bluuebunny/crossref_metadata_2025_split huggingface dataset:
Flavonoids in a crude extract of Catha edulis inhibit rat intestinal contraction via blocking Ca2+ channels
Authors: Nigusse Tadele , Zhang Ling , Wang Rong , Wang Xiao‐Ning , Li Jingxin , Liu Chuanyong 
Published: April 2019

AbstractBackgroundAnimal studies show that Catha edulis inhibits gastrointestinal tract motility. However, there is little or no information on its effect on colon motility and the mechanism of action and active constituents responsible for this effect. This study therefore attempted to discern the effect, suggest the mechanism, and identify the active compounds from the crude extract.MethodsA crude extract of Catha edulis was fractionated and subfractionated using column chromatography and HPLC. The activity of all fractions and subfractions was evaluated on rat colon longitudinal muscle. Nuclear magnetic resonance (NMR) spectroscopic data elucidations were used to identify the active compounds. An ileal segment preparation was used to investigate the possible mechanism of action.ResultsThe crude extract of Catha edulis (0.05‐0.5 mg/mL) inhibited spontaneous contraction of rat colon and ileum (P < 0.05), and tetrodotoxin (TTX, 10 µmol/L) failed to block this effect. Similar to verapamil (0.01‐0.1 μmol/L), the Catha edulis extract (0.05‐0.5 mg/mL) inhibited high K+ (80 mmol/L)‐induced sustained ileal contraction and decreased the response to Ca2+. Analysis of the NMR data showed that quercetin, kaempferol, and myricetin were the active phytochemicals. All the identified compounds were flavonoids and significantly inhibited (P < 0.05) spontaneous contraction of the rat colon longitudinal muscle compared to controls.ConclusionsThe crude extract of Catha edulis has a spasmolytic effect on the rat ileum, which is mediated through blocking Ca2+ channels, and quercetin, kaempferol, and myricetin were found to be the causative compounds.
Sirolimus‐associated pericardial effusion with cardiac tamponade and interstitial pneumonitis in a hematopoietic stem cell transplant recipient
Authors: Joo Su Jin , Yildirim Inci , Stenger Elizabeth O. , Anderson Evan J. 
Published: April 2019

AbstractSirolimus, a mammalian target of rapamycin (mTOR) inhibitor, is a potent immunosuppressant that is increasingly used in prevention and treatment of graft‐vs‐host disease (GVHD) in allogeneic hematopoietic stem cell transplant (HSCT) patients. However, data regarding its adverse effects in HSCT patients remain limited. We describe an 18‐year‐old HSCT patient with a history of invasive fungal infection, who developed pericardial effusion with cardiac tamponade and interstitial pneumonitis while receiving sirolimus for GVHD prophylaxis. Our case illustrates potentially life‐threatening complications of sirolimus use in allogeneic HSCT patients.
Target‐related parietal P3 and medial frontal theta index the genetic risk for problematic substance use
Authors: Harper Jeremy , Malone Stephen M. , Iacono William G. 
Published: April 2019

AbstractTheoretical and empirical work suggests that problematic substance use (PSU) is associated with individual differences in prefrontal cortex activity. While research has strongly linked parietal P3 amplitude reduction (P3AR) to genetic risk for problematic substance use, few studies have tested whether prefrontal EEG measures are sensitive to this genetic liability. In addition to P3, oddball target detection tasks elicit medial frontal theta power, reflecting attentional allocation, and parietal delta, indexing decision making or stimulus‐response link updating. Midfrontal theta and parietal delta may index neurocognitive processes relevant to PSU beyond P3AR. The present investigation examined the etiological relationship between PSU and P3, frontal theta, and parietal delta in a large twin sample (N = 754). EEG was recorded during a visual oddball task. Greater PSU was associated with reduced target P3 amplitude and midfrontal theta/parietal delta power, and increased mean reaction time and reaction time variability (RTV; indexing attentional fluctuations). P3, theta, and RTV, but not delta or mean RT, explained unique variance in PSU (R2 = 0.04). Twin biometric modeling indicated a genetic relationship between PSU and P3, theta, and RTV. Theta accounted for distinct genetic variance in PSU beyond P3 and RTV. Together, 23% of the total additive genetic variance in PSU was explained by the three endophenotypes. Results replicate P3AR as an endophenotype and provide support for additional behavioral (RTV) and neurophysiological (midfrontal theta) endophenotypes of PSU. Reduced theta and greater RTV may reflect variations in a prefrontal attentional network that confers genetic risk for substance use problems.
Policy Narratives across Two Languages: A Comparative Study using the Narrative Policy Framework
Authors: Huda Juhi 
Published: April 2019

AbstractThe Narrative Policy Framework (NPF) focuses on the role of narratives, drawing from a rich scholarship in narrative, language, and culture. Despite the understanding that narratives are constructions of language and that narrative construction differs across languages, NPF studies have not focused on policy narratives in languages other than English. Language characteristics of narratives are important to assess the stability of policy narratives when there are multiple dominant languages in a political system. This study investigates the use of narrative elements in policy narratives in agricultural biotechnology policy in India across Hindi and English media coverage to examine the NPF assumption that narratives have generalizable narrative elements irrespective of variation in linguistic context and, specifically, tests the transportability of narrative elements. Findings validate the transportability of narrative elements in Hindi narratives, indicate variation in the use of narrative elements over time, and have implications for applying NPF across languages.
Enabling diverse learners to thrive in the online homiletics classroom
Authors: Lamb Lisa 
Published: April 2019

AbstractMany early efforts at teaching preaching online incurred disastrous losses in quality. Revamped versions now claim to meet, and in some areas even exceed, classroom learning effectiveness, with potentially significant gains for students from non‐dominant cultures. Students preach in local ethnic and denominational contexts, so a wider range of sermon styles can flourish in indigenous soil. Students hear immediate feedback from their community, and from their online peers and professor. Online discussion formats level the playing field for non‐native speakers. By remaining embedded in their denominational and ethnic environments, student's cultural differences may be simultaneously affirmed and critiqued. This article describes capacities which predict success among preaching students, and how culture may influence the manifestation of these capacities. It details best practices and continuing challenges for professors making the transition to online preaching courses, as they seek to build culturally sustaining learning environments in which diverse students may flourish.
Analogous activities: Tools for thinking comparatively in religious studies courses
Authors: McGuire Beverley 
Published: April 2019

AbstractThis article discusses an experiential teaching method that uses secular activities that are simple, accessible, and analogous to religious practice in order to facilitate comparative religious study. These “analogous activities” – for example, social rituals, stillness, yoga, a social media fast, singing, nonviolent communication, and mindfulness meditation – provide a third point of reference that allows students to pivot between their understanding of religion and those of practitioners and scholars of religion. Experiential learning can be quite successful if deliberately sequenced to allow students to encounter a series of interpretive frameworks and structured with prompts and parameters that encourage reflection and critical analysis of their experience. In my course engaging in analogous activities not only impacted students' understanding of Asian religions, but also led them to question two previous assumptions: first, that religious beliefs were more important than religious practices, which is particularly problematic in regards to Asian religious traditions that place more emphasis on orthopraxy than orthodoxy, and second, that religion was something separate from one's everyday or lived reality.
Survival analysis in dogs with urinary transitional cell carcinoma that underwent whole‐body computed tomography at diagnosis
Authors: Iwasaki Ryota , Shimosato Yuka , Yoshikawa Ryutaro , Goto Sho , Yoshida Kyoko , Murakami Mami , Kawabe Mifumi , Sakai Hiroki , Mori Takashi 
Published: April 2019

AbstractThis retrospective study aimed to evaluate factors associated with survival and to compare characteristics between tumour localizations in dogs with urinary transitional cell carcinoma (TCC) that underwent whole‐body computed tomography (CT) at diagnosis. Dogs with histologically confirmed TCC that received medical therapy between 2010 and 2017 were included; dogs that underwent surgery or radiotherapy for the primary tumour were excluded. According to the CT findings, primary tumour localization (classified into the Bladder, Urethra and Bladder and Urethra groups), prostate involvement, iliosacral lymphadenomegaly, sternal lymphadenomegaly and metastasis to the bone and lung were evaluated for survival analysis. CT at diagnosis revealed iliosacral lymphadenomegaly, sternal lymphadenomegaly, bone metastasis and lung metastasis in 47.7%, 18.5%, 24.6% and 35.4% of the 65 included dogs, respectively. The overall median survival time was 196 days. On multivariable analysis, TCC localization (hazard ratio [HR], 1.90; P = .037), bone metastasis (HR, 2.76; P = .013) and sternal lymphadenomegaly (HR, 3.56; P = .004) were significantly associated with survival. Compared to the Bladder group (n = 16), the Urethra group (n = 26) had higher metastasis rates to the bone (6.3% vs 42.3%; P = .045) and lung (6.3% vs 46.2%; P = .022). The survival time was shorter in the Urethra group than in the Bladder group (121.5 vs 420 days; P < .001), and it was similar only in female dogs (247 vs 420 days; P = .031). These findings suggest that whole‐body CT could be valuable for predicting the prognosis in urinary TCC.
Thoracic involvement of diffuse lymphangiomatosis successfully treated with sildenafil
Authors: Maurac Arnaud , Debray Marie-Pierre , Crestani Bruno , Taillé Camille 
Published: April 2019

General lymphatic anomaly (GLA) is a very rare disorder, characterised by multifocal lymphatic malformations into various tissues that is due to congenital abnormalities of lymphatic development. No treatment has ever proved its efficiency.We report a 22-year-old man with recurrent bronchial casts due to thoracic involvement of GLA. After a 6-month treatment with sildenafil (20 mg three times a day), a phosphodiesterase 5 inhibitor, chest CT scan showed a complete regression of ground-glass opacities and lung function test results improved substantially and remained stable for 1 year. The treatment was well tolerated.This observation suggests that sildenafil may be a therapeutic approach to be tested in thoracic involvement of GLA.
Bi-allelic loss of function variants ofTBX6causes a spectrum of malformation of spine and rib including congenital scoliosis and spondylocostal dysostosis
Authors: Otomo Nao , Takeda Kazuki , Kawai Shunsuke , Kou Ikuyo , Guo Long , Osawa Mitsujiro , Alev Cantas , Kawakami Noriaki , Miyake Noriko , Matsumoto Naomichi , Yasuhiko Yukuto , Kotani Toshiaki , Suzuki Teppei , Uno Koki , Sudo Hideki , Inami Satoshi , Taneichi Hiroshi , Shigematsu Hideki , Watanabe Kei , Yonezawa Ikuho , Sugawara Ryo , Taniguchi Yuki , Minami Shohei , Kaneko Kazuo , Nakamura Masaya , Matsumoto Morio , Toguchida Junya , Watanabe Kota , Ikegawa Shiro 
Published: April 2019

BackgroundCongenital scoliosis (CS) is a common vertebral malformation. Spondylocostal dysostosis (SCD) is a rare skeletal dysplasia characterised by multiple vertebral malformations and rib anomalies. In a previous study, a compound heterozygosity for a null mutation and a risk haplotype composed by three single-nucleotide polymorphisms inTBX6have been reported as a disease-causing model of CS. Another study identified bi-allelic missense variants in a SCD patient. The purpose of our study is to identifyTBX6variants in CS and SCD and examine their pathogenicity.MethodsWe recruited 200 patients with CS or SCD and investigatedTBX6variants. We evaluated the pathogenicity of the variants by in silico prediction and in vitro experiments.ResultsWe identified five 16p11.2 deletions, one splice-site variant and five missense variants in 10 patients. In vitro functional assays for missense variants identified in the previous and present studies demonstrated that most of the variants caused abnormal localisation of TBX6 proteins. We confirmed mislocalisation of TBX6 proteins in presomitic mesoderm cells induced from SCD patient-derived iPS cells. In induced cells, we found decreased mRNA expressions ofTBX6and its downstream genes were involved in somite formation. All CS patients with missense variants had the risk haplotype in the opposite allele, while a SCD patient with bi-allelic missense variants did not have the haplotype.ConclusionsOur study suggests that bi-allelic loss of function variants ofTBX6cause a spectrum of phenotypes including CS and SCD, depending on the severity of the loss ofTBX6function.
Effects of halogen substituted on the Mn-O electron transfer of NiMn2O4
Authors: Li Hai-Long , Bian Liang , Dong Fa-Qin , Li Wei-Min , Zou Hao , Song Mian-Xin 
Published: April 2019

To observe the effect of halogen-substitution on the Mn-O electron transfer of NiMn2O4, we calculated Mn-mixed-valence configuration (charge-disproportionation) and oxygen vacancy by the density functional theory (DFT). The results indicate that the halogen-p5 state induces the O-2p orbital splitting to create an oxygen vacancy in the VB (valence band: about −5 eV). The oxygen vacancy can capture an electron from Mn[Formula: see text]-3d5 orbital that makes the Mn[Formula: see text]-3d5 change to Mn[Formula: see text]-3d4 states (Mn-charge disproportionate), and providing many effective-hole (40.14 [Formula: see text] 96.72 × 10[Formula: see text] kg). The halogen-p5-O-2p4 hybrid orbitals enhance the O-2p4-Mn-3d5 p-d hybrid orbital (about 19.18 electron). That increases the surface potential in Mn-O octahedron (for Cl-substituted: about 60 meV), the corresponding electron–electron interactions change from complex t[Formula: see text] (O-2p4-Mn[Formula: see text]-3d[Formula: see text] to complete [Formula: see text] (O-2p4-Mn[Formula: see text]-3d[Formula: see text]-e[Formula: see text](O-2p4-halogen-p5) orbital. This study effectively analyzes the microscopic changes of the electron transfer caused by the small amount of doping, provides a theoretical basis for the design of NMO-based semiconductor material.
Comparison of Questionnaire-Based Breast Cancer Prediction Models in the Nurses' Health Study
Authors: Glynn Robert J. , Colditz Graham A. , Tamimi Rulla M. , Chen Wendy Y. , Hankinson Susan E. , Willett Walter W. , Rosner Bernard 
Published: April 2019

Abstract

Background:
The Gail model and the model developed by Tyrer and Cuzick are two questionnaire-based approaches with demonstrated ability to predict development of breast cancer in a general population.

Methods:
We compared calibration, discrimination, and net reclassification of these models, using data from questionnaires sent every 2 years to 76,922 participants in the Nurses' Health Study between 1980 and 2006, with 4,384 incident invasive breast cancers identified by 2008 (median follow-up, 24 years; range, 1–28 years). In a random one third sample of women, we also compared the performance of these models with predictions from the Rosner–Colditz model estimated from the remaining participants.

Results:
Both the Gail and Tyrer–Cuzick models showed evidence of miscalibration (Hosmer–Lemeshow P &lt; 0.001 for each) with notable (P &lt; 0.01) overprediction in higher-risk women (2-year risk above about 1%) and underprediction in lower-risk women (risk below about 0.25%). The Tyrer–Cuzick model had slightly higher C-statistics both overall (P &lt; 0.001) and in age-specific comparisons than the Gail model (overall C, 0.63 for Tyrer–Cuzick vs. 0.61 for the Gail model). Evaluation of net reclassification did not favor either model. In the one third sample, the Rosner–Colditz model had better calibration and discrimination than the other two models. All models had C-statistics &lt;0.60 among women ages ≥70 years.

Conclusions:
Both the Gail and Tyrer–Cuzick models had some ability to discriminate breast cancer cases and noncases, but have limitations in their model fit.

Impact:
Refinements may be needed to questionnaire-based approaches to predict breast cancer in older and higher-risk women.
Predictive Value of HPV Testing in Self-collected and Clinician-Collected Samples Compared with Cytology in Detecting High-grade Cervical Lesions
Authors: El-Zein Mariam , Bouten Sheila , Louvanto Karolina , Gilbert Lucy , Gotlieb Walter H. , Hemmings Robert , Behr Marcel A. , Franco Eduardo L. ,   the CASSIS Study Group*
Published: April 2019

Abstract

Background:
Self-sampling has become an attractive proposition now that human papillomavirus (HPV) primary testing is being incorporated into cervical cancer screening programs worldwide. We compared predictive values of HPV testing based on self- and physician-collected samples, and cytology, in detecting high-grade cervical intraepithelial neoplasia (CIN).

Methods:
The Cervical And Self-Sample In Screening (CASSIS) study enrolled 1,217 women ages 16–70 years prior to scheduled colposcopies. Vaginal specimens were self-collected using the validated HerSwab device. Cervical specimens were collected by gynecologists. Specimens were tested for presence of high-risk HPV (hrHPV) by the Cobas 4800 HPV test. We estimated positive predictive values (PPV) and negative predictive values (NPV) and 95% confidence intervals (CI) for a subset of women (n = 700) who underwent cervical biopsy and cytology at the actual CASSIS visit.

Results:
hrHPV was detected in 329 women (47%) with HerSwab and in 327 (46.7%) with physician sampling. Respective values for HPV16/18 were 119 (17%) and 121 (17.3%). On histology, 134 women had CIN1, 49 had CIN2, 48 had CIN3, 5 had CIN2/CIN3, and 3 had cancers. PPVs for CIN2+ of any hrHPV were 28% (95% CI, 23.2–33.1) and 29.7% (95% CI, 24.8–34.9) for HerSwab and physician samples, respectively. Corresponding values for HPV16/18 were 43.7% (95% CI, 34.6–53.1) and 43.8% (95% CI, 34.8–53.1). PPV of cytology (ASC-US+) was 26.6% (95% CI, 21.6–32.0). Corresponding NPVs (same order as PPVs) were 96.4% (95% CI, 93.9–98.1), 97.8% (95% CI, 95.6–99), 90.9% (95% CI, 88.2–93.1), 91% (95% CI, 88.4–93.2), and 94.7% (95% CI, 91.8–96.8).

Conclusions:
Our results confirm that HPV self-sampling has comparable performance with a physician-collected sample in detecting cervical lesions.

Impact:
HPV self-sampling has the potential to increase coverage in cervical cancer screening.
OBI-3424, a Novel AKR1C3-Activated Prodrug, Exhibits Potent Efficacy against Preclinical Models of T-ALL
Authors: Evans Kathryn , Duan JianXin , Pritchard Tara , Jones Connor D. , McDermott Lisa , Gu Zhaohui , Toscan Cara E. , El-Zein Narimanne , Mayoh Chelsea , Erickson Stephen W. , Guo Yuelong , Meng Fanying , Jung Donald , Rathi Komal S. , Roberts Kathryn G. , Mullighan Charles G. , Shia Chi-Sheng , Pearce Tillman , Teicher Beverly A. , Smith Malcolm A. , Lock Richard B. 
Published: April 2019

Abstract

Purpose:
OBI-3424 is a highly selective prodrug that is converted by aldo-keto reductase family 1 member C3 (AKR1C3) to a potent DNA-alkylating agent. OBI-3424 has entered clinical testing for hepatocellular carcinoma and castrate-resistant prostate cancer, and it represents a potentially novel treatment for acute lymphoblastic leukemia (ALL).

Experimental Design:
We assessed AKR1C3 expression by RNA-Seq and immunoblotting, and evaluated the in vitro cytotoxicity of OBI-3424. We investigated the pharmacokinetics of OBI-3424 in mice and nonhuman primates, and assessed the in vivo efficacy of OBI-3424 against a large panel of patient-derived xenografts (PDX).

Results:
AKR1C3 mRNA expression was significantly higher in primary T-lineage ALL (T-ALL; n = 264) than B-lineage ALL (B-ALL; n = 1,740; P &lt; 0.0001), and OBI-3424 exerted potent cytotoxicity against T-ALL cell lines and PDXs. In vivo, OBI-3424 significantly prolonged the event-free survival (EFS) of nine of nine ALL PDXs by 17.1–77.8 days (treated/control values 2.5–14.0), and disease regression was observed in eight of nine PDXs. A significant reduction (P &lt; 0.0001) in bone marrow infiltration at day 28 was observed in four of six evaluable T-ALL PDXs. The importance of AKR1C3 in the in vivo response to OBI-3424 was verified using a B-ALL PDX that had been lentivirally transduced to stably overexpress AKR1C3. OBI-3424 combined with nelarabine resulted in prolongation of mouse EFS compared with each single agent alone in two T-ALL PDXs.

Conclusions:
OBI-3424 exerted profound in vivo efficacy against T-ALL PDXs derived predominantly from aggressive and fatal disease, and therefore may represent a novel treatment for aggressive and chemoresistant T-ALL in an AKR1C3 biomarker-driven clinical trial.
A Rationally Designed Peptide Antagonist of the PD-1 Signaling Pathway as an Immunomodulatory Agent for Cancer Therapy
Authors: Sasikumar Pottayil G. , Ramachandra Raghuveer K. , Adurthi Srinivas , Dhudashiya Amit A. , Vadlamani Sureshkumar , Vemula Koteswararao , Vunnum Sriharibabu , Satyam Leena K. , Samiulla Dodderi S. , Subbarao Krishnaprasad , Nair Rashmi , Shrimali Rajeev , Gowda Nagaraj , Ramachandra Murali 
Published: April 2019

AbstractPioneering success of antibodies targeting immune checkpoints such as PD-1 and CTLA4 has opened novel avenues for cancer immunotherapy. Along with impressive clinical activity, severe immune-related adverse events (irAE) due to the breaking of immune self-tolerance are becoming increasingly evident in antibody-based approaches. As a strategy to better manage severe adverse effects, we set out to discover an antagonist targeting PD-1 signaling pathway with a shorter pharmacokinetic profile. Herein, we describe a peptide antagonist NP-12 that displays equipotent antagonism toward PD-L1 and PD-L2 in rescue of lymphocyte proliferation and effector functions. In preclinical models of melanoma, colon cancer, and kidney cancers, NP-12 showed significant efficacy comparable with commercially available PD-1–targeting antibodies in inhibiting primary tumor growth and metastasis. Interestingly, antitumor activity of NP-12 in a preestablished CT26 model correlated well with pharmacodynamic effects as indicated by intratumoral recruitment of CD4 and CD8 T cells, and a reduction in PD-1+ T cells (both CD4 and CD8) in tumor and blood. In addition, NP-12 also showed additive antitumor activity in preestablished tumor models when combined with tumor vaccination or a chemotherapeutic agent such as cyclophosphamide known to induce “immunologic cell death.” In summary, NP-12 is the first rationally designed peptide therapeutic targeting PD-1 signaling pathways exhibiting immune activation, excellent antitumor activity, and potential for better management of irAEs.