bluuebunny/crossref_metadata_2025_split huggingface dataset:
Polygenic and multifactorial scores for pancreatic ductal adenocarcinoma risk prediction
Authors: Galeotti Alice Alessandra , Gentiluomo Manuel , Rizzato Cosmeri , Obazee Ofure , Neoptolemos John P , Pasquali Claudio , Nentwich Michael , Cavestro Giulia Martina , Pezzilli Raffaele , Greenhalf William , Holleczek Bernd , Schroeder Cornelia , Schöttker Ben , Ivanauskas Audrius , Ginocchi Laura , Key Timothy J , Hegyi Péter , Archibugi Livia , Darvasi Erika , Basso Daniela , Sperti Cosimo , Bijlsma Maarten F , Palmieri Orazio , Hlavac Viktor , Talar-Wojnarowska Renata , Mohelnikova-Duchonova Beatrice , Hackert Thilo , Vashist Yogesh , Strouhal Ondrej , van Laarhoven Hanneke , Tavano Francesca , Lovecek Martin , Dervenis Christos , Izbéki Ferenc , Padoan Andrea , Małecka-Panas Ewa , Maiello Evaristo , Vanella Giuseppe , Capurso Gabriele , Izbicki Jakob R , Theodoropoulos George E , Jamroziak Krzysztof , Katzke Verena , Kaaks Rudolf , Mambrini Andrea , Papanikolaou Ioannis S , Szmola Richárd , Szentesi Andrea , Kupcinskas Juozas , Bursi Simona , Costello Eithne , Boggi Ugo , Milanetto Anna Caterina , Landi Stefano , Gazouli Maria , Vodickova Ludmila , Soucek Pavel , Gioffreda Domenica , Gemignani Federica , Brenner Hermann , Strobel Oliver , Büchler Markus , Vodicka Pavel , Paiella Salvatore , Canzian Federico , Campa Daniele 
Published: June 2020

BackgroundMost cases of pancreatic ductal adenocarcinoma (PDAC) are asymptomatic in early stages, and the disease is typically diagnosed in advanced phases, resulting in very high mortality. Tools to identify individuals at high risk of developing PDAC would be useful to improve chances of early detection.ObjectiveWe generated a polygenic risk score (PRS) for PDAC risk prediction, combining the effect of known risk SNPs, and carried out an exploratory analysis of a multifactorial score.MethodsWe tested the associations of the individual known risk SNPs on up to 2851 PDAC cases and 4810 controls of European origin from the PANcreatic Disease ReseArch (PANDoRA) consortium. Thirty risk SNPs were included in a PRS, which was computed on the subset of subjects that had 100% call rate, consisting of 839 cases and 2040 controls in PANDoRA and 6420 cases and 4889 controls from the previously published Pancreatic Cancer Cohort Consortium I–III and Pancreatic Cancer Case-Control Consortium genome-wide association studies. Additional exploratory multifactorial scores were constructed by complementing the genetic score with smoking and diabetes.ResultsThe scores were associated with increased PDAC risk and reached high statistical significance (OR=2.70, 95% CI 1.99 to 3.68, p=2.54×10−10 highest vs lowest quintile of the weighted PRS, and OR=14.37, 95% CI 5.57 to 37.09, p=3.64×10−8, highest vs lowest quintile of the weighted multifactorial score).ConclusionWe found a highly significant association between a PRS and PDAC risk, which explains more than individual SNPs and is a step forward in the direction of the construction of a tool for risk stratification in the population.
Photodissociation of mono- and di-anionic tin clusters
Authors: Wolfram Markus , Bandelow Steffi , Jankowski Alexander , König Stephan , Marx Gerrit , Schweikhard Lutz 
Published: June 2020

Abstract

Negatively charged tin clusters offer a broad range of decay products, as observed after electron-cluster interactions [S. König, M. Wolfram, S. Bandelow, G. Marx, L. Schweikhard, Eur. Phys. J. D 72, 153 (2018)]. To get further insight into their decay pathways, size and charge-state selected clusters Snn- and Snn2- were photo-excited at the ClusterTrap setup by 532 nm Nd:YAG laser pulses. For small mono-anionic precursor clusters containing up to n ≃ 45 atoms, Snn-7- and Snn-10- are observed as preferred ionic fragments. For bigger clusters a transition to neutral monomer evaporation was found. In the case of di-anionic precursors, preferred decay products are Sn10- and Snn-10-, indicating fission similar to the case of the group 14 neighbor element lead [S. König, A. Jankowski, G. Marx, L. Schweikhard, M. Wolfram, Phys. Rev. Lett. 120, 163001 (2018)]. Furthermore, doubly charged fragment clusters such as Snn-72- are observed, originating from break-off of neutral heptamers Sn7, a behavior which has not been observed previously for di-anionic clusters.

Graphical abstract
Rb and p53 Execute Distinct Roles in the Development of Pancreatic Neuroendocrine Tumors
Authors: Yamauchi Yuki , Kodama Yuzo , Shiokawa Masahiro , Kakiuchi Nobuyuki , Marui Saiko , Kuwada Takeshi , Sogabe Yuko , Tomono Teruko , Mima Atsushi , Morita Toshihiro , Matsumori Tomoaki , Ueda Tatsuki , Tsuda Motoyuki , Nishikawa Yoshihiro , Kuriyama Katsutoshi , Sakuma Yojiro , Ota Yuji , Maruno Takahisa , Uza Norimitsu , Masuda Atsuhiro , Tatsuoka Hisato , Yabe Daisuke , Minamiguchi Sachiko , Masui Toshihiko , Inagaki Nobuya , Uemoto Shinji , Chiba Tsutomu , Seno Hiroshi 
Published: June 2020

Abstract

Pancreatic neuroendocrine tumors (PanNET) were classified into grades (G) 1 to 3 by the World Health Organization in 2017, but the precise mechanisms of PanNET initiation and progression have remained unclear. In this study, we used a genetically engineered mouse model to investigate the mechanisms of PanNET formation. Although pancreas-specific deletion of the Rb gene (Pdx1-Cre;Rbf/f) in mice did not affect pancreatic exocrine cells, the α-cell/β-cell ratio of islet cells was decreased at 8 months of age. During long-term observation (18–20 months), mice formed well-differentiated PanNET with a Ki67-labeling index of 2.7%. In contrast, pancreas-specific induction of a p53 mutation (Pdx1-Cre;Trp53R172H) had no effect on pancreatic exocrine and endocrine tissues, but simultaneous induction of a p53 mutation with Rb gene deletion (Pdx1-Cre;Trp53R172H;Rb f/f) resulted in the formation of aggressive PanNET with a Ki67-labeling index of 24.7% over the short-term (4 months). In Pdx1-Cre;Trp53R172H;Rbf/f mice, mRNA expression of Pten and Tsc2, negative regulators of the mTOR pathway, significantly decreased in the islet cells, and activation of the mTOR pathway was confirmed in subsequently formed PanNET. Thus, by manipulating Rb and p53 genes, we established a multistep progression model from dysplastic islet to indolent PanNET and aggressive metastatic PanNET in mice. These observations suggest that Rb and p53 have distinct roles in the development of PanNET.

Significance:
Pancreas-specific manipulation of Rb and p53 genes induced malignant transformation of islet cells, reproducing stepwise progression from microadenomas to indolent (grade 1) and subsequent aggressive PanNETs (grade 2–3).
Interaction with CD68 and Regulation of GAS6 Expression by Endosialin in Fibroblasts Drives Recruitment and Polarization of Macrophages in Hepatocellular Carcinoma
Authors: Yang Fa , Wei Yan , Han Donghui , Li Yu , Shi Shengjia , Jiao Dian , Wu Jieheng , Zhang Qiang , Shi Changhong , Yang Lijun , Song Wei , Zhang Jingliang , Han Yueheng , Zhang Rui , Yang An-Gang , Dimitrov Dimiter S. , Zhao Aizhi , Qin Weijun , Wen Weihong 
Published: June 2020

Abstract

Fibroblasts and macrophages play key roles in the development of hepatocellular carcinoma (HCC). However, cross-talk between these two kinds of cells has not been well studied. Endosialin (CD248/TEM1) is a transmembrane glycoprotein that is expressed in certain cancer cells, tumor stromal cells, and pericytes. In this study, we found that endosialin is mainly expressed in cancer-associated fibroblasts (CAF) in HCC and its expression inversely correlates with patient prognosis. Endosialin interacted with CD68 to recruit macrophages and regulated expression of GAS6 in CAFs to mediate M2 polarization of macrophages. The fully human antibody IgG78 bound glycosylated endosialin and induced its internalization in CAFs, thus weakening the cross-talk between CAFs and macrophages. In subcutaneous and orthotopic xenograft models of HCC in nude mice, treatment with IgG78 significantly inhibited tumor growth. These results indicate that endosialin-positive CAFs promote HCC progression and highlight IgG78 as a promising therapeutic candidate for HCC treatment.

Significance:
These findings highlight CAF-expressed endosialin as a primary regulator of macrophage recruitment and polarization and demonstrate endosialin inhibition as a potential treatment strategy for HCC.
Inhibition of Aurora-A Promotes CD8+ T-Cell Infiltration by Mediating IL10 Production in Cancer Cells
Authors: Han Jing , Jiang Zhen , Wang Chennan , Chen Xin , Li Rongqing , Sun Na , Liu Xiangye , Wang Hui , Hong Li , Zheng Kuiyang , Yang Jing , Ikezoe Takayuki 
Published: June 2020

AbstractIntratumoral tumor-specific activated CD8+ T cells with functions in antitumor immune surveillance predict metastasis and clinical outcome in human colorectal cancer. Intratumoral CD8+ T cells also affect treatment with immune checkpoint inhibitors. Interestingly, inhibition of Aurora kinase A (Aurora-A) by its selective inhibitor alisertib obviously induced infiltration of CD8+ T cells. However, the mechanisms by which inhibition of Aurora-A promotes infiltration of intratumoral CD8+ T cells remain unclear. Our recent results demonstrated that conditional deletion of the AURKA gene or blockade of Aurora-A by alisertib slowed tumor growth in association with an increase in the infiltration of intratumoral CD8+ T cells as well as the mRNA levels of their IL10 receptor α (IL10Rα). The antitumor effects of targeting Aurora-A were attenuated in the absence of CD8+ T cells. In addition, antibody-mediated blockade of IL10Rα dramatically decreased the percentage of intratumoral CD8+ T cells. In further experiments, we found that the levels of IL10 were elevated in the serum of azoxymethane/dextran sodium sulfate-treated AURKAflox/+;VillinCre+ mice. Unexpectedly, we found that in addition to Aurora-A's mitotic role, inhibition of Aurora-A elevated IL10 transcription, which in turn increased the IL10Rα mRNA levels in CD8+ T cells. Thus, inhibition of Aurora-A could be a useful treatment strategy for recruiting tumor-specific intratumoral CD8+ T cells.Implications:Understanding the mechanisms by which inhibition of Aurora-A promotes CD8+ T-cell infiltration and activation, as mediated by the IL10 pathway could provide a potential strategy for tumor immunotherapy.
Phytodiversity of chasmophytic habitats at Olichuchattam Waterfalls, Kerala, India
Authors: Arun Christy  , Thomas Binu 
Published: June 2020

The present study was conducted to analyse the Phytodiversity of Chasmophytic habitats at Olichuchattam waterfalls, Kerala, India. The studies on the plants in such special type of habitats are very less. Hence the present study will help to know more about them. Field exploration and observations were made, plants were collected, identified and herbarium was prepared. Analysis of plants and soil samples from different regions of the study area based on altitudinal variations was also done. As a result of the study, a total of 120 plant species that belonging to 49 families and 93 genera were documented. Of these 5 species are bryophyte, 10 species are pteridophytes and 105 species are angiosperms. The ornamental potentiality of the plants in the study area was also analysed and it shows that a total of 47 species have ornamental potentialities. The present study also highlighted some threatening factors can affect the distribution of plants in the present study area. The present study highlights that, the rocky cliffs and crevices serves as an excellent habitat for many interesting plant groups. The plants in these habitats are very unique and are attractive.The rocky cliffs and crevices represents a good indicator of rich biodiversity within small areas.
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Osteological description of Indian Skipper Frog Euphlyctis cyanophlyctis (Anura: Dicroglossidae) from the Western Ghats of India
Authors: Gorule Pankaj A. , Gosavi Sachin M. , Kharat Sanjay , Verma Chandani 
Published: June 2020

The present study provides description of the osteology of Skipper Frog Euphlyctis cyanophlyctis. Seven adult specimens of E. cyanophlyctis from northern Western Ghats of India were cleared and double stained for studying osteological characteristics. The baseline description of osteological characters of cranial and post-cranial elements (paired nasals, tubular sphenethmoid, well-developed vomerine teeth, arciferal pectoral girdle, fan-shaped omosternum, cartilaginous W-shaped xiphisternum, hind limb with longest cylindrical humerus, V-shaped pectoral girdle and phalangeal appendages) provided in present study will help in further taxonomic investigations of the genus Euphlyctis. Further, the baseline information on osteology of Skipper frog will serve as a reference material for investigations related to malformations, either in this or related species. We also provide first observation on sacro-pelvic malformation in one of the studied specimens.
Corrigendum to A citizens science approach to monitoring of the Lion Panthera leo (Carnivora: Felidae) population in Niokolo-Koba National Park, Senegal
Authors: Dimitri Dagorne  , Abdoulaye Kanté  , Rose John B. 
Published: June 2020

Following publication of this article on 26 January 2020 (Journal of Threatened Taxa 12(1): 15091–15105), the authors were able to re-examine all of the collected photographs with Sara Blackburn, a expert in lion identification. A corrected section on Identification of individual lions is reproduced below; no other parts of the article require correction.
Virome Sequencing in Patients With Myocarditis
Authors: Heidecker Bettina , Williams Simon H. , Jain Komal , Oleynik Alexandra , Patriki Dimitri , Kottwitz Jan , Berg Jan , Garcia Joel A. , Baltensperger Nora , Lovrinovic Marina , Baltensweiler Andrea , Mishra Nishay , Briese Thomas , Hanson Paul J. , Lauten Alexander , Poller Wolfgang , Leistner David M. , Landmesser Ulf , Enseleit Frank , McManus Bruce , Lüscher Thomas F. , Lipkin W. Ian 
Published: June 2020

Background:
Polymerase chain reaction analyses of cardiac tissues have detected viral sequences in up to 67% of cases of myocarditis. However, viruses have not been implicated in giant cell myocarditis (GCM). Furthermore, efforts to detect viruses implicated in myocarditis have been unsuccessful in more accessible samples such as peripheral blood.

Methods:
We used Virome Capture Sequencing for Vertbrate Viruses (VirCapSeq-VERT), a method that simultaneously screens for all known vertebrate viruses, to investigate viruses in 33 patients with myocarditis. We investigated peripheral blood mononuclear cells (n=24), plasma (n=27), endomyocardial biopsies (n=2), and cardiac tissue samples from explanted hearts (n=13).

Results:
Nine patients (27%) had GCM and 4 patients (13%) had fulminant myocarditis. We found the following viruses in the blood of patients with myocarditis: Epstein Barr virus (n=11, 41%), human pegivirus (n=1, 4%), human endogenous retrovirus K (n=27, 100%), and anellovirus (n=15, 56%). All tissue samples from fulminant myocarditis (n=2) and GCM (n=13) contained human endogenous retrovirus K.

Conclusions:
No nucleic acids from viruses previously implicated in myocarditis or other human illnesses were detected in relevant amounts in cardiac tissue samples from GCM or in blood samples from other types of myocarditis. These findings do not exclude a role for viral infection in GCM but do suggest that if viruses are implicated, the mechanism is likely to be indirect rather than due to cytotoxic infection of myocardium.
Religious Studies for Cyborgs: Cognitive Science and Social Theory after Humanism
Authors: Simmons K. Merinda 
Published: June 2020

Abstract
As it appears, the back and forth between CSR and critical theory pays a great deal of attention to religion as a classificatory and explanatory object but has thus far left alone another category—that of the human. Scholars in other fields, however, have long demonstrated the human subject to be a slippery trope all its own whose rhetorical and analytical value is not at all a given. It is on the evolution and contemporary state of this vein of criticism that I will focus, then, in an attempt to shift the register of the current conversation about CSR.
A Referral Process to the Commission on the Limits of the Continental Shelf in the Delimitation of the Continental Shelf beyond 200 M Process: An Appraisal
Authors: De Herdt Sandrine W 
Published: June 2020

Abstract
Proposals have been flagged by judges at the International Tribunal for the Law of the Sea and legal scholars to develop the relationship between the Commission on the Limits of the Continental Shelf (CLCS) and international courts and tribunals regarding the proof of existence of continental shelf entitlement. It has been suggested international courts and tribunals request ‘expert assistance’, make a ‘reference procedure’, or seek a ‘preliminary ruling’ from the CLCS in order to verify the State party’s entitlement to a continental shelf beyond 200 nautical miles when the delimitation process occurs in the absence of recommendations issued by the CLCS. This article assesses the potential for a referral process bridging the relationship between the CLCS and courts and tribunals. It considers more specifically the necessity of such a mechanism and the legal challenges that are likely to arise in its establishment.
Effects of postoperative medical treatment and expectant treatment on dysmenorrhea after conservative laparoscopic surgery for deep-infiltrating endometriosis accompanied by dysmenorrhea
Authors: Zhu Qian , Ma Jue , Zhao Xiaoya , Liang Guiling , Zhai Jing , Zhang Jian 
Published: June 2020

Objective To compare the efficacy of postoperative adjuvant treatment (gonadotropin-releasing hormone agonists [GnRHas] and oral contraceptives [OCs]) and expectant treatment in preventing recurrent dysmenorrhea following conservative laparoscopic surgery for deep infiltrating endometriosis (DIE) with dysmenorrhea. Methods A prospective cohort study was conducted in Shanghai, China. In total, 147 patients with dysmenorrhea who underwent conservative laparoscopic surgery for DIE were enrolled. Following surgery, patients received either postoperative adjuvant therapy (GnRHa or OCs) for 6 months or expectant treatment according to a shared medical decision-making approach. The primary outcome was the postoperative recurrence of dysmenorrhea. The secondary outcomes included reproductive outcomes and drug-induced side effects. Results The generalized estimating equation analysis illustrated that the visual analog scale for dysmenorrhea was significantly higher in the adjuvant treatment group than in the expectant treatment group. Kaplan–Meier analysis and the log-rank test demonstrated that the cumulative recurrence rate was higher in the expectant treatment group than in the adjuvant treatment group, but no difference was noted between the two hormonal treatments. Similar cumulative 24-month clinical pregnancy rates were observed among the three groups. Conclusions Compared with expectant management, postoperative medical treatment more effectively relieved symptoms and prevented the recurrence of dysmenorrhea.
Differences Between Races in Health Information Seeking and Trust Over Time: Evidence From a Cross-Sectional, Pooled Analyses of HINTS Data
Authors: Fareed Naleef , Swoboda Christine M. , Jonnalagadda Pallavi , Walker Daniel M. , Huerta Timothy R. 
Published: June 2020

Purpose: Assessed racial disparities in health information-seeking behavior and trust of information sources from 2007 to 2017. Design: Pooled cross-sectional survey data. Setting: Health Information National Trends Survey (HINTS). Participation: Data included 6 iterations of HINTS (pooled: N = 19 496; 2007: n = 3593; 2011: n = 3959; 2013: n = 3185; Food and Drug Administration [FDA] 2015: n = 3738; 2017: n = 3285; and FDA 2017: n = 1736). Measures: Outcome variables were health information seeking, high confidence, and high trust of health information from several sources. Independent variable was race group, controlling for other sociodemographic and socioeconomic variables. Analysis: Weighted descriptive and multivariate logistic regression for the pooled sample assessed associations by race. Fully interacted models with race–survey year interactions compared differences in outcomes between years. Results: Black respondents, relative to white, had greater odds of having high confidence in their ability to attain health information, trust of health information from newspapers and magazines, radio, internet, television, government, charitable organizations, and religious organizations. Hispanic respondents, relative to white, had lower odds of seeking health information and trusting health information from doctors. They had higher odds of trusting health information from the radio, the internet, television, charitable organizations, and religious organizations. Conclusion: Disparities between races in trust of information sources remained across time. Understanding optimal information media, their reach, and credibility among racial groups could enable more targeted approaches to developing interventions. Our analytical approach minimized limitations present in the HINTS.
Sodium valproate prescription to women of childbearing age in a New Zealand inpatient psychiatric unit
Authors: Goldspink Rachel , Pumipi Toni , Dey Sangeeta , Menkes David B 
Published: June 2020

Objective: Sodium valproate’s teratogenicity has prompted increasing restriction in its use. It is still widely prescribed to women of childbearing age in New Zealand. To examine this problem, we audited the prescribing pattern of sodium valproate in a psychiatric inpatient unit in New Zealand. Method: We reviewed the clinical records of women admitted over a 2-year period (2016–2018). Results were analysed and compared with local and international guidelines. Results: Five hundred and thirty-four women of child-bearing age were admitted over the sampling period, 96 of whom (18%) were prescribed valproate on discharge. Half of these patients had diagnoses other than bipolar affective disorder, valproate’s only approved psychiatric indication in New Zealand. Pregnancy testing and contraception status were documented in a minority (29 and 10 cases, respectively). Teratogenic risk discussion was documented in only 11 cases. Conclusions: Prescription of valproate to women of childbearing age in our sample currently falls well short of best practice. Urgent action at both clinician and organisational levels is required to address this risk.