael K. , Bieber Michael , Franke Maximilian , Kollikowski Alexander M. , Stegner David , Heinze Katrin G. , Nieswandt Bernhard , Pham Mirko , Stoll Guido 
Published: February 2021

Abstract
Background
In acute ischemic stroke, cessation of blood flow causes immediate tissue necrosis within the center of the ischemic brain region accompanied by functional failure in the surrounding brain tissue designated the penumbra. The penumbra can be salvaged by timely thrombolysis/thrombectomy, the only available acute stroke treatment to date, but is progressively destroyed by the expansion of infarction. The underlying mechanisms of progressive infarction are not fully understood.

Methods
To address mechanisms, mice underwent filament occlusion of the middle cerebral artery (MCAO) for up to 4 h. Infarct development was compared between mice treated with antigen-binding fragments (Fab) against the platelet surface molecules GPIb (p0p/B Fab) or rat immunoglobulin G (IgG) Fab as control treatment. Moreover, Rag1−/− mice lacking T-cells underwent the same procedures. Infarct volumes as well as the local inflammatory response were determined during vessel occlusion.

Results
We show that blocking of the platelet adhesion receptor, glycoprotein (GP) Ibα in mice, delays cerebral infarct progression already during occlusion and thus before recanalization/reperfusion. This therapeutic effect was accompanied by decreased T-cell infiltration, particularly at the infarct border zone, which during occlusion is supplied by collateral blood flow. Accordingly, mice lacking T-cells were likewise protected from infarct progression under occlusion.

Conclusions
Progressive brain infarction can be delayed by blocking detrimental lymphocyte/platelet responses already during occlusion paving the way for ultra-early treatment strategies in hyper-acute stroke before recanalization.