bluuebunny/crossref_metadata_2025_split huggingface dataset:
IRE1α and IGF signaling predict resistance to an endoplasmic reticulum stress-inducing drug in glioblastoma cells
Authors: Rodvold Jeffrey J. , Xian Su , Nussbacher Julia , Tsui Brian , Cameron Waller T. , Searles Stephen C. , Lew Alyssa , Jiang Pengfei , Babic Ivan , Nomura Natsuko , Lin Jonathan H. , Kesari Santosh , Carter Hannah , Zanetti Maurizio 
Published: May 2020

AbstractTo date current therapies of glioblastoma multiforme (GBM) are largely ineffective. The induction of apoptosis by an unresolvable unfolded protein response (UPR) represents a potential new therapeutic strategy. Here we tested 12ADT, a sarcoendoplasmic reticulum Ca2+ ATPase (SERCA) inhibitor, on a panel of unselected patient-derived neurosphere-forming cells and found that GBM cells can be distinguished into “responder” and “non-responder”. By RNASeq analysis we found that the non-responder phenotype is significantly linked with the expression of UPR genes, and in particular ERN1 (IRE1) and ATF4. We also identified two additional genes selectively overexpressed among non-responders, IGFBP3 and IGFBP5. CRISPR-mediated deletion of the ERN1, IGFBP3, IGFBP5 signature genes in the U251 human GBM cell line increased responsiveness to 12ADT. Remarkably, >65% of GBM cases in The Cancer Genome Atlas express the non-responder (ERN1, IGFBP3, IGFBP5) gene signature. Thus, elevated levels of IRE1α and IGFBPs predict a poor response to drugs inducing unresolvable UPR and possibly other forms of chemotherapy helping in a better stratification GBM patients.
The Boiling Phenomena and their Proper Identification and Discrimination Methodology
Authors: Pati A. R. , Swain B. , Mohapatra S. S. 
Published: May 2020

AbstractThe proper identification of the existence of the boiling phenomena in a process from the trend of the Nukiyama pool-boiling curve (Q versus ∆T) is not appropriate as it does not always reveal right information. All the heating and cooling around the boiling point mimic the boiling behavior; however, these are not always actually a part of the boiling process. Therefore, the proper identification and discrimination among boiling methodologies need to be revealed as the information on the discussed issues are not available in the open literature. Hence, an attempt has been made to develop a condition describing the existence of boiling behavior in heating or quenching process and protocol to identify various boiling regimes. In the current work, the developed conditions (1/ St) are validated with various type of boiling processes and the protocol (i.e. based on the slope of h versus ∆T curve rather than boiling curve) is also valid for the identification of proper boiling regime.
Fragrant rice performances in response to continuous zero-tillage in machine-transplanted double-cropped rice system
Authors: Du Bin , He Longxin , Lai Rifang , Luo Haowen , Zhang Tantan , Tang Xiangru 
Published: May 2020

AbstractZero-tillage is one of conservation tillage techniques. In order to investigate the effects of continuous zero-tillage on yield formation and grain 2-acetyl-1-pyrroline (2-AP, key component of fragrant rice aroma) content of fragrant rice, present study was conducted with a six-season field experiment from 2017 to 2019. The conventional tillage (twice puddling with rotary cultivator before transplanting) was set as control (CK) and zero-tillage was set as treatment (ZT). At the first year after applying zero-tillage, yield loss was observed in the ZT treatment which was attributed to the lower effective panicle number per area and grain number per panicle. However, from late season in 2018 to late season in 2019, significant higher grain yield was recorded in ZT than CK. ZT increased the net photosynthetic rate and chlorophyll content (SPAD value) by 6.81–20.77% and 7.23–23.80% in the last three cropping seasons compared with CK. Higher nitrogen, potassium and phosphorus accumulations in plant tissues were also recorded in ZT than CK from late season in 2018 to late season in 2019. Other hand, higher grain 2-AP content was recorded in ZT than CT in the whole six cropping seasons which might be related to the grain proline content. Furthermore, compared with CK, ZT significantly increased the soil organic matter content and the number of bacteria, fungi and actinomycetes in the last three cropping seasons. In conclusion, continuous zero-tillage could improve soil and increase the photosynthesis and nutrient accumulation and finally achieve the improvement of fragrant rice yield.
Combinatorial approach of in silico and in vitro evaluation of MLH1 variant associated with Lynch syndrome like metastatic colorectal cancer
Authors: Saleem Komal , Zaib Tahir , Ji Wei , Zhang Chunhui , Qin Qian , Wang Yusi , Xu Lidan , Yu Hanfei , Zhu Siqi , Dong Kexian , Si Shuhan , Jia Xueyuan , Wu Jie , Fu Songbin , Sun Wenjing 
Published: May 2020

Abstract
Colorectal cancer (CRC) is the third most developing cancer worldwide and Lynch syndrome (LS) accounts for 3–4% of CRC. Genetic alteration in any of DNA mismatch repair (MMR) gene is the major cause of LS that disrupt the normal upstream and downstream MMR events. Germline mutation of MLH1 in heterozygous state have an increased risk for CRC. Defective MMR pathway mostly results in microsatellite instability (MSI) that occurs in high percentage of CRC associated tumors. Here, we reported a patient with LS like metastatic CRC (mCRC) associated with other related cancers. Whole exome sequencing (WES) of the proband was performed to identify potential causative gene. Genetic screening validated by Sanger sequencing identified a heterozygous missense mutation in exon 12 of MLH1 (c.1151T&gt;A, p.V384D). The clinical significance of identified variant was elucidated on the basis of clinicopathological data, computational predictions and various in vitro functional analysis. In silico predictions classified the variant to be deleterious and evolutionary conserved. In vitro functional studies revealed a significant decrease in protein expression because of stability defect leading to loss of MMR activity. Mutant residue found in MutL transducer domain of MLH1 that localized in the nucleus but translocation was not found to be significantly disturbed. In conclusion, our study give insight into reliability of combinatorial prediction approach of in silico and in vitro expression analysis. Hence, we highlighted the pathogenic correlation of MLH1 variant with LS associated CRC as well as help in earlier diagnosis and surveillance for improved management and genetic counselling.
LncRNA SNHG12 contributes proliferation, invasion and epithelial–mesenchymal transition of pancreatic cancer cells by absorbing miRNA-320b
Authors: Cao Wei , Zhou Guoxiong 
Published: May 2020

Abstract
Pancreatic cancer is a kind of malignant carcinoma with high mortality, which is devoid of early diagnostic biomarker and effective therapeutic methods. Recently, long non-coding RNAs (lncRNAs) have been reported as a crucial role in regulating the development of various kinds of tumors. Here, we found lncRNA small nuclear RNA host gene 12 (SNHG12) is highly expressed in pancreatic cancer tissues and cell lines through qRT-PCR, which suggested that SNHG12 possibly accelerates the progression of pancreatic cancer. Further study revealed that SNHG12 promoted cancer cells growth and invasion via absorbing miR-320b. Flow cytometry and transwell chamber assay were utilized to verify the promoting effects on proliferation and invasion that SNHG12 acts in pancreatic cancer cells. Evidence that SNHG12 increased cell invasive ability through up-regulated EMT process was lately obtained by Western blotting assay. Consequently, we extrapolated that SNHG12/miR-320b could be invoked as a promising early diagnostic hallmark and therapeutic strategy for pancreatic cancer.
Comprehensive analysis of the value of RAB family genes in prognosis of breast invasive carcinoma
Authors: Lin Shitong , Cao Canhui , Meng Yifan , Wu Ping , Gao Peipei , Zhi Wenhua , Peng Ting , Wu Peng , Gui Lingli 
Published: May 2020

Abstract
Purpose: Several RAB family genes have been studied extensively and proven to play pivotal roles in the occurrence and development of certain cancers. Here, we explored commonly expressed RAB family genes in humans and their prognostic significance using bioinformatics, and then identified potential biomarkers of breast invasive carcinoma (BRCA). Materials and methods: The prognostic values (overall survival) of RAB family genes in BRCA were obtained using Gene Expression Profiling Interactive Analysis (GEPIA). The expression patterns of RAB family genes and their relationships with clinicopathological parameters in BRCA were measured using the ONCOMINE and UALCAN databases, respectively. Genetic mutations and survival analysis were investigated using the cBio Cancer Genomics Portal (c-BioPortal). Interacting genes of potential biomarkers were identified using STRING, and functional enrichment analyses were performed using FunRich v3.1.3. Results: In total, 64 RAB genes were identified and analyzed in our study. Results showed that RAB1B, RAB2A, and RAB18 were up-regulated and significantly associated with poor overall survival in BRCA. Furthermore, their higher expression was positively correlated with clinicopathological parameters (e.g. cancer stage and nodal metastasis status). DNA copy number amplifications and mRNA up-regulation were the main genetic mutations, and the altered group showed significantly poorer overall survival compared with the unaltered group. Functional enrichment analysis of RAB1B, RAB2A, and RAB18 indicated they were closely involved in GTPase activity. Conclusions:RAB1B, RAB2A, and RAB18 were up-regulated and significantly correlated with poor prognosis in BRCA. Thus, they could be applied as novel biomarkers of BRCA in future studies.
The HR 1614 moving group is not a dissolving cluster
Authors: Kushniruk Iryna , Bensby Thomas , Feltzing Sofia , Sahlholdt Christian L. , Feuillet Diane , Casagrande Luca 
Published: May 2020

Context. The HR 1614 is an overdensity in velocity space and has for a long time been known as an old (∼2 Gyr) and metal-rich ([Fe/H] ≈ +0.2) nearby moving group that has a dissolving open cluster origin. The existence of such old and metal-rich groups in the solar vicinity is quite unexpected since the vast majority of nearby moving groups are known to be young.
Aims. In the light of new and significantly larger data sets than ever before (astrometric, photometric, and spectroscopic), we aim to re-investigate the properties and origin of the HR 1614 moving group. If the HR 1614 overdensity is a dissolving cluster, its stars should represent a single-age and single-elemental abundance population.
Methods. To identify and characterise the HR 1614 moving group we use astrometric data from Gaia DR2; distances, extinction, and reddening corrections from the StarHorse code; elemental abundances from the GALAH and APOGEE spectroscopic surveys; and photometric metallicities from the SkyMapper survey. Bayesian ages were estimated for the SkyMapper stars. Since the Hercules stream is the closest kinematical structure to the HR 1614 moving group in velocity space and as its origin is believed to be well-understood, we use the Hercules stream for comparison purposes. Stars that are likely to be members of the two groups were selected based on their space velocities.
Results. The HR 1614 moving group is located mainly at negative U velocities, does not form an arch of constant energy in the U − V space, and is tilted in V. We find that the HR 1614 overdensity is not chemically homogeneous, but that its stars exist at a wide range of metallicities, ages, and elemental abundance ratios. They are essentially similar to what is observed in the Galactic thin and thick discs, a younger population (around 3 Gyr) that is metal-rich (−0.2  ≤  [Fe/H]  ≤  0.4) and alpha-poor. These findings are very similar to what is seen for the Hercules stream, which is believed to have a dynamical origin and consists of regular stars from the Galactic discs.
Conclusions. The HR 1614 overdensity has a wide spread in metallicity, [Mg/Fe], and age distributions resembling the general properties of the Galactic disc. It should therefore not be considered a dissolving open cluster, or an accreted population. Based on the kinematic and chemical properties of the HR 1614 overdensity we suggest that it has a complex origin that could be explained by combining several different mechanisms such as resonances with the Galactic bar and spiral structure, phase mixing of dissolving spiral structure, and phase mixing due to an external perturbation.
Galactic halo size in the light of recent AMS-02 data
Authors: Weinrich N. , Boudaud M. , Derome L. , Génolini Y. , Lavalle J. , Maurin D. , Salati P. , Serpico P. , Weymann-Despres G. 
Published: May 2020

Context.The vertical diffusive halo size of the Galaxy,L, is a key parameter for dark matter indirect searches. It can be better determined thanks to recent AMS-02 data.Aims.We set constraints onLfrom Be/B and10Be/Be data, and we performed a consistency check with positron data. We detail the dependence of Be/B and10Be/Be onLand forecast on which energy range better data would be helpful for futureLimprovements.Methods.We usedUSINE V3.5for the propagation of nuclei, and e+were calculated with the pinching method.Results.The current AMS-02 Be/B (∼3% precision) and ACE-CRIS10Be/Be (∼10% precision) data bring similar and consistent constraints onL. The AMS-02 Be/B data alone constrainL= 5−2+3kpc at a 68% confidence level (spanning different benchmark transport configurations), a range for which most models do not overproduce positrons. Future experiments need to deliver percent-level accuracy on10Be/9Be anywhere below 10 GV to further constrainL.Conclusions.Forthcoming AMS-02, HELIX, and PAMELA10Be/9Be results will further test and possibly tighten the limits derived here. Elemental ratios involving radioactive species with different lifetimes (e.g. Al/Mg and Cl/Ar) are also awaited to provide complementary and robuster constraints.
Semi-annual, annual and Universal Time variations in the magnetosphere and in geomagnetic activity: 1. Geomagnetic data
Authors: Lockwood Mike , Owens Mathew J. , Barnard Luke A. , Haines Carl , Scott Chris J. , McWilliams Kathryn A. , Coxon John C. 
Published: May 2020

We study the semi-annual variation in geomagnetic activity, as detected in the geomagnetic indices am, aaH, AL, Dst and the four aσ indices derived for 6-hour MLT sectors (around noon, dawn, dusk and midnight). For each we compare the amplitude of the semi-annual variation, as a fraction of the overall mean, to that of the corresponding variation in power input to the magnetosphere, Pα, estimated from interplanetary observations. We demonstrate that the semi-annual variation is amplified in the geomagnetic data compared to that in Pα, by a factor that is different for each index. The largest amplification is for the Dst index (factor ~ 10) and the smallest is for the aσ index for the noon MLT sector (aσ-noon, factor ≈ 1.1). By sorting the data by the prevailing polarity of the Y-component (dawn-dusk) of the Interplanetary Magnetic Field (IMF) in the Geocentric Solar Equatorial (GSEQ) reference frame, we demonstrate that the Russell-McPherron (R-M) effect, in which a small southward IMF component in GSEQ is converted into geoeffective field by Earth’s dipole tilt, is a key factor for the semi-annual variations in both Pα and geomagnetic indices. However, the variability in the southward component in the IMF in the GSEQ frame causes more variability in power input to the magnetosphere Pα than does the R-M effect, by a factor of more than two. We show that for increasingly large geomagnetic disturbances, Pα delivered by events of large southward field in GSEQ (known to often be associated with coronal mass ejections) becomes the dominant driver and the R-M effect declines in importance and often acts to reduce geoeffectiveness for the most southward IMF in GSEQ: the semi-annual variation in large storms therefore suggests either preconditioning of the magnetosphere by average conditions or an additional effect at the equinoxes. We confirm that the very large R-M effect in the Dst index is because of a large effect at small and moderate activity levels and not in large storms. We discuss the implications of the observed “equinoctial” time-of-year (F) – Universal Time (UT) pattern of geomagnetic response, the waveform and phase of the semi-annual variations, the differences between the responses at the June and December solstices and the ratio of the amplitudes of the March and September equinox peaks. We also confirm that the UT variation in geomagnetic activity is a genuine global response. Later papers will analyse the origins and implications of the effects described.
Barrieren für Gespräche über Tod und Sterben in der Medizin
Authors: Seifart Carola , Nagelschmidt Katharina , von Blanckenburg Pia 
Published: May 2020

ZusammenfassungFür viele Menschen sind Tod und Sterben etwas Schmerzliches (in vielerlei Hinsicht), dessen Vorstellung tiefgründige, starke Ängste berührt oder auslöst. Häufig wird versucht, das Thema zu vermeiden und von sich weg zu schieben. In der Medizin aber lässt sich das Thema nicht aussparen – und es gibt gute Gründe, gerade darüber zu sprechen.
Visualisierung von intraokularen Fremdkörpern im Ziliarkörperbereich mittels infraroter Transillumination (Pilotstudie)
Authors: Kogan Mykhailo , Zadorozhnyy Oleg , Korol Andrii , Petretskaya Oksana , Krasnovid Tatiana , Pasyechnikova Nataliya 
Published: May 2020

Zusammenfassung
Hintergrund Trotz der Verbesserung der Diagnosetechnologien bleibt die Detektion von intraokularen Fremdkörpern (IFK), die sich in der Projektion des Ziliarkörpers befinden, eines der aktuellen Probleme der Augentraumatologie.
Ziel Untersuchung der möglichen Visualisierung intraokularer Fremdkörper (IFK) in der Projektion des Ziliarkörpers mithilfe der infrarоten transpalpebralen Transillumination (IRTT).
Materialien und Methoden Analyse von 10 Personen (10 Augen) mit einer penetrierenden Augenwunde und nachgewiesenem IFK. In allen Fällen erfolgten Röntgendiagnostik, Ultraschalluntersuchung des Auges und IRTT.
Ergebnisse Bei allen Patienten wurden Schatten von den Strukturen des Ziliarkörpers (Pars plana, Pars plicata) auf der Sklera mittels IRTT und Schatten von IFK visualisiert.
Schlussfolgerung Die Technik der IRTT bei Patienten mit penetrierenden Augenverletzungen ermöglicht die nicht invasive Visualisierung von IFK in der Projektion des Ziliarkörpers und die Identifizierung ihrer Lokalisation.
Tränenfilmosmolarität gesunder Probanden: Vergleichbarkeit zweier Osmometer
Authors: König Susanna , Priglinger Siegfried , Schaumberger Markus , Messmer Elisabeth M. 
Published: May 2020

Zusammenfassung
Hintergrund Die Hyperosmolarität des Tränenfilms gilt als bedeutendes klinisches Zeichen des trockenen Auges und als wichtigster singulärer diagnostischer Parameter. Neben dem seit einigen Jahren verfügbaren Ocusense TearLab-Osmometer (TearLab Corp, San Diego, CA) ist seit Kurzem auch das I-Pen-Osmometer (I-MED Pharma Inc., Dollard-des-Ormeaux, Quebec, Kanada) verfügbar. Das Ziel unserer Studie war die Vergleichbarkeit der mittels TearLab- und I-Pen-Osmometer erhobenen Tränenfilmosmolarität bei gesunden Probanden zu untersuchen.
Material und Methoden 51 gesunde Probanden (mittleres Alter 40,6 Jahre, Altersspanne 17 – 63 Jahre, 66,7% weiblich) ohne Beschwerden und Zeichen eines trockenen Auges (Ocular Surface Disease Index < 13, Tränenfilmaufrisszeit > 7 s, unauffälliger Schirmer-Test > 10 mm/5 min) wurden eingeschlossen. Die Tränenfilmosmolarität wurde im Tränenfilmmeniskus (TearLab) und an der subtarsalen Bindehaut (I-Pen) mit einem Zeitintervall von 30 min erhoben. Die Reihenfolge der beiden Osmolaritätsuntersuchungen erfolgte im alternierenden Wechsel. Die statistische Analyse erfolgte mittels Wilcoxon- und Spearman-Tests.
Ergebnisse Die mittlere TearLab-Osmolarität war 295,1 mosmol/l (rechtes Auge), 294,0 mosmol/l (linkes Auge) sowie 294,6 mosmol/l (bilateral) mit einer Variationsbreite von 268 – 394 mosmol/l. Mittels I-Pen-Osmometer erhobene mittlere Osmolaritätswerte lagen bei 301,6 mosmol/l (rechtes Auge), 302,5 mosmol/l (linkes Auge) und 302,1 mosmol/l bilateral mit einer Variationsbreite von 276 – 394 mosmol/l. Es zeigte sich ein signifikanter Unterschied in den erhobenen Tränenfilmosmolaritäten mit den beiden Techniken für beide Augen einzeln (p < 0,02) und beim Mittelwert beider Augen (p < 0,001). Die Messungen mit beiden Geräten korrelierten nicht signifikant (r = 0,27 rechts und r = 0,08 links). Bei einem – wie von TearLab vorgeschlagenen – Grenzwert von 308 mosmol/l lagen 98,0% der TearLab-Werte, aber nur 68,6% der I-Pen-Werte im Normbereich.
Schlussfolgerung Die mittels I-Pen gemessenen Osmolaritätswerte zeigten sich signifikant höher im Vergleich zu den mit TearLab erhobenen Messwerten. Für diesen Unterschied verantwortlich könnte u. a. die Lokalisation der Messung an der subtarsalen Konjunktiva mit dem I-Pen im Vergleich zur Messung im Tränenfilmmeniskus mit dem TearLab sein. Es könnte daher notwendig sein, den Grenzwert zur Unterscheidung pathologischer Werte von physiologischen Werten bei Messungen der Tränenfilmosmolarität mit dem I-Pen-Osmometer zu ändern. Weiterführende Untersuchungen an einer größeren Kohorte von Normalprobanden sowie bei Patienten mit trockenem Auge sind hierfür notwendig.
Messung der Dichte der Langerhans-Zellen als Verlaufsparameter bei Patienten mit Keratoconjunctivitis sicca unter topischer antiinflammatorischer Therapie mit Ciclosporin A 0,05% Augentropfen
Authors: Schneider Eva , Paulsen Friedrich , Jacobi Christina 
Published: May 2020

Zusammenfassung
Hintergrund Die Keratoconjunctivitis sicca ist eine der häufigsten okulären Erkrankungen mit entscheidender Beeinträchtigung der Lebensqualität. Die Erkrankung wird begleitet von okulären Symptomen, Tränenfilminstabilität, Hyperosmolarität und einer Entzündung der Augenoberfläche mit neurosensorischen Störungen. Noch nicht eindeutig geklärt ist, inwieweit die Dichte der Langerhans-Zellen in der Hornhaut zur Objektivierung der Entzündungsreaktion herangezogen werden kann.
Patienten und Methoden 47 Patienten (13 Männer und 34 Frauen) im Alter von 21 bis 85 Jahren mit moderater bis schwerer Keratoconjunctivitis sicca (DEWS-Schweregrad 2 – 3) konnten in dieser prospektiven klinischen Studie ausgewertet werden. Die Patienten erhielten über 3 Monate eine topische antiinflammatorische Therapie mit Ciclosporin A 0,05% Augentropfen 2 × täglich. Folgende Parameter wurden untersucht: OSDI-Score, Tränenfilmaufreißzeit (TBUT), Schirmer-Test mit Anästhesie, lidkantenparallele konjunktivale Falten (LIPCOF), Dichte der Langerhans-Zellen in der zentralen Hornhaut gemessen mittels konfokaler In-vivo-Mikroskopie mit HRT II und RCM, Visus, Tränenfilmosmolarität, Meibom-Drüsen-Dysfunktion (MDD).
Ergebnisse Nach dem Behandlungszeitraum zeigte sich eine signifikante Reduktion der Langerhans-Zelldichte im Bereich der zentralen Hornhaut (p ≤ 0,001**), eine Zunahme der TBUT (p ≤ 0,001**) sowie eine Abnahme von Tränenfilmosmolarität (p ≤ 0,05*) und OSDI-Score (p ≤ 0,001**). Visus, MDD und Schirmer-Test änderten sich nicht signifikant.
Schlussfolgerungen Unsere Untersuchungsergebnisse zeigen, dass eine antiinflammatorische topische Ciclosporin-A-Therapie bei Patienten mit moderater bis schwerer Keratoconjunctivitis sicca effektiv die Entzündungsmechanismen der Augenoberfläche und des Tränenfilms reduziert und die Lebensqualität der betroffenen Patienten verbessert. Die Messung der Dichte der Langerhans-Zellen im Zentrum der Hornhaut ist mittels konfokaler In-vivo-Mikroskopie möglich und als objektives Testverfahren im Therapiemonitoring sinnvoll.