bluuebunny/crossref_metadata_2025_split huggingface dataset:
Volumetric T2-weighted MRI improves the diagnostic accuracy of spinal vascular malformations: comparative analysis with a conventional MR study
Authors: Kannath Santhosh Kumar , Rajendran Adhithyan , Thomas Bejoy , Rajan Jayadevan Enakshy 
Published: March 2019

BackgroundTo date, very little study of the importance of a volumetric T2-weighted MR sequence in the evaluation of spinal vascular malformations (SVMs) has been carried out.ObjectiveTo determine the utility and accuracy of a volumetric T2 MR sequence compared with conventional T2 in the diagnosis of SVMs.MethodsRetrospective analysis of all patients who underwent spinal DSA for suspected SVMs was conducted. Conventional T2 and volumetric T2 MR images were analysed for the presence of flow voids and parenchymal changes, and SVMs were characterized. The sensitivity, specificity, and overall diagnostic accuracy of these MRI diagnoses were calculated.ResultsOf 89 subjects included in the final analysis, 70 patients had angiographically proved SVMs (38 patients with spinal cord arteriovenous malformations [SCAVM—intramedullary or perimedullary] and 32 cases of spinal dural arteriovenous fistula (SDAVF)) and the remaining 19 subjects were normal. The sensitivity and specificity for identification of SVMs were 98.1% and 90% for volumetric T2 sequences, compared with 82.8% and 89.4% for conventional T2 MRI, respectively. For characterization of spinal vascular lesions, volumetric MRI showed high sensitivity, specificity, and accuracy for SDAVF (100%, 90%, 97%, respectively) compared with conventional T2 MRI (71.8%, 89%, 79%, respectively). The positive likelihood ratio was high and negative likelihood ratio was zero for volumetric MRI evaluation of SDAVF, while these ratios were comparable between the two sequences for SCAVM.ConclusionVolumetric T2 MRI is highly sensitive for the detection of SVMs, especially for SDAVF. Volumetric T2 MRI could be introduced into routine clinical practice in the screening of suspected SVMs.
Effect of extracranial lesion severity on outcome of endovascular thrombectomy in patients with anterior circulation tandem occlusion: analysis of the TITAN registry
Authors: Anadani Mohammad , Spiotta Alejandro , Alawieh Ali , Turjman Francis , Piotin Michel , Steglich-Arnholm Henrik , Holtmannspötter Markus , Taschner Christian , Eiden Sebastian , Haussen Diogo C , Nogueira Raul , Papanagiotou Panagiotis , Boutchakova Maria , Siddiqui Adnan H , Lapergue Bertrand , Dorn Franziska , Cognard Christophe , Killer-Oberpfalzer Monika , Mangiafico Salvatore , Ribo Marc , Psychogios Marios-Nikos , Labeyrie Marc-Antoine , Mazighi Mikael , Biondi Alessandra , Anxionnat René , Bracard Serge , Richard Sébastien , Gory Benjamin 
Published: March 2019

IntroductionEndovascular treatment (EVT) for tandem occlusion (TO) of the anterior circulation is complex but effective. The effect of extracranial internal carotid artery (EICA) lesion severity on the outcomes of EVT is unknown. In this study we investigated the effect of EICA lesion severity on the outcomes of tandem occlusion EVT.MethodsA multicenter retrospective TITAN (Thrombectomy In TANdem lesions) study that included 18 international endovascular capable centers was performed. Patients who received EVT for atherosclerotic TO with or without EICA lesion intervention were included. Patients were divided into two groups based on the EICA lesion severity (high-grade stenosis (≥90% North American Symptomatic Carotid Endarterectomy Trial) vs complete occlusion). Outcome measures included the 90-day clinical outcome (modified Rankin Scale score (mRS)), angiographic reperfusion (modified Thrombolysis In Cerebral Ischemia (mTICI) at the end of the procedure), procedural complications, and intracranial hemorrhage at 24 hours follow-up.ResultsA total of 305 patients were included in the study, of whom 135 had complete EICA occlusion and 170 had severe EICA stenosis. The EICA occlusion group had shorter mean onset-to-groin time (259±120 min vs 305±202 min; p=0.037), more patients with diabetes, and fewer with hyperlipidemia. With respect to the outcome, mTICI 2b–3 reperfusion was lower in the EICA occlusion group (70% vs 81%; p=0.03). The favorable outcome (90-day mRS 0–2), intracerebral hemorrhage and procedural complications were similar in both groups.ConclusionAtherosclerotic occlusion of the EICA in acute tandem strokes was associated with a lower rate of mTICI 2b–3 reperfusion but similar functional and safety outcomes when compared with high-grade EICA stenosis.
Syphilis associated with recreational drug use, depression and high-risk sexual behaviour in men who have sex with men: a case–control study in China
Authors: Wu Huichao , Xiu Cuizhen , Fu Xiaojing , Li Menglong , Wang Zhenhong , Li Xiufang , Wu Jing , Vermund Sten H , Hu Yifei 
Published: March 2019

ObjectiveWe investigated syphilis prevalence among men who have sex with men (MSM) in China, as well as potential risk factors. Our principal hypothesis was that syphilis would be associated with the use of recreational drugs such as methamphetamines.MethodsFrom April to October 2013, we used several methods to recruit MSM in Qingdao, collecting demographic/behavioural information via self-administrated questionnaires. Trained health workers collected blood for theTreponema pallidumparticle assay (TPPA) with positives confirmed by a toluidine red unheated serum test. We used an unmatched case–control study to identify factors that might predict syphilis infection using multivariable logistic regression.ResultsWe recruited 447 MSM who agreed to participate and who completed syphilis testing. Of 71 (15.9%) syphilis-positive MSM, 44 (62.0%) used drugs. Of 376 (84.1%) syphilis-negative MSM, 186 (49.5%) used drugs. We found a positive association with syphilis for any recreational drug use (crude OR (cOR) 1.7, 95 % CI 1.0 to 2.8), frequent methamphetamine use (cOR 2.4, 95% CI 1.1 to 5.3) and multiple drug use (adjusted OR (aOR) 3.4, 95% CI 1.3 to 9.2). Syphilis-positive men were more likely to have a higher physical depression score (aOR 5.2, 95% CI 1.1 to 24.4), be > 30 years old (aOR 2.7, 95% CI 1.5 to 4.8), report a prior STI (aOR 4.1, 95% CI 2.3 to 7.3) and report a sex party experience (aOR 2.2, 95% CI 1.1 to 4.4).ConclusionsRecreational drug use, depression and high-risk sexual behaviours were associated with syphilis infection among MSM in China. Only a multifaceted approach is likely be effective in control of both syphilis and HIV .
Motion integration is anisotropic during smooth pursuit eye movements
Authors: Souto David , Chudasama Jayesha , Kerzel Dirk , Johnston Alan 
Published: March 2019

Smooth pursuit eye movements (pursuit) are used to minimize the retinal motion of moving objects. During pursuit, the pattern of motion on the retina carries not only information about the object movement but also reafferent information about the eye movement itself. The latter arises from the retinal flow of the stationary world in the direction opposite to the eye movement. To extract the global direction of motion of the tracked object and stationary world, the visual system needs to integrate ambiguous local motion measurements (i.e., the aperture problem). Unlike the tracked object, the stationary world’s global motion is entirely determined by the eye movement and thus can be approximately derived from motor commands sent to the eye (i.e., from an efference copy). Because retinal motion opposite to the eye movement is dominant during pursuit, different motion integration mechanisms might be used for retinal motion in the same direction and opposite to pursuit. To investigate motion integration during pursuit, we tested direction discrimination of a brief change in global object motion. The global motion stimulus was a circular array of small static apertures within which one-dimensional gratings moved. We found increased coherence thresholds and a qualitatively different reflexive ocular tracking for global motion opposite to pursuit. Both effects suggest reduced sampling of motion opposite to pursuit, which results in an impaired ability to extract coherence in motion signals in the reafferent direction. We suggest that anisotropic motion integration is an adaptation to asymmetric retinal motion patterns experienced during pursuit eye movements. NEW & NOTEWORTHY This study provides a new understanding of how the visual system achieves coherent perception of an object’s motion while the eyes themselves are moving. The visual system integrates local motion measurements to create a coherent percept of object motion. An analysis of perceptual judgments and reflexive eye movements to a brief change in an object’s global motion confirms that the visual and oculomotor systems pick fewer samples to extract global motion opposite to the eye movement.
Stabilized Peptide HDAC Inhibitors Derived from HDAC1 Substrate H3K56 for the Treatment of Cancer Stem–Like Cells In Vivo
Authors: Wang Dongyuan , Li Wenjun , Zhao Rongtong , Chen Longjian , Liu Na , Tian Yuan , Zhao Hui , Xie Mingsheng , Lu Fei , Fang Qi , Liang Wei , Yin Feng , Li Zigang 
Published: March 2019

Abstract

FDA-approved HDAC inhibitors exhibit dose-limiting adverse effects; thus, we sought to improve the therapeutic windows for this class of drugs. In this report, we describe a new class of peptide-based HDAC inhibitors derived from the HDAC1-specific substrate H3K56 with improved nonspecific toxicity compared with traditional small-molecular inhibitors. We showed that our designed peptides exerted superior antiproliferation effects on cancer stem–like cells with minimal toxicity to normal cells compared with the small-molecular inhibitor SAHA, which showed nonspecific toxicity to normal and cancer cells. These peptide inhibitors also inactivated cellular HDAC1 and HDAC6 and disrupted the formation of the HDAC1, LSD1, and CoREST complex. In ovarian teratocarcinoma (PA-1) and testicular embryonic carcinoma (NTERA-2) cell xenograft animal models (5 mice/group, 50 mg/kg, every other day, intraperitoneal injection), these peptides inhibited tumor growth by 80% to 90% with negligible organ (heart, liver, spleen, lung, kidney, brain) lesions. These results represent the first attempt to design chemically stabilized peptide inhibitors to investigate HDAC inhibition in cancer stem–like cells. These novel peptide inhibitors have significantly enhanced therapeutic window and offer promising opportunities for cancer therapy.

Significance:
Selective antiproliferative effects of stabilized peptide HDAC inhibitors toward cancer stem–like cells provide a therapeutic alternative that avoids high nonspecific toxicity of current drugs.
A High Monocyte-to-Lymphocyte Ratio Predicts Poor Prognosis in Patients with Advanced Gallbladder Cancer Receiving Chemotherapy
Authors: Choi Young Hoon , Lee Jae Woo , Lee Sang Hyub , Choi Jin Ho , Kang Jinwoo , Lee Ban Seok , Paik Woo Hyun , Ryu Ji Kon , Kim Yong-Tae 
Published: March 2019

Abstract

Background:
Monocyte-to-lymphocyte ratio (MLR), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) have been reported to be prognostic markers in various cancers. However, the prognostic value of these inflammatory biomarkers, particularly MLR, in gallbladder cancer remains to be determined.

Methods:
From 2005 to 2016, 178 patients with histologically confirmed gallbladder adenocarcinoma who underwent palliative chemotherapy were queried in this study. The association between survival and various clinical and laboratory variables, including MLR, NLR, and PLR, was investigated. The optimal cutoff values for MLR, NLR, and PLR were determined using the maxstat package of R.

Results:
Patients with high MLR (&gt;0.24) were expected to have shorter progression-free survival [PFS; hazard ratio (HR), 2.100; 95% confidence interval (CI), 1.397–3.157; P &lt; 0.001] and overall survival (OS; HR, 2.533; 95% CI, 1.664–3.856; P &lt; 0.001) compared with patients with low MLR (≤0.24). In multivariate Cox model, CA 19-9, stage, and MLR were independent factors for PFS. MLR was also an independent predictor of OS along with PLR, age, and CA 19-9, whereas NLR was not significantly associated with OS. Time-dependent receiver operating characteristic (ROC) analysis showed that the area under the curve of MLR for predicting OS was greater than that of NLR and PLR at most time points.

Conclusions:
MLR independently predicts survival in gallbladder cancer patients undergoing chemotherapy. Future prospective studies are needed to validate its value as a prognostic biomarker.

Impact:
MLR is an inexpensive and easily available biomarker for predicting prognosis in patients with gallbladder cancer undergoing chemotherapy.
Childhood Body Mass Index Is Associated with Risk of Adult Colon Cancer in Men: An Association Modulated by Pubertal Change in Body Mass Index
Authors: Célind Jimmy , Ohlsson Claes , Bygdell Maria , Nethander Maria , Kindblom Jenny M. 
Published: March 2019

Abstract

Background:
The relative contribution of childhood and pubertal body mass index (BMI) for the risk of adult colorectal cancer is not known. The aim of this study was to evaluate the independent associations for childhood BMI and pubertal BMI change with risk of colorectal cancer in men.

Methods:
We included 37,663 men born in 1946 to 1961 who had weight and height measured at 8 (childhood) and 20 (young adult age) years of age available from the BMI Epidemiology Study. Information on colorectal cancer was retrieved from the Swedish National Patient Register (257 cases of colon cancer and 159 cases of rectal cancer).

Results:
Childhood BMI at 8 years of age [HR, 1.19 per SD increase; 95% confidence interval (CI), 1.06–1.33], but not pubertal BMI change (HR, 1.02; 95% CI, 0.90–1.15), was associated with increased risk of colon cancer. Due to a significant interaction between childhood BMI and pubertal BMI change (P &lt; 0.001), we stratified the analyses according to the median of pubertal BMI change. Childhood BMI was associated with risk of colon cancer in individuals with a pubertal BMI change above, but not below, the median (above: HR = 1.48, 95% CI, 1.26–1.74; below: HR = 0.95, 95% CI, 0.80–1.12). Neither childhood BMI nor pubertal BMI change was associated with rectal cancer.

Conclusions:
High childhood BMI was associated with increased risk of colon cancer only if it was followed by a pubertal BMI increase above the median.

Impact:
Further studies should evaluate prepubertal childhood BMI in relation to pubertal BMI change and BMI in middle age for the risk of colon cancer.
Circulating 25-Hydroxyvitamin D Concentration and Risk of Breast, Prostate, and Colorectal Cancers: The Melbourne Collaborative Cohort Study
Authors: Heath Alicia K. , Hodge Allison M. , Ebeling Peter R. , Eyles Darryl W. , Kvaskoff David , Buchanan Daniel D. , Giles Graham G. , Williamson Elizabeth J. , English Dallas R. 
Published: March 2019

Abstract

Background:
The role of vitamin D in cancer risk remains controversial, and limited data exist on associations between vitamin D and subtypes of specific cancers. We investigated associations between circulating 25-hydroxyvitamin D (25(OH)D) and risk of colorectal, breast, and prostate cancers, including subtypes.

Methods:
A case–cohort study within the Melbourne Collaborative Cohort Study included 547 colorectal, 634 breast, and 824 prostate cancers, and a sex-stratified random sample of participants (n = 2,996). Concentration of 25(OH)D in baseline-dried blood spots was measured using LC-MS/MS. Cox regression yielded adjusted HRs and 95% confidence intervals (CI) for each cancer in relation to plasma-equivalent 25(OH)D concentration. Associations by stage and BRAF/KRAS status for colorectal cancer, estrogen receptor status for breast cancer, and aggressiveness for prostate cancer were examined in competing risks models.

Results:
25(OH)D concentrations were inversely associated with risk of colorectal cancer [highest vs. lowest 25(OH)D quintile: HR, 0.71; 95% confidence interval (CI), 0.51–0.98], which was limited to women (HR, 0.52; 95% CI, 0.33–0.82). Circulating 25(OH)D was also inversely associated with BRAF V600E–positive colorectal cancer (per 25 nmol/L increment: HR, 0.71; 95% CI, 0.50–1.01). There were no inverse associations with breast cancer (HR, 0.98; 95% CI, 0.70–1.36) or prostate cancer (HR, 1.11; 95% CI, 0.82–1.48).

Conclusions:
Circulating 25(OH)D concentration was inversely associated with colorectal cancer risk for women, but not with risk of breast cancer or prostate cancer.

Impact:
Vitamin D might play a role in preventing colorectal cancer. Further studies are required to confirm whether vitamin D is associated with specific tumor subtypes.
Potent Antineoplastic Effects of Combined PI3Kα–MNK Inhibition in Medulloblastoma
Authors: Eckerdt Frank , Bell Jonathan B. , Beauchamp Elspeth M. , Clymer Jessica , Blyth Gavin T. , Kosciuczuk Ewa M. , Ma Quanhong , Chen David Z. , Horbinski Craig , Goldman Stewart , Munshi Hidayatullah G. , Hashizume Rintaro , Platanias Leonidas C. 
Published: March 2019

Abstract

Medulloblastoma is a highly malignant pediatric brain tumor associated with poor outcome. Developing treatments that target the cancer stem cell (CSC) population in medulloblastoma are important to prevent tumor relapse and induce long-lasting clinical responses. We utilized medulloblastoma neurospheres that display CSC characteristics and found activation of the PI3K/AKT pathway in sphere-forming cells. Of all class IA PI3Ks, only the PI3Kα isoform was required for sphere formation by medulloblastoma cells. Knockdown of p110α, but not p110β or p110δ, significantly disrupted cancer stem cell frequencies as determined by extreme limiting dilution analysis (ELDA), indicating an essential role for the PI3Kα catalytic isoform in medulloblastoma CSCs. Importantly, pharmacologic inhibition of the MAPK-interacting kinase (MNK) enhanced the antineoplastic effects of targeted PI3Kα inhibition in medulloblastoma. This indicates that MNK signaling promotes survival in medulloblastoma, suggesting dual PI3Kα and MNK inhibition may provide a novel approach to target and eliminate medulloblastoma CSCs. We also observed a significant reduction in tumor formation in subcutaneous and intracranial mouse xenograft models, which further suggests that this combinatorial approach may represent an efficient therapeutic strategy for medulloblastoma.

Implications:
These findings raise the possibility of a unique therapeutic approach for medulloblastoma, involving MNK targeting to sensitize medulloblastoma CSCs to PI3Kα inhibition.
Tumor Microenvironment Characterization in Gastric Cancer Identifies Prognostic and Immunotherapeutically Relevant Gene Signatures
Authors: Zeng Dongqiang , Li Meiyi , Zhou Rui , Zhang Jingwen , Sun Huiying , Shi Min , Bin Jianping , Liao Yulin , Rao Jinjun , Liao Wangjun 
Published: March 2019

AbstractTumor microenvironment (TME) cells constitute a vital element of tumor tissue. Increasing evidence has elucidated their clinicopathologic significance in predicting outcomes and therapeutic efficacy. Nonetheless, no studies have reported a systematic analysis of cellular interactions in the TME. In this study, we comprehensively estimated the TME infiltration patterns of 1,524 gastric cancer patients and systematically correlated the TME phenotypes with genomic characteristics and clinicopathologic features of gastric cancer using two proposed computational algorithms. Three TME phenotypes were defined, and the TMEscore was constructed using principal component analysis algorithms. The high TMEscore subtype was characterized by immune activation and response to virus and IFNγ. Activation of transforming growth factor β, epithelial–mesenchymal transition, and angiogenesis pathways were observed in the low TMEscore subtype, which are considered T-cell suppressive and may be responsible for significantly worse prognosis in gastric cancer [hazard ratio (HR), 0.42; 95% confidence interval (CI), 0.33–0.54; P &lt; 0.001]. Multivariate analysis revealed that the TMEscore was an independent prognostic biomarker, and its value in predicting immunotherapeutic outcomes was also confirmed (IMvigor210 cohort: HR, 0.63; 95% CI, 0.46–0.89; P = 0.008; GSE78220 cohort: HR, 0.25; 95% CI, 0.07–0.89; P = 0.021). Depicting a comprehensive landscape of the TME characteristics of gastric cancer may, therefore, help to interpret the responses of gastric tumors to immunotherapies and provide new strategies for the treatment of cancers.
Cancer Immunotherapy with T Cells Carrying Bispecific Receptors That Mimic Antibodies
Authors: Ahn Sarah , Li Jingjing , Sun Chuang , Gao Keliang , Hirabayashi Koichi , Li Hongxia , Savoldo Barbara , Liu Rihe , Dotti Gianpietro 
Published: March 2019

Abstract
Tumors are inherently heterogeneous in antigen expression, and escape from immune surveillance due to antigen loss remains one of the limitations of targeted immunotherapy. Despite the clinical use of adoptive therapy with chimeric antigen receptor (CAR)–redirected T cells in lymphoblastic leukemia, treatment failure due to epitope loss occurs. Targeting multiple tumor-associated antigens (TAAs) may thus improve the outcome of CAR-T cell therapies. CARs developed to simultaneously target multiple targets are limited by the large size of each single-chain variable fragment and compromised protein folding when several single chains are linearly assembled. Here, we describe single-domain antibody mimics that function within CAR parameters but form a very compact structure. We show that antibody mimics targeting EGFR and HER2 of the ErbB receptor tyrosine kinase family can be assembled into receptor molecules, which we call antibody mimic receptors (amR). These amR can redirect T cells to recognize two different epitopes of the same antigen or two different TAAs in vitro and in vivo.