bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Reciprocity between Radiotherapy and Cancer Immunotherapy
Authors: Wang Yifan , Liu Zhi-Gang , Yuan Hengfeng , Deng Weiye , Li Jing , Huang Yuhui , Kim Betty Y.S. , Story Michael D. , Jiang Wen 
Published: November 2018

Abstract
The clinical success of immune checkpoint inhibitors in treating metastatic and refractory cancers has generated significant interest in investigating their role in treating locally advanced diseases, thus requiring them to be combined with standard treatments in the hope of producing synergistic antitumor responses. Radiotherapy, in particular, has long been hypothesized to have actions complementary to those of immune checkpoint blockade, and a growing body of evidence indicates that cancer immunotherapy may also have radiosensitizing effects, which would provide unique benefit for locoregional treatments. Recent studies have demonstrated that when immune cells are activated by immunotherapeutics, they can reprogram the tumor microenvironment in ways that may potentially increase the radiosensitivity of the tumor. In this review, we highlight the evidence that supports reciprocal interactions between cancer immunotherapy and radiotherapy, where in addition to the traditional notion that radiation serves to enhance the activation of antitumor immunity, an alternative scenario also exists in which T-cell activation by cancer immunotherapy may sensitize tumors to radiation treatment through mechanisms that include normalization of the tumor vasculature and tissue hypoxia. We describe the empirical observations from preclinical models that support such effects and discuss their implications for future research and trial design.
Predicting Outcome in Head and Neck Cancer: miRNAs with Potentially Big Effects
Authors: Clump David A. , Pickering Curtis R. , Skinner Heath D. 
Published: November 2018

AbstractA five-miRNA signature for human papillomavirus (HPV)–negative head and neck squamous cell carcinoma (HNSCC) identifies patients at risk for inferior outcomes. Combining established clinical variables with this novel miRNA signature affords an opportunity to personalize and intensify treatment strategies in this high-risk patient population.See related article by Hess et al., p. 1505
Urolithin A, a Novel Natural Compound to Target PI3K/AKT/mTOR Pathway in Pancreatic Cancer
Authors: Totiger Tulasigeri M. , Srinivasan Supriya , Jala Venkatakrishna R. , Lamichhane Purushottam , Dosch Austin R. , Gaidarski Alexander A. , Joshi Chandrashekhar , Rangappa Shobith , Castellanos Jason , Vemula Praveen Kumar , Chen Xi , Kwon Deukwoo , Kashikar Nilesh , VanSaun Michael , Merchant Nipun B. , Nagathihalli Nagaraj S. 
Published: November 2018

Abstract
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy and is highly resistant to standard treatment regimens. Targeted therapies against KRAS, a mutation present in an overwhelming majority of PDAC cases, have been largely ineffective. However, inhibition of downstream components in the KRAS signaling cascade provides promising therapeutic targets in the management of PDAC and warrants further exploration. Here, we investigated Urolithin A (Uro A), a novel natural compound derived from pomegranates, which targets numerous kinases downstream of KRAS, in particular the PI3K/AKT/mTOR signaling pathways. We showed that treatment of PDAC cells with Uro A blocked the phosphorylation of AKT and p70S6K in vitro, successfully inhibited the growth of tumor xenografts, and increased overall survival of Ptf1aCre/+;LSL-KrasG12D/+;Tgfbr2flox/flox (PKT) mice compared with vehicle or gemcitabine therapy alone. Histologic evaluation of these Uro A–treated tumor samples confirmed mechanistic actions of Uro A via decreased phosphorylation of AKT and p70S6K, reduced proliferation, and increased cellular apoptosis in both xenograft and PKT mouse models. In addition, Uro A treatment reprogrammed the tumor microenvironment, as evidenced by reduced levels of infiltrating immunosuppressive cell populations such as myeloid-derived suppressor cells, tumor-associated macrophages, and regulatory T cells. Overall, this work provides convincing preclinical evidence for the utility of Uro A as a therapeutic agent in PDAC through suppression of the PI3K/AKT/mTOR pathway.
Two unrecorded penaeid shrimp species of the genus Parapenaeus (Decapoda, Dendrobranchiata) from Korean waters
Authors: Kim Jung Nyun , Choi Jung Hwa 
Published: November 2018

Abstract
Two Parapenaeus species, P. australiensis Dall, 1957 and P. fissurus (Spence Bate, 1881), collected from around Jeju Island and east of Busan, southern Korean waters, are briefly described here. Both species are newly recorded from Korean waters, with the former record representing a considerable range extension from the tropical western Pacific to the northern East China Sea. Distributional and morphological accounts of these species are presented.
Geographically structured genetic variation in Ptychozoon lionotum (Squamata: Gekkonidae) and a new species from an isolated volcano in Myanmar
Authors: GRISMER L. LEE , WOOD PERRY L. JR. , THURA MYINT KYAW , GRISMER MARTA S. , BROWN RAFE M. , STUART BRYAN L. 
Published: November 2018

A molecular phylogenetic analysis of Parachute Geckos (Genus Ptychozoon Kuhl & van Hasselt, 1822) based on the mitochondrial gene ND2 indicates that a newly discovered population from the Mt. Popa volcano—a habitat island in the northern portion of the Bago Yoma mountains, Myanmar—is a new species, P. popaense sp. nov. This species is part of a clade that contains P. bannanense Wang, Wang, & Liu, 2016 and P. lionotum Annandale, 1905 of Indochina. Ptychozoon popaense sp. nov. is morphologically most similar to its sister species P. lionotum which manifests considerable geographic substructuring of genetic variation but differs from the nominate taxon by an uncorrected pairwise sequence divergence of 16.0–17.1% and by discrete differences in morphology and color pattern. This discovery highlights the unique, insular nature of the Bago Yoma mountains of the Ayeyarwady Basin, which support other endemic gekkonids. It also underscores the growing diversity in this highly derived clade of cryptic, parachuting, geckos characterized by highly divergent genetic lineages, which may indicate the presence of additional, unrecognized species.
The Role of the Nonlinearity of the Stefan–Boltzmann Law on the Structure of Radiatively Forced Temperature Change
Authors: Henry Matthew , Merlis Timothy M. 
Published: November 2018

AbstractThe Stefan–Boltzmann law governs the temperature dependence of the blackbody emission of radiation: . A consequence of this nonlinearity is that a cold object needs a greater increase in temperature than a hot object in order to reach the same increase in radiation emitted. Therefore, this nonlinearity potentially has an impact on the structure of radiatively forced atmospheric temperature change in both the horizontal and vertical directions. For example, it has previously been argued to be a cause of polar amplification (PA) of surface air warming. Here, the role of this nonlinearity is investigated by 1) assessing the magnitude of its effect on PA compared to spatial variations in CO2’s radiative forcing for Earth’s atmosphere and 2) linearizing in a gray radiation atmospheric general circulation model (GCM) with an interactive hydrological cycle. Estimates for Earth’s atmosphere show that the combination of the Planck feedback and forcing from CO2 would produce a tropically amplified warming if they were the only means of changing the Earth’s energy balance. Contrary to expectations, climate change simulations with linearized radiation do not have reduced polar amplification of surface air warming relative to the standard GCM configuration. However, simulations with linearized radiation consistently show less warming in the upper troposphere and more warming in the lower troposphere across latitudes. The lapse rate feedbacks from pure radiative and radiative–convective configurations of the model are used to show that the “cold-altitudes-warm-more” effect of the nonlinearity carries across this model hierarchy.
Shar Pei Larynx: Supraglottic and Postcricoid Mucosal Redundancy and Its Association With Medical Comorbidities
Authors: Yiu Yin , Tibbetts Kathleen M. , Simpson C. Blake , Matrka Laura A. 
Published: November 2018

Objectives: The aim of this study is to describe a clinical entity the authors term “Shar Pei larynx,” characterized by redundant supraglottic and postcricoid mucosa that the authors hypothesize coexists in patients with obstructive sleep apnea, laryngopharyngeal reflux, and obesity. By exploring this hypothesis, the authors hope to set the foundation for future research with the goal of identifying whether Shar Pei larynx is a marker for untreated sleep apnea or other diseases. Study Design: Retrospective chart review. Setting: Two tertiary care academic institutions. Methods: Data were collected from a 5-year period by querying for patients described to have “Shar Pei larynx” or “posterior supraglottic and/or postcricoid mucosal redundancy” on laryngoscopic findings. Relevant demographic and clinical characteristics were analyzed, with a focus on associations with obesity, sleep apnea, and laryngopharyngeal reflux. Results: Thirty-two patients were identified with physical findings consistent with Shar Pei larynx. Twenty-six patients (81.3%) were obese; 16 (50%) were morbidly obese. Twenty-two patients (68.8%) either had an existing diagnosis of obstructive sleep apnea or were diagnosed on polysomnography performed after initial evaluation. Sixteen patients (50%) had type 2 diabetes mellitus, and 87.5% of these patients were obese. Twenty-eight patients (87.5%) noted histories of reflux, with a median reflux symptom index of 27 of 45. Five patients underwent procedures to reduce mucosal redundancy related to Shar Pei larynx. Conclusions: This pilot study confirms that the majority of patients diagnosed with Shar Pei larynx also had diagnoses of obesity, obstructive sleep apnea, and reflux disease. The demonstrated association is strong enough to warrant further study.
French validation of the Arthritis Self-Efficacy Scale and further psychometric properties exploration among 168 people with osteoarthritis
Authors: Bareyre Loïc , Gay Chloé , Coste Nicolas , Bonnin Armand , Pereira Bruno , Coudeyre Emmanuel 
Published: November 2018

Objective: To validate the Arthritis Self-Efficacy Scale—French version (ASES-F) of the ASES questionnaire designed to evaluate self-efficacy in arthritis population and to confirm its psychometric properties. Design: The translation/back-translation procedure was done in line with cross-cultural adaptation international guidelines. Prospective multicenter validation was performed on 168 patients with osteoarthritis who filled out the ASES-F. Function subscale of the Western Ontario and McMaster Universities Arthritis Index, Hospital Anxiety and Depression (HAD), Knee Osteoarthritis Fears and Beliefs Questionnaire, and pain on visual analog scale were collected. Acceptability, internal consistency, reproducibility, internal and external structure validity, and sensitivity following a self-management program focused on physical activity were analyzed. The retest was performed 15 days later. Results: A culturally adapted version was obtained following the validation procedure. The final translated questionnaire is available within the full article. Cronbach’s alpha coefficient was at 0.95 for the overall ASES-F. Regarding the test–retest reproducibility, Lin’s concordance coefficient was at 0.84. The internal and external validity was also explored with correlations at −0.50 between ASES-F and (WOMAC), and significant correlations between ASES-F and HAD. Sensitivity shown significant improvement at three months for the subscale function only (+2.65, P < 0.01). Conclusion: The ASES-F, French version of the ASES, available in supplemental data, was validated in knee osteoarthritis patients and could be used in clinical practice and research for French-speaking patients. Sensitivity needs to be more explored.
Post traumatic headache (PTH) in a cohort of UK compensation claimants
Authors: Lane Russell , Davies Paul 
Published: November 2018

Aim To explore post traumatic headache characteristics and risk factors in compensation claimants by observational retrospective cohort analysis. Case results Medicolegal reports on 116 consecutive compensation claimants aged 41.9 ± 15.0 years were reviewed 21 ± 14 months after injury. Eighty eight had suffered head and neck injuries, 21 reported only neck injury and seven had “other injuries”. Ninety four percent of the head injuries were “mild”. The incidence of post traumatic headache following neck injury did not differ from that following head and neck injury, and none of the “other injuries” cases developed post traumatic headache. We anticipated that all head and neck injury claimants would seek compensation for post traumatic headache, but 25% denied developing headache. Post traumatic headache was very strongly correlated with a past history of primary headache ( p < 0.0001) but no other risk factors were identified. Post traumatic headache semiology was consistent with “migraine” or “probable migraine” in 90% of cases. Headache resolved in 30% of claimants between 3 and 24 months after injury but 70% continued to suffer headaches at the time of assessment. Forty one percent of claimants had received no treatment for post traumatic headache in primary care. Conclusions Our data suggest that post traumatic headache is essentially “migraine” provoked by head or neck concussion. It is not clear why so many post traumatic headache sufferers receive poor or inadequate treatment for this condition.
The Impact of the Hai Yang Shi You 981 Event on Vietnam’s Stock Markets
Authors: Le Thai-Ha , Park Donghyun , Tran Cong-Phu-Khanh , Tran-Nam Binh 
Published: November 2018

This study examines the extent to which the Hai Yang Shi You 981 (HD-981) event, the sudden deployment of a Chinese oil rig in disputed territorial waters near Paracel Islands in May 2014, affected the stock market performance of 20 sectors of the Vietnamese economy. The impact was measured in terms of stock returns, using daily data on stock market indices. The results strongly indicate that the HD-981 event significantly and negatively affected the overall performance of Vietnam’s stock markets. There is, however, considerable variation across sectors. While most sectors which are heavily dependent on the economy of China were adversely affected, the impact on some sectors was negligible. By conducting this study on Vietnam’s stock markets, we hope to generate implications and lessons for other emerging markets in the region. JEL Classification: G1, G14, C58
Changing goals and guidelines
Authors: Wood David 
Published: November 2018

The Joint British Societies guidelines on the prevention of coronary heart disease (CHD) are being revised. Target populations will be patients with any symptomatic presentation of atherosclerotic disease, whatever the vascular territory. The first-degree relatives of patients with premature cardiovascular disease also need to be targeted. Third, individuals at high multifactorial risk of developing cardiovascular disease need to be targeted. New risk prediction charts are being produced. Patients with a cardiovascular risk of ≥ 20% over 10 years (equivalent to a CHD risk of 15% over 10 years) will require investigation and treatment to blood pressure and lipid targets. Those with a cardiovascular disease risk below this threshold require lifestyle advice.
Targeting multiple pathways in cholesterol management
Authors: Wierzbicki Anthony 
Published: November 2018

There is a wide variation in plasma total cholesterol levels in populations that are genetically similar: these variations are driven by the environment. We absorb 40—50% of our cholesterol from the diet, and synthesise 50—60% in the liver. Cholesterol absorption inhibitors target the exogenous pathway of cholesterol absorption. Agents that act on different pathways in cholesterol metabolism, such as statins and cholesterol absorption inhibitors, can be co-administered in an attempt to achieve complementary or synergistic effects on lipid control.
The role of dyslipidaemia in coronary heart disease
Authors: Wierzbicki Anthony S 
Published: November 2018

The role of cholesterol in cardiovascular disease (CVD) and especially coronary heart disease (CHD) is well established. Epidemiological studies show consistent relationships between total cholesterol, low-density lipoprotein cholesterol (LDL-C) and CHD risk. These same studies show a strong inverse relationship for levels of high-density lipoprotein cholesterol (HDL-C) and CHD risk and a possible relationship for triglycerides. The metabolic syndrome is a common syndrome affecting 20—25% of the population whose features include abdominal obesity, low-HDL-C, elevated triglycerides, hypertension, hyperglycaemia, hyperinsulinaemia, elevated inflammatory markers, renal dysfunction and microalbuminuria. In the UKPDS study in type 2 diabetes that compared the effects of improved glycaemic and blood pressure control, though some benefit was seen on cardiovascular end points with tighter control, the critical factors predisposing to later macrovascular disease were LDL-C and HDL-C. There is extensive trial evidence for the benefits of statins in secondary and primary prevention. All guidelines state these are first-line agents for the treatment of cardiovascular risk. Statins have undoubted benefits in the treatment of patients with type 2 diabetes. Statins are also effective in reducing CVD in patients with metabolic syndrome. However, the focus on the benefits of statin therapy has limited discussion of their limitations. In all statin trials to date they reduce CVD events by 25—30% with the largest reduction in the GREACE study being 50%. Only high-dose statin therapy prevents progression of atherosclerosis. Thus, a single minded concentration on LDL-C may underestimate the benefits of a more integrated approach to the management of hyperlipidaemia.
Pregnancy outcomes among women with type 1 diabetes mellitus using continuous subcutaneous insulin infusion versus multiple daily injections: A retrospective cohort study
Authors: Dixon Benjamin RS , Nankervis Alison , Hopkins Stephanie CN , Cade Thomas J 
Published: November 2018

Background Insulin delivery options for pregnant women with type 1 diabetes mellitus are either continuous subcutaneous insulin infusion or multiple daily injections. The aim of this paper is to compare pregnancy outcomes in women with type 1 diabetes mellitus using continuous subcutaneous insulin infusion or multiple daily injections in pregnancy. Methods Retrospective single-centre cohort study of 298 pregnancies booked between 2006 and 2016. Descriptive analysis was performed for HbA1c values. Logistic regression models were created to compare selected maternal and neonatal outcomes. Results Continuous subcutaneous insulin infusion was associated with increased risk of large-for-gestational age (aOR 2.00, 95% CI 1.20–3.34) and preterm neonates (aOR 1.80, 95% CI 1.04–3.03). Continuous subcutaneous insulin infusion had no association with increased risk of adverse pregnancy outcomes. No difference in HbA1c values existed between groups. Conclusion Using continuous subcutaneous insulin infusion for type 1 diabetes mellitus through pregnancy is associated with increased risk of large-for-gestational age and preterm neonates, without increased risk of associated adverse maternal or neonatal outcomes.
Phase Ib/II single-arm trial evaluating the combination of everolimus, lapatinib and capecitabine for the treatment of HER2-positive breast cancer with brain metastases (TRIO-US B-09)
Authors: Hurvitz Sara , Singh Rashi , Adams Brad , Taguchi Julie A. , Chan David , Dichmann Robert A. , Castrellon Aurelio , Hu Eddie , Berkowitz Jonathan , Mani Aruna , DiCarlo Brian , Callahan Rena , Smalberg Ira , Wang Xiaoyan , Meglar Ivana , Martinez Diego , Hobbs Evthokia , Slamon Dennis J. 
Published: November 2018

Background: Improving outcomes for patients with human epidermal growth factor 2-positive (HER2+) central nervous system (CNS) metastases remains an unmet clinical need. This trial evaluated a novel combination of everolimus, lapatinib and capecitabine for this disease. Methods: Patients with trastuzumab-pretreated, HER2+ breast cancer brain metastasis without prior therapy with a mammalian target of rapamycin (mTOR) inhibitor were eligible. Patients received lapatinib and everolimus daily (continuously) and capecitabine twice daily (d1–14) in 21-d cycles. The primary endpoint was the 12-week CNS objective response rate (ORR). Secondary endpoints included safety, progression-free survival (PFS), overall survival (OS), best CNS ORR and extra-CNS ORR. Results: A total of 19 participants were enrolled and treated with ⩾1 dose of the study drug. The median age was 58.5 years, the median number of therapies for metastatic breast cancer was 2.5 (0–11). Pretrial, 74% of participants had received prior lapatinib, capecitabine or both. A total of 63% had received previous CNS radiation or surgical resection and CNS radiation. The maximum tolerated doses were lapatinib at 1000 mg, everolimus at 10 mg, and capecitabine at 1000 mg/m2. Phase II proceeded with capecitabine at 750 mg/m2 due to better tolerability. The most common grade 3/4 adverse events were mucositis (16%), diarrhea, fatigue, and hypokalemia (11% each). Of 11 participants evaluable for 12-week CNS ORR, 3 (27%) had partial response and 7 (64%) had stable disease. The best CNS ORR in eligible participants was 28% (5/18). The median PFS and OS were 6.2 and 24.2 months, respectively. Conclusions: This novel triplet combination of lapatinib, everolimus, and capecitabine is well tolerated and yielded a 27% response rate in the CNS at 12 weeks in heavily pretreated participants. Larger studies are warranted to further evaluate this regimen. Trial registration: ClinicalTrials.gov: NCT01783756. Registered 05 February 2013, https://clinicaltrials.gov/ct2/show/NCT01783756