bluuebunny/crossref_metadata_2025_split huggingface dataset:
Citalopram-induced pathways regulation and tentative treatment-outcome-predicting biomarkers in lymphoblastoid cell lines from depression patients
Authors: Barakat Abdul Karim , Scholl Catharina , Steffens Michael , Brandenburg Kerstin , Ising Marcus , Lucae Susanne , Holsboer Florian , Laje Gonzalo , Kalayda Ganna V. , Jaehde Ulrich , Stingl Julia Carolin 
Published: July 2020

AbstractAntidepressant therapy is still associated with delays in symptomatic improvement and low response rates. Incomplete understanding of molecular mechanisms underlying antidepressant effects hampered the identification of objective biomarkers for antidepressant response. In this work, we studied transcriptome-wide expression followed by pathway analysis in lymphoblastoid cell lines (LCLs) derived from 17 patients documented for response to SSRI antidepressants from the Munich Antidepressant Response Signatures (MARS) study upon short-term incubation (24 and 48 h) with citalopram. Candidate transcripts were further validated with qPCR in MARS LCLs from responders (n = 33) vs. non-responders (n = 36) and afterward in an independent cohort of treatment-resistant patients (n = 20) vs. first-line responders (n = 24) from the STAR*D study. In MARS cohort we observed significant associations of GAD1 (glutamate decarboxylase 1; p = 0.045), TBC1D9 (TBC1 Domain Family Member 9; p = 0.014–0.021) and NFIB (nuclear factor I B; p = 0.015–0.025) expression with response status, remission status and improvement in depression scale, respectively. Pathway analysis of citalopram-altered gene expression indicated response-status-dependent transcriptional reactions. Whereas in clinical responders neural function pathways were primarily up- or downregulated after incubation with citalopram, deregulated pathways in non-responders LCLs mainly involved cell adhesion and immune response. Results from the STAR*D study showed a marginal association of treatment-resistant depression with NFIB (p = 0.068) but not with GAD1 (p = 0.23) and TBC1D9 (p = 0.27). Our results propose the existence of distinct pathway regulation mechanisms in responders vs. non-responders and suggest GAD1, TBC1D9, and NFIB as tentative predictors for clinical response, full remission, and improvement in depression scale, respectively, with only a weak overlap in predictors of different therapy outcome phenotypes.
A genome-wide scan for pleiotropy between bone mineral density and nonbone phenotypes
Authors: Christou Maria A. , Ntritsos Georgios , Markozannes Georgios , Koskeridis Fotis , Nikas Spyros N. , Karasik David , Kiel Douglas P. , Evangelou Evangelos , Ntzani Evangelia E. 
Published: July 2020

AbstractOsteoporosis is the most common metabolic bone disorder globally and is characterized by skeletal fragility and microarchitectural deterioration. Genetic pleiotropy occurs when a single genetic element is associated with more than one phenotype. We aimed to identify pleiotropic loci associated with bone mineral density (BMD) and nonbone phenotypes in genome-wide association studies. In the discovery stage, the NHGRI-EBI Catalog was searched for genome-wide significant associations (P value < 5 × 10−8), excluding bone-related phenotypes. SNiPA was used to identify proxies of the significantly associated single nucleotide polymorphisms (SNPs) (r2 = 1). We then assessed putative genetic associations of this set of SNPs with femoral neck (FN) and lumbar spine (LS) BMD data from the GEFOS Consortium. Pleiotropic variants were claimed at a false discovery rate < 1.4 × 10−3 for FN-BMD and < 1.5 × 10−3 for LS-BMD. Replication of these genetic markers was performed among more than 400 000 UK Biobank participants of European ancestry with available genetic and heel bone ultrasound data. In the discovery stage, 72 BMD-related pleiotropic SNPs were identified, and 12 SNPs located in 11 loci on 8 chromosomes were replicated in the UK Biobank. These SNPs were associated, in addition to BMD, with 14 different phenotypes. Most pleiotropic associations were exhibited by rs479844 (AP5B1, OVOL1 genes), which was associated with dermatological and allergic diseases, and rs4072037 (MUC1 gene), which was associated with magnesium levels and gastroenterological cancer. In conclusion, 12 BMD-related genome-wide significant SNPs showed pleiotropy with nonbone phenotypes. Pleiotropic associations can deepen the genetic understanding of bone-related diseases by identifying shared biological mechanisms with other diseases or traits.
A FAK/HDAC5 signaling axis controls osteocyte mechanotransduction
Authors: Sato Tadatoshi , Verma Shiv , Andrade Christian D. Castro , Omeara Maureen , Campbell Nia , Wang Jialiang S. , Cetinbas Murat , Lang Audrey , Ausk Brandon J. , Brooks Daniel J. , Sadreyev Ruslan I. , Kronenberg Henry M. , Lagares David , Uda Yuhei , Pajevic Paola Divieti , Bouxsein Mary L. , Gross Ted S. , Wein Marc N. 
Published: July 2020

AbstractOsteocytes, cells ensconced within mineralized bone matrix, are the primary skeletal mechanosensors. Osteocytes sense mechanical cues by changes in fluid flow shear stress (FFSS) across their dendritic projections. Loading-induced reductions of osteocytic Sclerostin (encoded by Sost) expression stimulates new bone formation. However, the molecular steps linking mechanotransduction and Sost suppression remain unknown. Here, we report that class IIa histone deacetylases (HDAC4 and HDAC5) are required for loading-induced Sost suppression and bone formation. FFSS signaling drives class IIa HDAC nuclear translocation through a signaling pathway involving direct HDAC5 tyrosine 642 phosphorylation by focal adhesion kinase (FAK), a HDAC5 post-translational modification that controls its subcellular localization. Osteocyte cell adhesion supports FAK tyrosine phosphorylation, and FFSS triggers FAK dephosphorylation. Pharmacologic FAK catalytic inhibition reduces Sost mRNA expression in vitro and in vivo. These studies demonstrate a role for HDAC5 as a transducer of matrix-derived cues to regulate cell type-specific gene expression.
High-altitude populations need special considerations for COVID-19
Authors: Breevoort Arnar , Carosso Giovanni A. , Mostajo-Radji Mohammed A. 
Published: July 2020

AbstractThe atmospheric pressure that decreases with altitude affects lung physiology. However, these changes in physiology are not usually considered in ventilator design and testing. We argue that high altitude human populations require special attention to access the international supply of ventilators.
Reliability of R2R-printed, flexible electrodes for e-clothing applications
Authors: Sliz Rafal , Huttunen Olli-Heikki , Jansson Elina , Kemppainen Juhani , Schroderus Jyrki , Kurkinen Marika , Fabritius Tapio 
Published: July 2020

AbstractConformable electrodes are essential for the development of flexible electronics or functional clothing, regardless of their application. Their reliable ability to transfer electric signals or serve as sensing elements in various conditions is vital for the advancement of wearables that will enhance our everyday life. In this research, we concentrate our efforts on the understanding of the influence of elongation and washing on roll-to-roll printed conductive electrodes of various shapes and materials. A large sample set provides data on the breaking mechanisms and how these affect the electrical properties of the electrodes. In addition, the physicochemical analysis offers insights into the electrodes’ and materials’ behavior in extreme conditions during elongation and washing cycles. The achieved results indicate auspicious nanoparticle shapes and sizes as well as evidence regarding micro-scale breaking mechanisms responsible for electrodes degradation. Utilization of commercially available materials and roll-to-roll printing techniques allow the seamless application of achieved results and the creation of more reliable, flexible electronic devices.
Using generalized additive models to investigate the environmental effects on pipe failure in clean water networks
Authors: Barton Neal Andrew , Farewell Timothy Stephen , Hallett Stephen Henry 
Published: July 2020

AbstractPredicting pipe failures using statistical modelling benefits from detailed knowledge of the conditions and circumstances which influence such failures. Incorporating this knowledge into model building improves failure predictions. In this study, we model weather, soil and hydrogeological variables in a generalized additive model for five common pipe materials separately, using partial dependence plots to understand the partial effects of each variable on pipe failure. We show how severe temperatures are associated with high pipe failure. Cold temperatures and air frost and their interaction with soils represent the key factors for pipe failures during the winter for metal pipes. Warm temperatures, high soil moisture deficit and soil movement results in higher pipe failures in asbestos cement pipes during the summer. Warm temperatures, ground movement and soil wash out, and water demand are key factors for polyvinyl chloride pipe failure during the summer. Frost is a key factor influencing polyethylene pipes during winter. An understanding of the physical principals concerning pipe failures can enable the development of more accurate models, guiding network management plans to help reduce asset leakage through appropriate interventions.
Heterotopic Porcine Cardiac Xenotransplantation in the Intra-Abdominal Position in a Non-Human Primate Model
Authors: Goerlich Corbin E. , DiChiacchio Laura , Zhang Tianshu , Singh Avneesh K. , Lewis Billeta , Tatarov Ivan , Hershfeld Alena , Sentz Faith , Ayares David , Corcoran Philip , Horvath Keith , Mohiuddin Muhammad M. 
Published: July 2020

AbstractHeterotopic cardiac transplantation in the intra-abdominal position in a large animal model has been essential in the progression of the field of cardiac transplantation. Our group has over 10 years of experience in cardiac xenotransplantation with pig to baboon models, the longest xenograft of which survived over 900 days, with rejection only after reducing immunosuppression. This article aims to clarify our approach to this model in order to allow others to share success in long-term survival. Here, we demonstrate the approach to implantation of a cardiac graft into the intra-abdominal position in a baboon recipient for the study of transplantation and briefly highlight our model’s ability to provide insight into not only xenotransplantation but across disciplines. We include details that have provided us with consistent success in this model; performance of the anastomoses, de-airing of the graft, implantation of a long-term telemetry device for invasive graft monitoring, and ideal geometric positioning of the heart and telemetry device in the limited space of the recipient abdomen. We additionally detail surveillance techniques to assess long-term graft function.
Hybrid biocomposites from polypropylene, sustainable biocarbon and graphene nanoplatelets
Authors: Watt Ethan , Abdelwahab Mohamed A. , Snowdon Michael R. , Mohanty Amar K. , Khalil Hamdy , Misra Manjusri 
Published: July 2020

AbstractPolypropylene (PP) is an attractive polymer for use in automotive parts due to its ease of processing, hydrophobic nature, chemical resistance and low density. The global shift towards eliminating non-renewable resource consumption has promoted research of sustainable biocarbon (BioC) filler in a PP matrix, but this material often leads to reduction in composite strength and requires additional fillers. Graphene nano-platelets (GnPs) have been the subject of considerable research as a nanofiller due to their strength, while maleic anhydride grafted polypropylene (MA-g-PP) is a commonly used compatibilizer for improvement of interfacial adhesion in composites. This study compared the thermo-mechanical properties of PP/BioC/MA-g-PP/GnP composites with varying wt.% of GnP. Morphological analysis revealed uniform dispersion of BioC, while significant agglomeration of GnPs limited their even dispersion throughout the PP matrix. In the optimal blend of 3 wt.% GnP and 17 wt.% BioC biocontent, tensile strength and modulus increased by ~19% and ~22% respectively, as compared to 20 wt.% BioC biocomposites. Thermal stability and performance enhancement occurred through incorporation of the fillers. Thus, hybridization of fillers in the compatibilized matrix presents a promising route to the enhancement of material properties, while reducing petroleum-based products through use of sustainable BioC filler in composite structures.
Mesenchymal subtype neuroblastomas are addicted to TGF-βR2/HMGCR-driven protein geranylgeranylation
Authors: Stokes Michael E. , Small Jonnell Candice , Vasciaveo Alessandro , Shimada Kenichi , Hirschhorn Tal , Califano Andrea , Stockwell Brent R. 
Published: July 2020

AbstractThe identification of targeted agents with high therapeutic index is a major challenge for cancer drug discovery. We found that screening chemical libraries across neuroblastoma (NBL) tumor subtypes for selectively-lethal compounds revealed metabolic dependencies that defined each subtype. Bioactive compounds were screened across cell models of mesenchymal (MESN) and MYCN-amplified (MYCNA) NBL subtypes, which revealed the mevalonate and folate biosynthetic pathways as MESN-selective dependencies. Treatment with lovastatin, a mevalonate biosynthesis inhibitor, selectively inhibited protein prenylation and induced apoptosis in MESN cells, while having little effect in MYCNA lines. Statin sensitivity was driven by HMGCR expression, the rate-limiting enzyme for cholesterol synthesis, which correlated with statin sensitivity across NBL cell lines, thus providing a drug sensitivity biomarker. Comparing expression profiles from sensitive and resistant cell lines revealed a TGFBR2 signaling axis that regulates HMGCR, defining an actionable addiction in that leads to MESN-subtype-dependent apoptotic cell death.
Validation of the four-miRNA biomarker panel MiCaP for prediction of long-term prostate cancer outcome
Authors: Strand Siri H. , Schmidt Linnéa , Weiss Simone , Borre Michael , Kristensen Helle , Rasmussen Anne Karin Ildor , Daugaard Tina Fuglsang , Kristensen Gitte , Stroomberg Hein Vincent , Røder Martin Andreas , Brasso Klaus , Mouritzen Peter , Sørensen Karina Dalsgaard 
Published: July 2020

AbstractImproved prostate cancer prognostic biomarkers are urgently needed. We previously identified the four-miRNA prognostic biomarker panel MiCaP ((miR-23a-3p × miR-10b-5p)/(miR-133a-3p × miR-374b-5p)) for prediction of biochemical recurrence (BCR) after radical prostatectomy (RP). Here, we identified an optimal numerical cut-off for MiCaP dichotomisation using a training cohort of 475 RP patients and tested this in an independent cohort of 281 RP patients (PCA281). Kaplan–Meier, uni- and multivariate Cox regression analyses were conducted for multiple endpoints: BCR, metastatic-(mPC) and castration-resistant prostate cancer (CRPC), prostate cancer-specific (PCSS) and overall survival (OS). Functional effects of the four MiCaP miRNAs were assessed by overexpression and inhibition experiments in prostate cancer cell lines. We found the numerical value 5.709 optimal for MiCaP dichotomisation. This was independently validated in PCA281, where a high MiCaP score significantly [and independent of the Cancer of the Prostate Risk Assessment Postsurgical (CAPRA-S) score] predicted BCR, progression to mPC and CRPC, and PCSS, but not OS. Harrell’s C-index increased upon addition of MiCaP to CAPRA-S for all endpoints. Inhibition of miR-23a-3p and miR-10b-5p, and overexpression of miR-133a-3p and miR-374b-5p significantly reduced cell survival. Our results may promote future implementation of a MiCaP-based test for improved prostate cancer risk stratification.
The mitogenome portrait of Umbria in Central Italy as depicted by contemporary inhabitants and pre-Roman remains
Authors: Modi Alessandra , Lancioni Hovirag , Cardinali Irene , Capodiferro Marco R. , Rambaldi Migliore Nicola , Hussein Abir , Strobl Christina , Bodner Martin , Schnaller Lisa , Xavier Catarina , Rizzi Ermanno , Bonomi Ponzi Laura , Vai Stefania , Raveane Alessandro , Cavadas Bruno , Semino Ornella , Torroni Antonio , Olivieri Anna , Lari Martina , Pereira Luisa , Parson Walther , Caramelli David , Achilli Alessandro 
Published: July 2020

AbstractUmbria is located in Central Italy and took the name from its ancient inhabitants, theUmbri, whose origins are still debated. Here, we investigated the mitochondrial DNA (mtDNA) variation of 545 present-day Umbrians (with 198 entire mitogenomes) and 28 pre-Roman individuals (obtaining 19 ancient mtDNAs) excavated from the necropolis ofPlestia. We found a rather homogeneous distribution of western Eurasian lineages across the region, with few notable exceptions. Contemporary inhabitants of the eastern part, delimited by the Tiber River and the Apennine Mountains, manifest a peculiar mitochondrial proximity to central-eastern Europeans, mainly due to haplogroups U4 and U5a, and an overrepresentation of J (30%) similar to the pre-Roman remains, also excavated in East Umbria. Local genetic continuities are further attested to by six terminal branches (H1e1, J1c3, J2b1, U2e2a, U8b1b1 and K1a4a) shared between ancient and modern mitogenomes. Eventually, we identified multiple inputs from various population sources that likely shaped the mitochondrial gene pool of ancientUmbriover time, since early Neolithic, including gene flows with central-eastern Europe. This diachronic mtDNA portrait of Umbria fits well with the genome-wide population structure identified on the entire peninsula and with historical sources that list theUmbriamong the most ancient Italic populations.
Skewed electronic band structure induced by electric polarization in ferroelectric BaTiO3
Authors: Oshime Norihiro , Kano Jun , Ikenaga Eiji , Yasui Shintaro , Hamasaki Yosuke , Yasuhara Sou , Hinokuma Satoshi , Ikeda Naoshi , Janolin Pierre-Eymeric , Kiat Jean-Michel , Itoh Mitsuru , Yokoya Takayoshi , Fujii Tatsuo , Yasui Akira , Osawa Hitoshi 
Published: July 2020

AbstractSkewed band structures have been empirically described in ferroelectric materials to explain the functioning of recently developed ferroelectric tunneling junction (FTJs). Nonvolatile ferroelectric random access memory (FeRAM) and the artificial neural network device based on the FTJ system are rapidly developing. However, because the actual ferroelectric band structure has not been elucidated, precise designing of devices has to be advanced through appropriate heuristics. Here, we perform angle-resolved hard X-ray photoemission spectroscopy of ferroelectric BaTiO3 thin films for the direct observation of ferroelectric band skewing structure as the depth profiles of atomic orbitals. The depth-resolved electronic band structure consists of three depth regions: a potential slope along the electric polarization in the core, the surface and interface exhibiting slight changes. We also demonstrate that the direction of the energy shift is controlled by the polarization reversal. In the ferroelectric skewed band structure, we found that the difference in energy shifts of the atomic orbitals is correlated with the atomic configuration of the soft phonon mode reflecting the Born effective charges. These findings lead to a better understanding of the origin of electric polarization.
Role of water in cyclooxygenase catalysis and design of anti-inflammatory agents targeting two sites of the enzyme
Authors: Kaur Manpreet , Kaur Baljit , Kaur Jagroop , Kaur Anudeep , Bhatti Rajbir , Singh Palwinder 
Published: July 2020

AbstractWhile designing the anti-inflammatory agents targeting cyclooxygenase-2 (COX-2), we first identified a water loop around the heme playing critical role in the enzyme catalysis. The results of molecular dynamic studies supported by the strong hydrogen-bonding equilibria of the participating atoms, radical stabilization energies, the pKa of the H-donor/acceptor sites and the cyclooxygenase activity of pertinent muCOX-2 ravelled the working of the water–peptide channel for coordinating the flow of H·/electron between the heme and Y385. Based on the working of H·/electron transfer channel between the 12.5 Å distant radical generation and the radical disposal sites, a series of molecules was designed and synthesized. Among this category of compounds, an appreciably potent anti-inflammatory agent exhibiting IC50 0.06 μM against COX-2 and reversing the formalin induced analgesia and carageenan induced inflammation in mice by 90% was identified. Further it was revealed that, justifying its bidentate design, the compound targets water loop (heme bound site) and the arachidonic acid binding pockets of COX-2.
Late subadult ontogeny and adult aging of the human thorax reveals divergent growth trajectories between sexes
Authors: García-Martínez Daniel , Bastir Markus , Villa Chiara , García-Río Francisco , Torres-Sánchez Isabel , Recheis Wolfgang , Barash Alon , Khonsari Roman Hossein , O’Higgins Paul , Meyer Marc R. , Heuzé Yann 
Published: July 2020

AbstractSexual dimorphism is an important feature of adult thorax morphology, but when and how sex-related differences in the ribcage arise during ontogeny is poorly known. Previous research proposed that sex-related size differences in the nasal region arise during puberty. Therefore, we explore whether ribcage sexual dimorphism also arises at that time and whether this sexual dimorphism is maintained until old age. We measured 526 (semi)landmarks on 80 CT-based human ribcage reconstructions, on individuals ranging from 7 to 65 year-old. The 3D coordinates were submitted to the Procrustes superimposition and analyzed. Our results show that the trajectories of thorax size and shape between sexes diverge at around 12 years of age, and continue slightly diverging until old age. The differential ontogenetic trends cause adult male ribcages to become deeper, shorter, and wider than female. Our results are consistent with the evidence from the cranial respiratory system, with the development of sexual dimorphism probably related to changes in body composition during puberty combined with changes in the reproductive system.
Impact of immune-mediated diseases in inflammatory bowel disease and implications in therapeutic approach
Authors: García M. J. , Pascual M. , Del Pozo C. , Díaz-González A. , Castro B. , Rasines L. , Crespo J. , Rivero M. 
Published: July 2020

AbstractInflammatory bowel diseases (IBD) belong to the group of immune-mediated diseases (IMIDs). The effect of associated IMIDs in the prognosis in IBD is nowadays unknown. To describe IMIDs associated to IBD patients and evaluate differences linked to the presence or absence of IMIDs. A unicentric retrospective descriptive study was designed. A cohort of 1,448 patients were categorized according to the presence of IMIDs. Clinical characteristics were obtained from IBD database. Univariate and multivariate analysis were performed. 385 patients were diagnosed with associated IMIDs while 1,063 had no associated IMIDs. A prevalence of 26.6% IMIDs associated to IBD was observed. Asthma, skin psoriasis and rheumatoid diseases were most commonly found. Factors associated to the presence of IMIDs were women (OR 1.48; 95 CI 1.17–1.87) and Crohn’s disease (OR 1.35; 95 CI 1.07–1.70). Patients with associated IMIDs required more immunomodulator (OR 1.61; 95 CI 1.27–2.43) and biological treatment (OR 1.81; 95 CI 1.47–2.43). More surgical risk was observed in multivariate analysis in those patients diagnosed with IMIDs prior to the onset of IBD (OR 3.71; 95% CI 2.1–6.56). We considered the presence of IMIDs a poor prognostic factor and suggest a closer monitoring of these patients.