bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metallomics in deep time and the influence of ocean chemistry on the metabolic landscapes of Earth’s earliest ecosystems
Authors: Hickman-Lewis Keyron , Cavalazzi Barbara , Sorieul Stéphanie , Gautret Pascale , Foucher Frédéric , Whitehouse Martin J. , Jeon Heejin , Georgelin Thomas , Cockell Charles S. , Westall Frances 
Published: March 2020

AbstractModern biological dependency on trace elements is proposed to be a consequence of their enrichment in the habitats of early life together with Earth’s evolving physicochemical conditions; the resulting metallic biological complement is termed the metallome. Herein, we detail a protocol for describing metallomes in deep time, with applications to the earliest fossil record. Our approach extends the metallome record by more than 3 Ga and provides a novel, non-destructive method of estimating biogenicity in the absence of cellular preservation. Using microbeam particle-induced X-ray emission (µPIXE), we spatially quantify transition metals and metalloids within organic material from 3.33 billion-year-old cherts of the Barberton greenstone belt, and demonstrate that elements key to anaerobic prokaryotic molecular nanomachines, including Fe, V, Ni, As and Co, are enriched within carbonaceous material. Moreover, Mo and Zn, likely incorporated into enzymes only after the Great Oxygenation Event, are either absent or present at concentrations below the limit of detection of µPIXE, suggesting minor biological utilisation in this environmental setting. Scanning and transmission electron microscopy demonstrates that metal enrichments do not arise from accumulation in nanomineral phases and thus unambiguously reflect the primary composition of the carbonaceous material. This carbonaceous material also has δ13C between −41.3‰ and 0.03‰, dominantly −21.0‰ to −11.5‰, consistent with biological fractionation and mostly within a restricted range inconsistent with abiotic processes. Considering spatially quantified trace metal enrichments and negative δ13C fractionations together, we propose that, although lacking cellular preservation, this organic material has biological origins and, moreover, that its precursor metabolism may be estimated from the fossilised “palaeo-metallome”. Enriched Fe, V, Ni and Co, together with petrographic context, suggests that this kerogen reflects the remnants of a lithotrophic or organotrophic consortium cycling methane or nitrogen. Palaeo-metallome compositions could be used to deduce the metabolic networks of Earth’s earliest ecosystems and, potentially, as a biosignature for evaluating the origin of preserved organic materials found on Mars.
The use of circulating cell-free tumor DNA in routine diagnostics of metastatic melanoma patients
Authors: Knuever Jana , Weiss Jonathan , Persa Oana-Diana , Kreuzer Karl , Mauch Cornelia , Hallek Michael , Schlaak Max 
Published: March 2020

AbstractModern advances in technology such as next-generation sequencing and digital PCR make detection of minor circulating cell-free tumor DNA amounts in blood from cancer patients possible. Samples can be obtained minimal-invasively, tested for treatment-determining genetic alterations and are considered to reflect the genetic constitution of the whole tumor mass. Furthermore, tumor development can be determined by a time course of the quantified circulating cell-free tumor DNA. However, systematic studies which prove the clinical relevance of monitoring patients using liquid biopsies are still lacking. In this study, we collected 115 samples from 47 late stage melanoma patients over 1.5 years alongside therapy-associated clinical routine monitoring. Mutation status was confirmed by molecular analysis of primary tumor material. We can show that detectable levels of circulating cell-free tumor DNA correlate with clinical development over time. Increasing levels of circulating cell-free tumor DNA during melanoma treatment with either targeted therapy (BRAF/MEK inhibitors) or immunotherapy, during recovery time or the intervals between last treatment cycle and second-line treatment point towards clinical progression before the progression becomes obvious in imaging. Therefore, this is a further possibility to closely screen our patients for tumor progression during therapy, in therapy-free phases and in earlier stages before therapy initiation.
GPNMB is expressed in human epidermal keratinocytes but disappears in the vitiligo lesional skin
Authors: Biswas Kazal Boron , Takahashi Aya , Mizutani Yukiko , Takayama Satoru , Ishitsuka Asako , Yang Lingli , Yang Fei , Iddamalgoda Arunasiri , Katayama Ichiro , Inoue Shintaro 
Published: March 2020

AbstractGPNMB is involved in multiple cellular functions including cell adhesion, stress protection and stem cell maintenance. In skin, melanocyte-GPNMB is suggested to mediate pigmentation through melanosome formation, but details of keratinocyte-GPNMB have yet to be well understood. We confirmed the expression of GPNMB in normal human epidermal keratinocytes (NHEKs) by reducing the expression using siRNA. A higher calcium concentration of over 1.25 mM decreased the GPNMB expression. Histological staining showed that GPNMB was expressed in the basal layer of normal skins but completely absent in vitiligo skins. The normal expression of GPNMB in nevus depigmentosus skin suggested that lack of GPNMB is characteristic of vitiligo lesional skins. IFN-γ and IL-17A, two cytokines with possible causal roles in vitiligo development, inhibited GPNMB expression in vitro. Approximately 4–8% of the total GPNMB expressed on NHEKs were released possibly by ADAM 10 as a soluble form, but the process of release was not affected by the cytokines. The suppressive effect of IFN-γ on GPNMB was partially via IFN-γ/JAK2/STAT1 signaling axis. Decreased GPNMB expression in keratinocytes may affect melanocyte maintenance or survival against oxidative stress although further studies are needed. These findings indicate a new target for vitiligo treatment, focusing on the novel role of IFN-γ and IL-17 in downregulating keratinocyte-GPNMB.
Quantifying Differences in Heritability among Psoriatic Arthritis (PsA), Cutaneous Psoriasis (PsC) and Psoriasis vulgaris (PsV)
Authors: Li Quan , Chandran Vinod , Tsoi Lam , O’Rielly Darren , Nair Rajan P. , Gladman Dafna , Elder James T. , Rahman Proton 
Published: March 2020

AbstractChronic plaque psoriasis and psoriatic arthritis are multifactorial inter-related diseases with strong genetic contributions. Better elucidation of the heritability of psoriatic disease subsets is important for identifying novel genes, risk stratification and potential clinical applications. In this study, we used two mixed-effect modelling methodologies to assess the additive contribution of common single nucleotide polymorphisms from genome-wide association studies to estimate the heritability of cutaneous psoriasis, psoriasis vulgaris and psoriatic arthritis. We found that cutaneous psoriasis and psoriatic arthritis both exhibit considerable heritability, with a greater contribution coming from cutaneous psoriasis.
The COX-2/PGE2 pathway suppresses apical elimination of RasV12-transformed cells from epithelia
Authors: Sato Nanami , Yako Yuta , Maruyama Takeshi , Ishikawa Susumu , Kuromiya Keisuke , Tokuoka Suzumi M. , Kita Yoshihiro , Fujita Yasuyuki 
Published: March 2020

AbstractAt the initial stage of carcinogenesis, when RasV12-transformed cells are surrounded by normal epithelial cells, RasV12 cells are apically extruded from epithelia through cell competition with the surrounding normal cells. In this study, we demonstrate that expression of cyclooxygenase (COX)−2 is upregulated in normal cells surrounding RasV12-transformed cells. Addition of COX inhibitor or COX-2-knockout promotes apical extrusion of RasV12 cells. Furthermore, production of Prostaglandin (PG) E2, a downstream prostanoid of COX-2, is elevated in normal cells surrounding RasV12 cells, and addition of PGE2 suppresses apical extrusion of RasV12 cells. In a cell competition mouse model, expression of COX-2 is elevated in pancreatic epithelia harbouring RasV12-exressing cells, and the COX inhibitor ibuprofen promotes apical extrusion of RasV12 cells. Moreover, caerulein-induced chronic inflammation substantially suppresses apical elimination of RasV12 cells. These results indicate that intrinsically or extrinsically mediated inflammation can promote tumour initiation by diminishing cell competition between normal and transformed cells.
Urine metallomics signature as an indicator of pancreatic cancer
Authors: Schilling Kathrin , Larner Fiona , Saad Amina , Roberts Rhiannon , Kocher Hemant M , Blyuss Oleg , Halliday Alex N , Crnogorac-Jurcevic Tatjana 
Published: March 2020

Abstract
Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest types of cancer. Its high mortality rate is attributed largely to the difficulty of early diagnosis. Analysis of urine is an excellent non-invasive approach to trace changes in biochemical reactions due to cancer development. Here we show remarkable differences in concentration of several essential metals: significantly lower levels of urinary calcium and magnesium and increased levels of copper and zinc in PDAC when compared to healthy controls, and demonstrate that a combined analysis of these essential metals are accurate indicators (sensitivity = 99.5%) for metal dyshomeostasis in PDAC. In addition, natural stable zinc isotope composition (δ66/64Zn) in urine reveals the preferential excretion of isotopically light zinc in PDAC (δ66/64Znmedian = −0.15‰) compared to healthy controls (δ66/64Znmedian = +0.02‰), likely supporting the dysregulation of metalloproteins. These findings demonstrate for the first time that metallomics is a promising approach for discovery of biomarkers for detection of patients with PDAC, completely non-invasively, using urine samples.
Autophagy attenuates high glucose-induced oxidative injury to lens epithelial cells
Authors: Liu Xiaomin , Zhao Xiaowen , Cheng Rong , Huang Yusen 
Published: March 2020

Abstract
Purpose: Autophagic dysfunction and abnormal oxidative stress are associated with cataract. The purpose of the present study was to investigate the changes of cellular autophagy and oxidative stress and their association in lens epithelial cells (LECs) upon exposure to high glucose.
Methods: Autophagy and oxidative stress-related changes were detected in streptozotocin-induced Type 1 diabetic mice and normal mouse LECs incubated in high glucose conditions. Rapamycin at a concentration of 100 nm/l or 50 μM chloroquine was combined for analysis of the relationship between autophagy and oxidative stress. The morphology of LECs during autophagy was observed by transmission electron microscopy. The expressions of autophagy markers (LC3B and p62) were identified, as well as the key factors of oxidative stress (SOD2 and CAT) and mitochondrial reactive oxygen species (ROS) generation.
Results: Transmission electron microscopy indicated an altered autophagy activity in diabetic mouse lens tissues with larger autophagosomes and multiple mitochondria. Regarding the expressions, LC3B was elevated, p62 was decreased first and then increased, and SOD2 and CAT were increased before a decrease during 4 months of follow-up in diabetic mice and 72 h of culture under high glucose for mouse LECs. Furthermore, rapamycin promoted the expressions of autophagy markers but alleviated those of oxidative stress markers, whereas chloroquine antagonized autophagy but enhanced oxidative stress by elevating ROS generation in LECs exposed to high glucose.
Conclusions: The changes in autophagy and oxidative stress were fluctuating in the mouse LECs under constant high glucose conditions. Autophagy might attenuate high glucose-induced oxidative injury to LECs.
LHPP suppresses proliferation, migration, and invasion and promotes apoptosis in pancreatic cancer
Authors: Wu Fahong , Chen Yanling , Zhu Jinhai 
Published: March 2020

Abstract
Pancreatic cancer (PaCa) is a common malignant tumor of the digestive system with poor prognosis and no ideal treatment for inoperable patients, which is partly due to delayed diagnoses. It is recently reported that the protein histidine phosphatase LHPP is a tumor suppressor in hepatocellular carcinoma, cervical cancer, and bladder cancer. So far, there is no study on the expression level of LHPP in PaCa, and its mechanism of action on tumors is unclear. In this experiment, LHPP expression was lower in cancer tissues than that in normal pancreatic tissue, and clinicopathological results showed that LHPP expression was correlated with the degree of differentiation and lymphatic metastasis of pancreatic carcinoma. The biological characteristics of LHPP in PaCa cells were examined by the cell counting kit-8 assay, transwell assay, and monoclonal formation test. The inhibitory mechanism of LHPP in PaCa cells was determined using Western blotting and flow cytometry. The results showed that LHPP restrained PaCa cell proliferation, migration, and invasion. Increased LHPP expression promoted the apoptosis of PaCa cells through higher activation of cleaved-PARP and cleaved-Casp3 and lower activation of cIAP1. Importantly, the increase in LHPP enhanced PTEN expression and decreased the phosphorylated AKT level. Moreover, LHPP-induced apoptosis was diminished by SC79 (AKT activator) in PaCa cells. In conclusion, LHPP blocks proliferation, migration, and invasion and enhances apoptosis in PaCa cells through the PTEN/AKT signaling pathway.
Hepatocyte growth factor protects PC12 cells against OGD/R-induced injury by reducing iron
Authors: Li Siyue , Qian Zhong-Ming , Xu Gaojing , Zheng Jie , Wu Yi 
Published: March 2020

Abstract
In the light of hepatocyte growth factor (HGF) the inhibiting role on the expression of hepcidin, we hypothesized that HGF might be able to reduce cell and tissue iron by increasing ferroportin 1 (Fpn1) content and Fpn1-mediated iron release from cells and tissues. The hypothesized ability of HGF to reduce iron might be one of the mechanisms associated with its neuroprotective action under the conditions of ischemia/reperfusion (I/R). Here, we investigated the effects of HGF on the expression of hepcidin as well as transferrin receptor 1 (TfR1), divalent metal transporter 1 (DMT1), Fpn1, ferritin and iron regulatory proteins (IRPs) in oxygen-glucose deprivation and reoxygenation (OGD/R)-treated PC12 cells by real-time PCR and Western blot analysis. We demonstrated that HGF could completely reverse the OGD/R-induced reduction in Fpn1 and IRP1 expression and increase in ferritin light chain protein and hepcidin mRNA levels in PC12 cells. It was concluded that HGF protects PC12 cells against OGD/R-induced injury mainly by reducing cell iron contents via the up-regulation of Fpn1 and increased Fpn1-mediated iron export from cells. Our findings suggested that HGF may also be able to ameliorate OGD/R or I/R-induced overloading of brain iron by promoting Fpn1 expression.
Age-Related Changes in Speech and Voice: Spectral and Cepstral Measures
Authors: Taylor Sammi , Dromey Christopher , Nissen Shawn L. , Tanner Kristine , Eggett Dennis , Corbin-Lewis Kim 
Published: March 2020

Purpose
This study examined differences in selected acoustic measures of speech and voice according to age and sex and across families.

Method
Participants included 169 individuals, 79 men and 90 women, from 18 families, ranging in age from 17 to 87 years. Participants reported no history of articulation disorders, stroke or active neurologic disease, or severe-to-profound hearing loss. They read aloud two passages to facilitate examination of the following speech and voice acoustic parameters: fricative spectral moments (center of gravity, standard deviation, skewness, and kurtosis), the proportion of time spent speaking, mean speaking fundamental frequency, semitone standard deviation (STSD), and cepstral peak prominence smoothed.

Results
The results indicated a significant age effect for fricative spectral center of gravity, spectral skewness, and speaking STSD. There was a significant sex effect for spectral center of gravity, spectral kurtosis, and mean fundamental frequency. Familial relationship was significant for spectral skewness, STSD, and cepstral peak prominence smoothed.

Conclusions
These findings revealed that certain speech and voice features change with age and some change differently for men and women. Additionally, speakers from the same family units may demonstrate similar patterns for prosody, voicing, and articulatory behavior. The results also demonstrated normal differences in speech and voice variation across age, sex, and family unit. Understanding patterns and differences across these demographic variables in healthy speakers is important to distinguishing more confidently between normal and disordered speech and voice patterns clinically.
H II regions and high-mass starless clump candidates
Authors: Zhang S. , Zavagno A. , Yuan J. , Liu H. , Figueira M. , Russeil D. , Schuller F. , Marsh K. A. , Wu Y. 
Published: March 2020

Context. The role of ionization feedback on high-mass (>8 M⊙) star formation is still highly debated. Questions remain concerning the presence of nearby H II regions changes the properties of early high-mass star formation and whether H II regions promote or inhibit the formation of high-mass stars.
Aims. To characterize the role of H II regions on the formation of high-mass stars, we study the properties of a sample of candidates high-mass starless clumps (HMSCs), of which about 90% have masses larger than 100 M⊙. These high-mass objects probably represent the earliest stages of high-mass star formation; we search if (and how) their properties are modified by the presence of an H II region.
Methods. We took advantage of the recently published catalog of HMSC candidates. By cross matching the HMSCs and H II regions, we classified HMSCs into three categories: (1) the HMSCs associated with H II regions both in the position in the projected plane of the sky and in velocity; (2) HMSCs associated in the plane of the sky, but not in velocity; and (3) HMSCs far away from any H II regions in the projected sky plane. We carried out comparisons between associated and nonassociated HMSCs based on statistical analyses of multiwavelength data from infrared to radio.
Results. We show that there are systematic differences of the properties of HMSCs in different environments. Statistical analyses suggest that HMSCs associated with H II regions are warmer, more luminous, more centrally-peaked and turbulent. We also clearly show, for the first time, that the ratio of bolometric luminosity to envelope mass of HMSCs (L∕M) could not be a reliable evolutionary probe for early massive star formation due to the external heating effects of the H II regions.
Conclusions. We show HMSCs associated with H II regions present statistically significant differences from HMSCs far away from H II regions, especially for dust temperature and L∕M. More centrally peaked and turbulent properties of HMSCs associated with H II regions may promote the formation of high-mass stars by limiting fragmentation. High-resolution interferometric surveys toward HMSCs are crucial to reveal how H II regions impact the star formation process inside HMSCs.
CO-driven activity constrains the origin of comets
Authors: Fulle M. , Blum J. , Rotundi A. 
Published: March 2020

Context.An open question in the study of comets is the so-called cohesion bottleneck, that is, how dust particles detach from the nucleus.Aims.We test whether the CO pressure buildup inside the pebbles of which cometary nuclei consist can overcome this cohesion bottleneck.Methods.A recently developed pebble-diffusion model was applied here to comet C/2017K2 PANSTARRS, assuming a CO-driven activity.Results.(i) The CO-gas pressure inside the pebbles erodes the nucleus into the observed dust, which is composed of refractories, H2O ice and CO2ice. (ii) The CO-driven activity onset occurs up to heliocentric distances of 85 au, depending on the spin orientation of the comet nucleus. (iii) The activity onset observed at ≈26 au suggests a low obliquity of the nucleus spin axis with activity in a polar summer. (iv) At 14 au, the smallest size of the ejected dust is ≈0.1 mm, consistent with observations. (v) The observed dust-loss rate of ≈200 kg s−1implies a fallout ≥30%, a nucleus surface active area ≥10 km2, a CO-gas loss rate ≥10 kg s−1, and a dust-to-gas ratio ≤20. (vi) The CO-driven activity never stops if the average refractory-to-all-ices mass ratio in the nucleus is ≤4.5 for a nucleus all-ices-to-CO mass ratio ≈4, as observed in comets Hale–Bopp and Hyakutake. These results make comet C/2017K2 similar to the Rosetta target comet 67P/Churyumov–Gerasimenko. (vii) The erosion lifetime of cometary planetesimals is a factor 103shorter than the timescale of catastrophic collisions. This means that the comets we observe today cannot be products of catastrophic collisions.
Antikoagulation bei über 80-jährigen Patienten mit Vorhofflimmern
Authors: Zeymer Uwe , Zahn Ralf 
Published: March 2020

ZUSAMMENFASSUNGDie Zahl von Patienten über 80-Jahre mit Vorhofflimmern wird durch den demografischen Wandel über die nächsten Jahre ständig zunehmen. Da all diese Patienten einen CHADS-VASc-Score von > 2 haben, empfehlen die derzeitigen Leitlinien eine orale Antikoagulation. Auch wegen des erhöhten Schlaganfall-Risikos bei über 80-Jährigen führt die orale Antikoagulation mit Vitamin-K-Antagonisten zu einer signifikanten Verringerung der Rate ischämischer Schlaganfälle. In den randomisierten Zulassungsstudien führten die NOAKs im direkten Vergleich zu den Vitamin-K-Antagonisten zu einer Verringerung der Gesamtschlaganfallrate, im Wesentlichen bedingt durch eine drastische Reduktion der hämorrhagischen Schlaganfälle. Dieser Effekt war bei den über 75-jährigen Patienten sogar ausgeprägter als bei den jüngeren Patienten. Probleme bei den > 80-Jährigen stellen die Adhärenz zur oralen Antikoagulation, Verschlechterungen der Nierenfunktion und eine häufig beobachtete Polypharmazie sowie das damit verbundene Risiko für Blutungskomplikationen dar.
Transoral incisionless fundoplication with an ultrasonic surgical endostapler for the treatment of gastroesophageal reflux disease: 12-month outcomes
Authors: Testoni Pier Alberto , Testoni Sabrina , Mazzoleni Giorgia , Pantaleo Giuseppe , Cilona Maria Bernadette , Distefano Giovanni , Fanti Lorella , Antonelli Mario , Passaretti Sandro 
Published: March 2020

Background Transoral incisionless fundoplication (TIF) with the Medigus ultrasonic surgical endostapler (MUSE) is a new intervention for the treatment of the gastroesophageal reflux disease (GERD). The aim of this study was to assess the 12-month clinical, functional, and endoscopic effects of TIF by MUSE.
Methods Patients undergoing MUSE completed the GERD-Health Related Quality of Life (GERD-HRQL) and Reflux Symptom Index (RSI) questionnaires, and underwent endoscopy, esophageal 24-hour pH-impedance recording, and high resolution manometry (HRM) before the TIF procedure and 12 months later, or after 6 months for HRM.
Results Among the 37 patients treated, esophageal intubation was not possible in one and esophageal perforation occurred in another. Clinical and endoscopic follow-up at 12 months was completed in 20 patients, with significant improvements in GERD-HRQL, RSI, heartburn, regurgitation scores, and proton pump inhibitor (PPI) consumption observed. One patient required surgery for persisting symptoms. Functional follow-up was possible in 13 patients and showed no significant improvements in the analyzed parameters.
Conclusions TIF with MUSE significantly improved symptoms at 1-year follow-up, allowing the consumption of PPIs to be stopped or halved in 90 % of patients.