bluuebunny/crossref_metadata_2025_split huggingface dataset:
Natural killer cells in cancer biology and therapy
Authors: Wu Song-Yang , Fu Tong , Jiang Yi-Zhou , Shao Zhi-Ming 
Published: August 2020

AbstractThe tumor microenvironment is highly complex, and immune escape is currently considered an important hallmark of cancer, largely contributing to tumor progression and metastasis. Named for their capability of killing target cells autonomously, natural killer (NK) cells serve as the main effector cells toward cancer in innate immunity and are highly heterogeneous in the microenvironment. Most current treatment options harnessing the tumor microenvironment focus on T cell-immunity, either by promoting activating signals or suppressing inhibitory ones. The limited success achieved by T cell immunotherapy highlights the importance of developing new-generation immunotherapeutics, for example utilizing previously ignored NK cells. Although tumors also evolve to resist NK cell-induced cytotoxicity, cytokine supplement, blockade of suppressive molecules and genetic engineering of NK cells may overcome such resistance with great promise in both solid and hematological malignancies. In this review, we summarized the fundamental characteristics and recent advances of NK cells within tumor immunometabolic microenvironment, and discussed potential application and limitations of emerging NK cell-based therapeutic strategies in the era of presicion medicine.
Clinical characterization, genetic profiling, and immune infiltration of TOX in diffuse gliomas
Authors: Zhang Hao , Fan Fan , Yu Yuanqiang , Wang Zeyu , Liu Fangkun , Dai Ziyu , Zhang Liyang , Liu Zhixiong , Cheng Quan 
Published: August 2020

AbstractBackgroundImmunotherapies targeting glioblastoma (GBM) have led to significant improvements in patient outcomes. TOX is closely associated with the immune environment surrounding tumors, but its role in gliomas is not fully understood.MethodsUsing data from The Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA), we analyzed the transcriptomes of 1691 WHO grade I-IV human glioma samples. The R language was used to perform most of the statistical analyses. Somatic mutations and somatic copy number variation (CNV) were analyzed using GISTIC 2.0.ResultsTOX was down-regulated in malignant gliomas compared to low grade gliomas, and upregulated in the proneural and IDH mutant subtypes of GBM. TOXlowtumours are associated with the loss of PTEN and amplification of EGFR, while TOXhightumours harbor frequent mutations in IDH1 (91%). TOX was highly expressed in leading edge regions of tumours. Gene ontology and pathway analyses demonstrated that TOX was enriched in multiple immune related processes including lymphocyte migration in GBM. Finally, TOX had a negative association with the infiltration of several immune cell types in the tumour microenvironment.ConclusionTOX has the potential to be a new prognostic marker for GBM.
Wheat ear counting using K-means clustering segmentation and convolutional neural network
Authors: Xu Xin , Li Haiyang , Yin Fei , Xi Lei , Qiao Hongbo , Ma Zhaowu , Shen Shuaijie , Jiang Binchao , Ma Xinming 
Published: August 2020

Abstract
Background
Wheat yield is influenced by the number of ears per unit area, and manual counting has traditionally been used to estimate wheat yield. To realize rapid and accurate wheat ear counting, K-means clustering was used for the automatic segmentation of wheat ear images captured by hand-held devices. The segmented data set was constructed by creating four categories of image labels: non-wheat ear, one wheat ear, two wheat ears, and three wheat ears, which was then was sent into the convolution neural network (CNN) model for training and testing to reduce the complexity of the model.

Results
The recognition accuracy of non-wheat, one wheat, two wheat ears, and three wheat ears were 99.8, 97.5, 98.07, and 98.5%, respectively. The model R2 reached 0.96, the root mean square error (RMSE) was 10.84 ears, the macro F1-score and micro F1-score both achieved 98.47%, and the best performance was observed during late grain-filling stage (R2 = 0.99, RMSE = 3.24 ears). The model could also be applied to the UAV platform (R2 = 0.97, RMSE = 9.47 ears).

Conclusions
The classification of segmented images as opposed to target recognition not only reduces the workload of manual annotation but also improves significantly the efficiency and accuracy of wheat ear counting, thus meeting the requirements of wheat yield estimation in the field environment.
A succinct technique for the extraction of the proximal femoral nail anti-rotation (PFNA) after unlocking failure: a case report
Authors: Cao Ming-de , Yang Zhong-Meng , Lu Hua-Ding 
Published: August 2020

Abstract
Introduction
Proximal femoral nail anti-rotation (PFNA) is a routine method to deal with intertrochanteric fractures in the elder population. It is challenging to remove PFNA in some cases as a result of stripping of blade heads. In this case presentation, we describe a novel technique using commonly available instruments that can be used to remove stripped, even broken anti-rotation blade where conventional methods have failed.

Methods
The subject underwent a PFNA removal surgery 15 months after the previous fixation. We encountered difficulties using the regular instrument to remove the anti-rotation blade. A 5-mm tungsten carbide bur was used to drill a single cortical hole at the end of the blade. Then double-strand steel wire was threaded through the hole, and the distal part was shaped into a circle which could tie to the extraction screw. Slide Hammer was applied to gently knock out the blade along the anatomical direction of the femoral neck.

Results
The technique helped us successfully remove the anti-rotation blade and provided the patient with a satisfactory result.

Conclusion
The use of a tungsten reamer and steel wire loop to remove the proximal femoral anti-rotation blade may provide a cost-effective and straightforward method of dealing with extraction failure.
Atorvastatin promotes bone formation in aged apoE–/– mice through the Sirt1–Runx2 axis
Authors: Hong Wei , Wei Zhanying , Qiu Zhaohui , Li Zheng , Fu Chensheng , Ye Zhibin , Xu Xiaoya 
Published: August 2020

AbstractBackgroundStatins are the most widely used drugs in elderly patients; the most common clinical application of statins is in aged hyperlipemia patients. There are few studies on the effects and mechanisms of statins on bone in elderly mice with hyperlipemia. The study is to examine the effects of atorvastatin on bone phenotypes and metabolism in aged apolipoprotein E-deficient (apoE–/–) mice, and the possible mechanisms involved in these changes.MethodsTwenty-four 60-week-old apoE–/–mice were randomly allocated to two groups. Twelve mice were orally gavaged with atorvastatin (10 mg/kg body weight/day) for 12 weeks; the others served as the control group. Bone mass and skeletal microarchitecture were determined using micro-CT. Bone metabolism was assessed by serum analyses, qRT-PCR, and Western blot. Bone marrow-derived mesenchymal stem cells (BMSCs) from apoE–/–mice were differentiated into osteoblasts and treated with atorvastatin and silent information regulator 1 (Sirt1) inhibitor EX-527.ResultsThe results showed that long-term administration of atorvastatin increases bone mass and improves bone microarchitecture in trabecular bone but not in cortical bone. Furthermore, the serum bone formation marker osteocalcin (OCN) was ameliorated by atorvastatin, whereas the bone resorption marker tartrate-resistant acid phosphatase 5b (Trap5b) did not appear obviously changes after the treatment of atorvastatin. The mRNA expression of Sirt1, runt-related transcription factor 2 (Runx2), alkaline phosphatase (ALP), and OCN in bone tissue were increased after atorvastatin administration. Western blot showed same trend in Sirt1 and Runx2. The in vitro study showed that when BMSCs from apoE–/–mice were pretreated with EX527, the higher expression of Runx2, ALP, and OCN activated by atorvastatin decreased significantly or showed no difference compared with the control. The protein expression of Runx2 showed same trend.ConclusionsAccordingly, the current study validates the hypothesis that atorvastatin can increase bone mass and promote osteogenesis in aged apoE−/−mice by regulating the Sirt1–Runx2 axis.
Functional deficits in chronic mechanical ankle instability
Authors: Wenning Markus , Gehring Dominic , Mauch Marlene , Schmal Hagen , Ritzmann Ramona , Paul Jochen 
Published: August 2020

Abstract
Background
The interaction of functional and mechanical deficits in chronic ankle instability remains a major issue in current research. After an index sprain, some patients develop sufficient coping strategies, while others require mechanical support. This study aimed to analyze persisting functional deficits in mechanically unstable ankles requiring operative stabilization.

Methods
We retrospectively analyzed the functional testing of 43 patients suffering from chronic, unilateral mechanical ankle instability (MAI) and in which long-term conservative treatment had failed. Manual testing and arthroscopy confirmed mechanical instability. The functional testing included balance test, gait analysis, and concentric-concentric, isokinetic strength measurements and was compared between the non-affected and the MAI ankles.

Results
Plantarflexion, supination, and pronation strength was significantly reduced in MAI ankles. A sub-analysis of the strength measurement revealed that in non-MAI ankles, the peak pronation torque was reached earlier during pronation (maximum peak torque angle at 20° vs. 14° of supination, p < 0.001). Furthermore, active range of motion was reduced in dorsiflexion and supination. In balance testing, patients exhibited a significant increased perimeter for the injured ankle (p < 0.02). During gait analysis, we observed an increased external rotation in MAI (8.7 vs. 6.8°, p<0.02).

Conclusions
This study assesses functional deficits existent in a well-defined population of patients suffering from chronic MAI. Impairments of postural sway, gait asymmetries, and asymmetric isokinetic strength can be observed despite long-term functional treatment. The finding that pronation strength is particularly reduced with the foot in a close-to-accident position indicates potential muscular dysfunction in MAI. Possibly, these deficits alongside the underlying mechanical instability characterize patients requiring mechanical stabilization.
Timing of norepinephrine initiation in patients with septic shock: a systematic review and meta-analysis
Authors: Li Yuting , Li Hongxiang , Zhang Dong 
Published: August 2020

Abstract
Background
The effect of the timing of norepinephrine initiation on clinical outcomes in patients with septic shock is uncertain. A systematic review and meta-analysis was performed to evaluate the impact of early and late start of norepinephrine support on clinical outcomes in patients with septic shock.

Methods
We searched the PubMed, Cochrane, and Embase databases for randomized controlled trials (RCTs) and cohort studies from inception to the 1st of March 2020. We included studies involving adult patients (> 18 years) with septic shock. All authors reported our primary outcome of short-term mortality and clearly comparing early versus late norepinephrine initiation with clinically relevant secondary outcomes (ICU length of stay, time to achieved target mean arterial pressure (≥ 65 mmHg), and volume of intravenous fluids within 6 h). Results were expressed as odds ratio (OR) and mean difference (MD) with accompanying 95% confidence interval (CI).

Results
Five studies including 929 patients were included. The primary outcome of this meta-analysis showed that the short-term mortality of the early group was lower than that of the late group (odds ratio [OR] = 0.45; 95% CI, 0.34 to 0.61; P < 0.00001; χ2 = 3.74; I2 = 0%). Secondary outcomes demonstrated that the time to achieved target MAP of the early group was shorter than that of the late group (mean difference = − 1.39; 95% CI, − 1.81 to − 0.96; P < 0.00001; χ2 = 1.03; I2 = 0%). The volume of intravenous fluids within 6 h of the early group was less than that of the late group (mean difference = − 0.50; 95% CI, − 0.68 to − 0.32; P < 0.00001; χ2 = 33.76; I2 = 94%). There was no statistically significant difference in the ICU length of stay between the two groups (mean difference = − 0.11; 95% CI, − 1.27 to 1.05; P = 0.86; χ2 = 0.85; I2 = 0%).

Conclusions
Early initiation of norepinephrine in patients with septic shock was associated with decreased short-term mortality, shorter time to achieved target MAP, and less volume of intravenous fluids within 6 h. There was no significant difference in ICU length of stay between early and late groups. Further large-scale RCTs are still required to confirm these results.
Epigenetic age and pregnancy outcomes: GrimAge acceleration is associated with shorter gestational length and lower birthweight
Authors: Ross Kharah M. , Carroll Judith E. , Horvath Steve , Hobel Calvin J. , Coussons-Read Mary E. , Dunkel Schetter Christine 
Published: August 2020

Abstract
Background
Advanced biological aging, as measured by epigenetic aging indices, is associated with early mortality and morbidity. Associations between maternal epigenetic aging indices in pregnancy and pregnancy outcomes, namely gestational length and birthweight, have not been assessed. The purpose of this study was to examine whether epigenetic age during pregnancy was associated with gestational length and birthweight.

Results
The sample consisted of 77 women from the Los Angeles, CA, area enrolled in the Healthy Babies Before Birth study. Whole blood samples for DNA methylation assay were obtained during the second trimester (15.6 ± 2.15 weeks gestation). Epigenetic age indices GrimAge acceleration (GrimAgeAccel), DNAm PAI-1, DNAm ADM, and DNAm cystatin C were calculated. Gestational length and birthweight were obtained from medical chart review. Covariates were maternal sociodemographic variables, gestational age at blood sample collection, and pre-pregnancy body mass index. In separate covariate-adjusted linear regression models, higher early second trimester GrimAgeAccel, b(SE) = − .171 (.056), p = .004; DNAm PAI-1, b(SE) = − 1.95 × 10−4 (8.5 × 10−5), p = .004; DNAm ADM, b(SE) = − .033 (.011), p = .003; and DNAm cystatin C, b(SE) = 2.10 × 10−5 (8.0 × 10−5), p = .012, were each associated with shorter gestational length. Higher GrimAgeAccel, b(SE) = − 75.2 (19.7), p < .001; DNAm PAI-1, b(SE) = − .079(.031), p = .013; DNAm ADM, b(SE) = − 13.8 (3.87), p = .001; and DNAm cystatin C, b(SE) = − .010 (.003), p = .001, were also associated with lower birthweight, independent of gestational length.

Discussion
Higher maternal prenatal GrimAgeAccel, DNAm PAI-1, DNAm ADM, and DNAm cystatin C were associated with shorter gestational length and lower birthweight. These findings suggest that biological age, as measured by these epigenetic indices, could indicate risk for adverse pregnancy outcomes.
Improving detection of work-related asthma: a review of gaps in awareness, reporting and knowledge translation
Authors: MacKinnon Madison , To Teresa , Ramsey Clare , Lemière Catherine , Lougheed M. Diane 
Published: August 2020

Abstract
Background
Work-related asthma (WRA) accounts for up to 25% of all adults with asthma. Early diagnosis is key for optimal management as delays in diagnosis are associated with worse outcomes. However, WRA is significantly underreported and the median time to diagnosis is 4 years. The objective of this review is to identify the gaps in awareness and reporting of WRA and identify gaps in current knowledge translation strategies for chronic disease in general, and asthma specifically. This will identify reasons for delays in WRA diagnosis, as well inform suggestions to improve knowledge translation strategies for dissemination and implementation of WRA prevention and management guidelines.

Methods
Non-systematic literature reviews were conducted on PubMed with a focus on work-related asthma screening and diagnosis, and knowledge translation or translational medicine research in asthma and chronic disease. In total, 3571 titles and abstracts were reviewed with no restriction on date published. Of those, 207 were relevant and fully read. Another 37 articles were included and reviewed after citation reviews of articles from the initial search and from suggestions from editors. In total, 63 articles were included in the final review.

Results
Patients, employers, and healthcare professionals lack awareness and under-report WRA which contribute to the delayed diagnosis of WRA, primarily through lack of education, stigma associated with WRA, and lack of awareness and screening in primary care. Knowledge translation strategies for asthma research typically involve the creation of guidelines for diagnosis of the disease, asthma care plans and tools for education and management. While there are some prevention programs in place for certain industries, gaps in knowledge translation strategies including lack of screening tools currently available for WRA, poor education of employers and physicians in identifying WRA, and education of patients is often done post-diagnosis and focuses on management rather than prevention or screening.

Conclusion
Future knowledge translation strategies should focus on educating employees and employers well before potential exposure to agents associated with WRA and screening for WRA in primary care to enable health care providers to recognize and diagnose WRA.
Hypoxia alleviates dexamethasone-induced inhibition of angiogenesis in cocultures of HUVECs and rBMSCs via HIF-1α
Authors: Chai Miaomiao , Gu Ce , Shen Qihua , Liu Jiaxing , Zhou Yi , Jin Ziyang , Xiong Wanli , Zhou Yan , Tan Wensong 
Published: August 2020

AbstractBackground and aimInadequate vascularization is a challenge in bone tissue engineering because internal cells are prone to necrosis due to a lack of nutrient supply. Rat bone marrow-derived mesenchymal stem cells (rBMSCs) and human umbilical vein endothelial cells (HUVECs) were cocultured to construct prevascularized bone tissue in osteogenic induction medium (OIM) in vitro. The angiogenic capacity of HUVECs was limited in the coculture system. In this study, the effects of the components in the medium on HUVEC angiogenesis were analyzed.MethodsThe coculture system was established in OIM. Alizarin red staining and alkaline phosphatase staining were used to assess the osteogenic ability of MSCs. A Matrigel tube assay was used to assess the angiogenic ability of HUVECs in vitro. The proliferation of HUVECs was evaluated by cell counting and CCK-8 assays, and migration was evaluated by the streaked plate assay. The expression levels of angiogenesis-associated genes and proteins in HUVECs were measured by qRT-PCR and Western blotting, respectively.ResultsDexamethasone in the OIM suppressed the proliferation and migration of HUVECs, inhibiting the formation of capillary-like structures. Our research showed that dexamethasone stimulated HUVECs to secrete tissue inhibitor of metalloproteinase (TIMP-3), which competed with vascular endothelial growth factor (VEGF-A) to bind to vascular endothelial growth factor receptor 2 (VEGFR2, KDR). This effect was related to inhibiting the phosphorylation of ERK and AKT, which are two downstream targets of KDR. However, under hypoxia, the enhanced expression of hypoxia-inducible factor-1α (HIF-1α) decreased the expression of TIMP-3 and promoted the phosphorylation of KDR, improving HUVEC angiogenesis in the coculture system.ConclusionCoculture of hypoxia-preconditioned HUVECs and MSCs showed robust angiogenesis and osteogenesis in OIM, which has important implications for prevascularization in bone tissue engineering in the future.
Successful treatment of lipofibromatosis-like neural tumor of the lumbar spine with an NTRK-fusion inhibitor
Authors: Dupuis Megan , Shen Yulei , Curcio Christian , Meis Jeanne M. , Wang Wei-Lien , Amini Behrang , Rhines Laurence , Reuther Jacquelyn , Roy Angshumoy , Fisher Kevin E. , Conley Anthony P. , Andrew Livingston J. 
Published: August 2020

Abstract
Background
Lipofibromatosis-like neural tumors (LPF-NT) are a newly identified class of rare mesenchymal neoplasms. Current standard of care therapy is surgical resection alone; there are no chemotherapies or molecular targeted therapies that have been shown to be effective in patients who are not surgical candidates due to either tumor bulk or location. Most LPF-NT harbor NTRK fusions, although the therapeutic significance of these fusions has not been previously demonstrated in this malignancy. Here, we present the first case of a patient with surgically-unresectable LPF-NT successfully treated with medical therapy, specifically the TRK fusion-protein inhibitor entrectinib.

Case presentation
The patient is a 21 year old man with no co-morbidities who presented for evaluation due to intermittent abdominal pain and was found to have a mass spanning from T12-L2. Biopsy revealed a mesenchymal spindle cell neoplasm and S100 positivity pointed to possible nerve sheath origin. The sample was ultimately found to have an LMNA-NTRK1 fusion, confirming the diagnosis of LP-NFT. Unfortunately, due to the bulk and location of the tumor, surgery was felt to be exceptionally morbid and the patient was treated in a clinical trial with the NTRK inhibitor entrectinib. Surprisingly, he had such a robust clinical response that he was ultimately deemed a surgical candidate and he was successfully taken to surgery. Post-operative pathology revealed > 95% necrosis, demonstrating exceptional sensitivity to the targeted therapy. The patient remains NED and on entrectinib 12 months post-operatively.

Conclusions
The exceptional treatment response of this patient suggests that NTRK fusions are true drivers of the disease. Thus, all patients should be evaluated for NTRK fusions using sensitive methodologies and treatment with TRK fusion-protein inhibitors should be considered in patients who are not candidates for oncologic resection.
Protective effect of Lactobacillus plantarum ATCC8014 on acrylamide-induced oxidative damage in rats
Authors: Zhao Sijia , Zhao Xiaoduo , Liu Qingbo , Jiang Yujun , Li Yanhua , Feng Wenxiao , Xu Honghua , Shao Meili 
Published: August 2020

AbstractAcrylamide (AA), which is mainly found in fried foods, causes neurotoxicity, genetic toxicity, carcinogenic effects, and DNA damage. This study confirms that a strain of lactic acid bacteria (Lactobacillus plantarum ATCC8014) could alleviate the toxicity of rats by inhibiting the AA-induced oxidative damage. Forty-eight adult male SD rats were randomly divided into eight groups: control group, AA group (40 mg/kg), three different doses (1 × 107 CFU/ml, 1 × 108 CFU/ml, 1 × 109 CFU/ml of Lactobacillus plantarum ATCC8014) of prevention groups and therapeutic groups, respectively. At the end of three-week experiment, AA treatment produced a significant reduction in the rate of weight gain along with the symptoms of hind limb splay and ataxia. Histological examinations revealed various degrees of injury in five tissues. Levels of superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) in group AA rats were significantly decreased, but the level of lipid peroxidation (LPO) was significantly increased (p < 0.05). Both prevention and therapeutic groups with 1 × 109 CFU/ml of Lactobacillus plantarum ATCC8014 could effectively reduce the injury of AA to the body. However, reductions in both groups were not statistically significant.