bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrative and comparative genomic analyses identify clinically relevant pulmonary carcinoid groups and unveil the supra-carcinoids
Authors: Alcala N. , Leblay N. , Gabriel A. A. G. , Mangiante L. , Hervas D. , Giffon T. , Sertier A. S. , Ferrari A. , Derks J. , Ghantous A. , Delhomme T. M. , Chabrier A. , Cuenin C. , Abedi-Ardekani B. , Boland A. , Olaso R. , Meyer V. , Altmuller J. , Le Calvez-Kelm F. , Durand G. , Voegele C. , Boyault S. , Moonen L. , Lemaitre N. , Lorimier P. , Toffart A. C. , Soltermann A. , Clement J. H. , Saenger J. , Field J. K. , Brevet M. , Blanc-Fournier C. , Galateau-Salle F. , Le Stang N. , Russell P. A. , Wright G. , Sozzi G. , Pastorino U. , Lacomme S. , Vignaud J. M. , Hofman V. , Hofman P. , Brustugun O. T. , Lund-Iversen M. , Thomas de Montpreville V. , Muscarella L. A. , Graziano P. , Popper H. , Stojsic J. , Deleuze J. F. , Herceg Z. , Viari A. , Nuernberg P. , Pelosi G. , Dingemans A. M. C. , Milione M. , Roz L. , Brcic L. , Volante M. , Papotti M. G. , Caux C. , Sandoval J. , Hernandez-Vargas H. , Brambilla E. , Speel E. J. M. , Girard N. , Lantuejoul S. , McKay J. D. , Foll M. , Fernandez-Cuesta L. 
Published: August 2019

AbstractThe worldwide incidence of pulmonary carcinoids is increasing, but little is known about their molecular characteristics. Through machine learning and multi-omics factor analysis, we compare and contrast the genomic profiles of 116 pulmonary carcinoids (including 35 atypical), 75 large-cell neuroendocrine carcinomas (LCNEC), and 66 small-cell lung cancers. Here we report that the integrative analyses on 257 lung neuroendocrine neoplasms stratify atypical carcinoids into two prognostic groups with a 10-year overall survival of 88% and 27%, respectively. We identify therapeutically relevant molecular groups of pulmonary carcinoids, suggesting DLL3 and the immune system as candidate therapeutic targets; we confirm the value ofOTPexpression levels for the prognosis and diagnosis of these diseases, and we unveil the group of supra-carcinoids. This group comprises samples with carcinoid-like morphology yet the molecular and clinical features of the deadly LCNEC, further supporting the previously proposed molecular link between the low- and high-grade lung neuroendocrine neoplasms.
Ancient DNA from the skeletons of Roopkund Lake reveals Mediterranean migrants in India
Authors: Harney Éadaoin , Nayak Ayushi , Patterson Nick , Joglekar Pramod , Mushrif-Tripathy Veena , Mallick Swapan , Rohland Nadin , Sedig Jakob , Adamski Nicole , Bernardos Rebecca , Broomandkhoshbacht Nasreen , Culleton Brendan J. , Ferry Matthew , Harper Thomas K. , Michel Megan , Oppenheimer Jonas , Stewardson Kristin , Zhang Zhao , Harashawaradhana  , Bartwal Maanwendra Singh , Kumar Sachin , Diyundi Subhash Chandra , Roberts Patrick , Boivin Nicole , Kennett Douglas J. , Thangaraj Kumarasamy , Reich David , Rai Niraj 
Published: August 2019

AbstractSituated at over 5,000 meters above sea level in the Himalayan Mountains, Roopkund Lake is home to the scattered skeletal remains of several hundred individuals of unknown origin. We report genome-wide ancient DNA for 38 skeletons from Roopkund Lake, and find that they cluster into three distinct groups. A group of 23 individuals have ancestry that falls within the range of variation of present-day South Asians. A further 14 have ancestry typical of the eastern Mediterranean. We also identify one individual with Southeast Asian-related ancestry. Radiocarbon dating indicates that these remains were not deposited simultaneously. Instead, all of the individuals with South Asian-related ancestry date to ~800 CE (but with evidence of being deposited in more than one event), while all other individuals date to ~1800 CE. These differences are also reflected in stable isotope measurements, which reveal a distinct dietary profile for the two main groups.
Syringeable immunotherapeutic nanogel reshapes tumor microenvironment and prevents tumor metastasis and recurrence
Authors: Song Chanyoung , Phuengkham Hathaichanok , Kim Young Seob , Dinh Van Vuong , Lee Inho , Shin Il Woo , Shin Hong Sik , Jin Seung Mo , Um Soong Ho , Lee Hyunseung , Hong Kwan Soo , Jin Seon-Mi , Lee Eunji , Kang Tae Heung , Park Yeong-Min , Lim Yong Taik 
Published: August 2019

AbstractThe low response rate of current cancer immunotherapy suggests the presence of few antigen-specific T cells and a high number of immunosuppressive factors in tumor microenvironment (TME). Here, we develop a syringeable immunomodulatory multidomain nanogel (iGel) that overcomes the limitation by reprogramming of the pro-tumoral TME to antitumoral immune niches. Local and extended release of immunomodulatory drugs from iGel deplete immunosuppressive cells, while inducing immunogenic cell death and increased immunogenicity. When iGel is applied as a local postsurgical treatment, both systemic antitumor immunity and a memory T cell response are generated, and the recurrence and metastasis of tumors to lungs and other organs are significantly inhibited. Reshaping of the TME using iGel also reverts non-responding groups to checkpoint blockade therapies into responding groups. The iGel is expected as an immunotherapeutic platform that can reshape immunosuppressive TMEs and synergize cancer immunotherapy with checkpoint therapies, with minimized systemic toxicity.
Visualizing structural transitions of ligand-dependent gating of the TRPM2 channel
Authors: Yin Ying , Wu Mengyu , Hsu Allen L. , Borschel William F. , Borgnia Mario J. , Lander Gabriel C. , Lee Seok-Yong 
Published: August 2019

AbstractThe transient receptor potential melastatin 2 (TRPM2) channel plays a key role in redox sensation in many cell types. Channel activation requires binding of both ADP-ribose (ADPR) and Ca2+. The recently published TRPM2 structures from Danio rerio in the ligand-free and the ADPR/Ca2+-bound conditions represent the channel in closed and open states, which uncovered substantial tertiary and quaternary conformational rearrangements. However, it is unclear how these rearrangements are achieved within the tetrameric channel during channel gating. Here we report the cryo-electron microscopy structures of Danio rerio TRPM2 in the absence of ligands, in complex with Ca2+ alone, and with both ADPR and Ca2+, resolved to ~4.3 Å, ~3.8 Å, and ~4.2 Å, respectively. In contrast to the published results, our studies capture ligand-bound TRPM2 structures in two-fold symmetric intermediate states, offering a glimpse of the structural transitions that bridge the closed and open conformations.
Changes in Neuroimmune and Neuronal Death Markers after Adolescent Alcohol Exposure in Rats are Reversed by Donepezil
Authors: Swartzwelder H. S. , Healey Kati L. , Liu Wen , Dubester Kira , Miller Kelsey M. , Crews Fulton T. 
Published: August 2019

AbstractAdolescent intermittent ethanol (AIE) exposure diminishes neurogenesis and dendritic spine density in the dentate gyrus. The cholinesterase inhibitor, donepezil (Aricept), reverses AIE effects on dendritic spines, possibly by interacting with inflammatory and/or epigenetic mediators after AIE exposure. This study tests the hypothesis that donepezil reverses AIE-induced neuroimmune, and epigenetic changes in the adult dentate gyrus. Adolescent Sprague-Dawley male rats (PD30-43) were given 10 intermittent, intragastric doses of ethanol (5.0 g/kg) or isovolumetric water (AIW). Twenty-one days later half of the animals from each group were treated with either donepezil or isovolumetric water (i.g.) once daily for four days. Two hours after the last donepezil or water dose animals were sacrificed and brains prepared for immunohistochemical analyses. AIE reduced immunoreactivity for doublecortin (DCX) and increased immunoreactivity for activated caspase-3 and death receptor-3 in adulthood, suggesting an enduring attenuation of neurogenesis and an increase in progenitor death. These effects were reversed by donepezil treatment in adulthood. AIE also increased immunoreactivity for the inflammatory signaling molecules HMGB1 and RAGE, as well as the activated phosphorylated transcription factor pNFκB p65, and the gene silencing marker dimethylated histone H3K9. All of these AIE effects were also reversed by donepezil, with the exception of HMGB1.
Deep-sea Sediment Resuspension by Internal Solitary Waves in the Northern South China Sea
Authors: Jia Yonggang , Tian Zhuangcai , Shi Xuefa , Liu J. Paul , Chen Jiangxin , Liu Xiaolei , Ye Ruijie , Ren Ziyin , Tian Jiwei 
Published: August 2019

AbstractInternal solitary waves (ISWs) can cause strong vertical and horizontal currents and turbulent mixing in the ocean. These processes affect sediment and pollutant transport, acoustic transmissions and man-made structures in the shallow and deep oceans. Previous studies of the role of ISWs in suspending seafloor sediments and forming marine nepheloid layers were mainly conducted in shallow-water environments. In summer 2017, we observed at least four thick (70–140 m) benthic nepheloid layers (BNLs) at water depths between 956 and 1545 m over continental slopes in the northern South China Sea. We found there was a good correlation between the timing of the ISW packet and variations of the deepwater suspended sediment concentration (SSC). At a depth of 956 m, when the ISW arrived, the near-bottom SSC rapidly increased by two orders of magnitude to 0.62 mg/l at 8 m above the bottom. At two much deeper stations, the ISW-induced horizontal velocity reached 59.6–79.3 cm/s, which was one order of magnitude more than the seafloor contour currents velocity. The SSC, 10 m above the sea floor, rapidly increased to 0.10 mg/l (depth of 1545 m) and 1.25 mg/l (depth of 1252 m). In this study, we found that ISWs could suspend much more sediments on deepwater areas than previously thought. Specifically, we estimated that ISWs could induce and suspend 787 Mt/yr of sediment from shelf to deep-sea areas of the northern South China Sea. The total amount of sediment resuspended by shoaling ISWs was 2.7 times that of river-derived sediment reaching the northern South China Sea. This accounted for 6.1% of the global river-discharged sediment (16.4% of that from Asian rivers) transported to the sea.
Early changes in ammonia levels and liver function in patients with advanced hepatocellular carcinoma treated by lenvatinib therapy
Authors: Ohya Kazuki , Kawaoka Tomokazu , Namba Maiko , Uchikawa Shinsuke , Kodama Kenichiro , Morio Kei , Nakahara Takashi , Murakami Eisuke , Hiramatsu Akira , Tsuge Masataka , Yamauchi Masami , Imamura Michio , Chayama Kazuaki , Aikata Hiroshi 
Published: August 2019

AbstractWe aimed to investigate the early changes in ammonia levels and liver function in patients with advanced hepatocellular carcinoma treated with lenvatinib. This retrospective study included 23 patients with advanced hepatocellular carcinoma who were able to receive lenvatinib continuously for at least 1 week. We compared their ammonia levels (NH3), total bilirubin (Bil), albumin, and prothrombin (PT) activity at before and after 1 week of lenvatinib administration, and additionally, compared the 2 groups which were divided based on the presence/absence of portosystemic collaterals (PSCs). Before administration of lenvatinib the patients with PSCs had significantly worse ammonia levels and liver function than the patients without PSCs (NH3: P = 0.013, Bil: P = 0.004, PT: P = 0.047, respectively). Moreover, the indices were worse in all the patients after 1 week of lenvatinib than before administration (NH3: P = 0.001, Bil: P = 0.025, PT: P < 0.001, respectively). Moreover, the changes in ammonia levels were investigated for 4 weeks. The ammonia level increased, to peak at 2 weeks, but decreased after 3 weeks. None of the patients discontinued lenvatinib therapy because of an adverse event. The ammonia levels of the study patients increased from baseline at 1 week after lenvatinib administration, but therapy could be continued for 4 weeks by appropriate management.
The cortico-rubral and cerebello-rubral pathways are topographically organized within the human red nucleus
Authors: Cacciola Alberto , Milardi Demetrio , Basile Gianpaolo Antonio , Bertino Salvatore , Calamuneri Alessandro , Chillemi Gaetana , Paladina Giuseppe , Impellizzeri Federica , Trimarchi Fabio , Anastasi Giuseppe , Bramanti Alessia , Rizzo Giuseppina 
Published: August 2019

AbstractThe Red Nucleus (RN) is a large nucleus located in the ventral midbrain: it is subdivided into a small caudal magnocellular part (mRN) and a large rostral parvocellular part (pRN). These distinct structural regions are part of functionally different networks and show distinctive connectivity features: the mRN is connected to the interposed nucleus, whilst the pRN is mainly connected to dentate nucleus, cortex and inferior olivary complex. Despite functional neuroimaging studies suggest RN involvement in complex motor and higher order functions, the pRN and mRN cannot be distinguished using conventional MRI. Herein, we employ high-quality structural and diffusion MRI data of 100 individuals from the Human Connectome Project repository and constrained spherical deconvolution tractography to perform connectivity-based segmentation of the human RN. In particular, we tracked connections of RN with the inferior olivary complex, the interposed nucleus, the dentate nucleus and the cerebral cortex. We found that the RN can be subdivided according to its connectivity into two clusters: a large ventrolateral one, mainly connected with the cerebral cortex and the inferior olivary complex, and a smaller dorsomedial one, mainly connected with the interposed nucleus. This structural topography strongly reflects the connectivity patterns of pRN and mRN respectively. Structural connectivity-based segmentation could represent a useful tool for the identification of distinct subregions of the human red nucleus on 3T MRI thus allowing a better evaluation of this subcortical structure in healthy and pathological conditions.
Sex difference in IgE sensitization associated with alcohol consumption in the general population
Authors: Roh Daeyoung , Lee Dong-Hee , Lee Sang-Kyu , Kim Soo Whan , Kim Sung Won , Cho Jin Hee , Kim Byung-Guk , Shin Ji-Hyeon 
Published: August 2019

AbstractThe association of alcohol consumption and immunoglobulin E (IgE) sensitization is debated. Few population-based studies have investigated whether such associations differ by sex. We explored the association of alcohol consumption with IgE sensitization in the general population, stratified by sex. We analyzed data for 1,723 adults from the 2010 Korean National Health and Nutrition Examination Survey. We divided subjects into three groups according to their self-reported alcohol consumption or serum level of gamma-glutamyltransferase (GGT), an objective marker of alcohol consumption. After adjustments, the odds ratios (ORs) of male high-risk drinkers were 2.09 (95% confidence interval [CI], 1.34–3.28) for total IgE and 1.71 (95% CI, 1.03–2.83) forDermatophagoides farinae(DF)-specific IgE compared with male low-risk drinkers. In females, the dog-specific IgE level was associated with high-risk drinking (OR, 11.74; 95% CI, 2.04–67.24). The ORs of males in the high-serum-GGT group were 2.73 (95% CI, 1.72–4.33) for total IgE and 2.17 (95% CI, 1.35–3.47) for DF-specific IgE compared with those in the low-serum-GGT group. This study suggests a possible link between alcohol consumption and IgE sensitization, moreover, the risk of IgE sensitization was significantly higher in male high-risk drinkers. Therefore, clinicians should consider the risk of IgE sensitization possibly afflicting male high-risk drinkers.
ASIC3-dependent metabolomics profiling of serum and urine in a mouse model of fibromyalgia
Authors: Hsu Wei-Hsiang , Lee Cheng-Han , Chao Yen-Ming , Kuo Ching-Hua , Ku Wei-Chi , Chen Chih-Cheng , Lin Yun-Lian 
Published: August 2019

AbstractFibromyalgia (FM) is characterized by chronic widespread pain. The pathogenesis of FM remains unclear. No specific biomarkers are available. Animal models of FM may provide an opportunity to explore potential biomarkers in a relative homogenous disease condition. Here, we probed the metabolomics profiles of serum and urine in a mouse model of FM induced by intermittent cold stress (ICS). We focused on the role of acid-sensing ion channel 3 (ASIC3) in the metabolomics profiling because ICS treatment induced chronic widespread muscle pain lasting for 1 month in wild-type (Asic3+/+) but not Asic3-knockout (Asic3−/−) mice. Serum and urine samples were collected from both genotypes at different ICS stages, including before ICS (basal level) and post-ICS at days 10 (middle phase, P10) and 40 (recovery phase, P40). Control naïve mice and ICS-induced FM mice differed in 1H-NMR- and LC-MS-based metabolomics profiling. On pathway analysis, the leading regulated pathways in Asic3+/+ mice were taurine and hypotaurine, cysteine and methionine, glycerophospholipid, and ascorbate and aldarate metabolisms, and the major pathways in Asic3−/− mice involved amino acid-related metabolism. Finally, we developed an algorithm for the impactful metabolites in the FM model including cis-aconitate, kynurenate, taurine, pyroglutamic acid, pyrrolidonecarboxylic acid, and 4-methoxyphenylacetic acid in urine as well as carnitine, deoxycholic acid, lysoPC(16:0), lysoPC(20:3), oleoyl-L-carnitine, and trimethylamine N-oxide in serum. Asic3−/− mice were impaired in only muscle allodynia development but not other pain symptoms in the ICS model, so the ASIC3-dependent metabolomics changes could be useful for developing diagnostic biomarkers specific to chronic widespread muscle pain, the core symptom of FM. Further pharmacological validations are needed to validate these metabolomics changes as potential biomarkers for FM diagnosis and/or treatment responses.
A Rapid Method for Label-Free Enrichment of Rare Trophoblast Cells from Cervical Samples
Authors: Bailey-Hytholt Christina M. , Sayeed Sumaiya , Kraus Morey , Joseph Richard , Shukla Anita , Tripathi Anubhav 
Published: August 2019

AbstractExtravillous trophoblasts (EVTs) have the potential to provide the entire fetal genome for prenatal testing. Previous studies have demonstrated the presence of EVTs in the cervical canal and the ability to retrieve a small quantity of these cells by cervical sampling. However, these small quantities of trophoblasts are far outnumbered by the population of cervical cells in the sample, making isolation of the trophoblasts challenging. We have developed a method to enrich trophoblast cells from a cervical sample using differential settling of the cells in polystyrene wells. We tested the addition of small quantities of JEG-3 trophoblast cell line cells into clinical samples from standard Pap tests taken at 5 to 20 weeks of gestation to determine the optimal work flow. We observed that a 4 min incubation in the capture wells led to a maximum in JEG-3 cell settling on the surface (71 ± 10% of the initial amount added) with the removal of 91 ± 3% of the cervical cell population, leading to a 700% enrichment in JEG-3 cells. We hypothesized that settling of mucus in the cervical sample affects the separation. Finally, we performed a proof-of-concept study using our work flow and CyteFinder cell picking to verify enrichment and pick individual JEG-3 and trophoblast cells free of cervical cells. Ultimately, this work provides a rapid, facile, and cost-effective method for enriching native trophoblasts from cervical samples for use in subsequent non-invasive prenatal testing using methods including single cell picking.
Antiviral activity of ethanol extract of Geranii Herba and its components against influenza viruses via neuraminidase inhibition
Authors: Choi Jang-Gi , Kim Young Soo , Kim Ji Hye , Chung Hwan-Suck 
Published: August 2019

AbstractInfluenza viruses are a serious threat to human health, causing numerous deaths and pandemics worldwide. To date, neuraminidase (NA) inhibitors have primarily been used to treat influenza. However, there is a growing need for novel NA inhibitors owing to the emergence of resistant viruses. Geranii Herba (Geranium thunbergii Siebold et Zuccarini), which is edible, has long been used in a variety of disease treatments in Asia. Although recent studies have reported its various pharmacological activities, the effect of Geranii Herba and its components on influenza viruses has not yet been reported. In this study, Geranii Herba ethanol extract (GHE) and its component geraniin showed high antiviral activity against influenza A strain as well as influenza B strain, against which oseltamivir has less efficacy than influenza A strain, by inhibiting NA activity following viral infection in Madin–Darby canine kidney cells. Thus, GHE and its components may be useful for the development of anti-influenza drugs.
Graphene oxide-ferrite hybrid framework as enhanced broadband absorption in gigahertz frequencies
Authors: Bhattacharyya Rajarshi , Prakash Om , Roy Somnath , Singh Akhilendra Pratap , Bhattacharya Tapas Kumar , Maiti Pralay , Bhattacharyya Somak , Das Santanu 
Published: August 2019

AbstractThe present investigation is focused on the in-situ synthesis of Graphene oxide (GO)-ferrite nanoparticle hybrid framework by gel-combustion method followed by fabrication of homogeneous, structurally stable thin (~100–120 μm) hybrid-polyurethane coating on a metallic aluminum substrate and its application on the properties of broadband absorption over the microwave frequency region. Microstructure studies of hybrid materials illustrated that small sized ferrite nanoparticles (~17 nm) are grafted on and through the graphene layers, which forms a homogeneous coating thereby. The hybrid-nanocomposite coating demonstrated superior broadband absorption properties with absorptivity higher than 90% throughout a bandwidth of ~6 GHz, and moreover, it was found that with increased loading of GO in the nanocomposite, the bandwidth range of absorption frequency increases with enhanced absorptivity. The real part and imaginary part of the surface impedance values of the coating was obtained as 377 Ω and 0 Ω, respectively, which imply that the free-space impedance of the hybrid-nanocomposite coating is matching correctly. The nanocomposite coating showed ultra-high absorptivity over the frequency band of 8–12 GHz, which has numerous practical applications as radar absorbing materials (RAM), stealth technology, electromagnetic shielding, and radiated electromagnetic interference (EMI) management in onboard spacecraft and many more.