bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mitigating osteonecrosis of the jaw (ONJ) through preventive dental care and understanding of risk factors
Authors: Wan Jason T. , Sheeley Douglas M. , Somerman Martha J. , Lee Janice S. 
Published: March 2020

AbstractIt is well established that alterations in phosphate metabolism have a profound effect on hard and soft tissues of the oral cavity. The present-day clinical form of osteonecrosis of the jaw (ONJ) was preceded by phosphorus necrosis of the jaw, ca. 1860. The subsequent removal of yellow phosphorus from matches in the early 20th century saw a parallel decline in “phossy jaw” until the early 2000s, when similar reports of unusual jaw bone necrosis began to appear in the literature describing jaw necrosis in patients undergoing chemotherapy and concomitant steroid and bisphosphonate treatment. Today, the potential side effect of ONJ associated with medications that block osteoclast activity (antiresorptive) is well known, though the mechanism remains unclear and the management and outcomes are often unsatisfactory. Much of the existing literature has focused on the continuing concerns of appropriate use of bisphosphonates and other antiresorptive medications, the incomplete or underdeveloped research on ONJ, and the use of drugs with anabolic potential for treatment of osteoporosis. While recognizing that ONJ is a rare occurrence and ONJ-associated medications play an important role in fracture risk reduction in osteoporotic patients, evidence to date suggests that health care providers can lower the risk further by dental evaluations and care prior to initiating antiresorptive therapies and by monitoring dental health during and after treatment. This review describes the current clinical management guidelines for ONJ, the critical role of dental-medical management in mitigating risks, and the current understanding of the effects of predominantly osteoclast-modulating drugs on bone homeostasis.
TFEB-mediated lysosomal biogenesis and lysosomal drug sequestration confer resistance to MEK inhibition in pancreatic cancer
Authors: Zhao Ben , Dierichs Laura , Gu Jiang-Ning , Trajkovic-Arsic Marija , Axel Hilger Ralf , Savvatakis Konstantinos , Vega-Rubin-de-Celis Silvia , Liffers Sven-Thorsten , Peña-Llopis Samuel , Behrens Diana , Hahn Stephan , Siveke Jens T. , Lueong Smiths S. 
Published: March 2020

AbstractOncogenic KRAS mutations are encountered in more than 90% of pancreatic ductal adenocarcinomas. MEK inhibition has failed to procure any clinical benefits in mutant RAS-driven cancers including pancreatic ductal adenocarcinoma (PDAC). To identify potential resistance mechanisms underlying MEK inhibitor (MEKi) resistance in PDAC, we investigated lysosomal drug accumulation in PDAC models both in vitro and in vivo. Mouse PDAC models and human PDAC cell lines as well as human PDAC xenografts treated with the MEK inhibitor trametinib or refametinib led to an enhanced expression of lysosomal markers and enrichment of lysosomal gene sets. A time-dependent, increase in lysosomal content was observed upon MEK inhibition. Strikingly, there was a strong activation of lysosomal biogenesis in cell lines of the classical compared to the basal-like molecular subtype. Increase in lysosomal content was associated with nuclear translocation of the Transcription Factor EB (TFEB) and upregulation of TFEB target genes. siRNA-mediated depletion of TFEB led to a decreased lysosomal biogenesis upon MEK inhibition and potentiated sensitivity. Using LC-MS, we show accumulation of MEKi in the lysosomes of treated cells. Therefore, MEK inhibition triggers lysosomal biogenesis and subsequent drug sequestration. Combined targeting of MEK and lysosomal function may improve sensitivity to MEK inhibition in PDAC.
Red blood cell-derived semaphorin 7A promotes thrombo-inflammation in myocardial ischemia-reperfusion injury through platelet GPIb
Authors: Köhler David , Granja Tiago , Volz Julia , Koeppen Michael , Langer Harald F. , Hansmann Georg , Legchenko Ekaterina , Geisler Tobias , Bakchoul Tamam , Eggstein Claudia , Häberle Helene A. , Nieswandt Bernhard , Rosenberger Peter 
Published: March 2020

AbstractMyocardial ischemia is one of the leading health problems worldwide. Therapy consists of the restitution of coronary perfusion which is followed by myocardial inflammation. Platelet–neutrophil interaction is a crucial process during inflammation, yet its consequences are not fully understood. Here, we show that platelet–neutrophil complexes (PNCs) are increased in patients with acute myocardial infarction and that this is associated with increased levels of neuronal guidance protein semaphorin 7A (SEMA7A). To investigate this further, we injected WT animals with Sema7a and found increased infarct size with increased numbers of PNCs. Experiments in genetically modified animals identify Sema7a on red blood cells to be crucial for this condition. Further studies revealed that Sema7a interacts with the platelet receptor glycoprotein Ib (GPIb). Treatment with anti-Sema7a antibody protected from myocardial tissue injury. In summary, we show that Sema7a binds to platelet GPIb and enhances platelet thrombo-inflammatory activity, aggravating post-ischemic myocardial tissue injury.
The lipoprotein Pal stabilises the bacterial outer membrane during constriction by a mobilisation-and-capture mechanism
Authors: Szczepaniak Joanna , Holmes Peter , Rajasekar Karthik , Kaminska Renata , Samsudin Firdaus , Inns Patrick George , Rassam Patrice , Khalid Syma , Murray Seán M. , Redfield Christina , Kleanthous Colin 
Published: March 2020

AbstractCoordination of outer membrane constriction with septation is critical to faithful division in Gram-negative bacteria and vital to the barrier function of the membrane. This coordination requires the recruitment of the peptidoglycan-binding outer-membrane lipoprotein Pal at division sites by the Tol system. Here, we show that Pal accumulation at Escherichia coli division sites is a consequence of three key functions of the Tol system. First, Tol mobilises Pal molecules in dividing cells, which otherwise diffuse very slowly due to their binding of the cell wall. Second, Tol actively captures mobilised Pal molecules and deposits them at the division septum. Third, the active capture mechanism is analogous to that used by the inner membrane protein TonB to dislodge the plug domains of outer membrane TonB-dependent nutrient transporters. We conclude that outer membrane constriction is coordinated with cell division by active mobilisation-and-capture of Pal at division septa by the Tol system.
Genome assembly of six polyploid potato genomes
Authors: Kyriakidou Maria , Anglin Noelle L. , Ellis David , Tai Helen H. , Strömvik Martina V. 
Published: March 2020

AbstractGenome assembly of polyploid plant genomes is a laborious task as they contain more than two copies of the genome, are often highly heterozygous with a high level of repetitive DNA. Next Generation genome sequencing data representing one Chilean and five Peruvian polyploid potato (Solanum spp.) landrace genomes was used to construct genome assemblies comprising five taxa. Third Generation sequencing data (Linked and Long-read data) was used to improve the assembly for one of the genomes. Native landraces are valuable genetic resources for traits such as disease and pest resistance, environmental tolerance and other qualities of interest such as nutrition and fiber for breeding programs. The need for conservation and enhanced understanding of genetic diversity of cultivated potato from South America is also crucial to North American and European cultivars. Here, we report draft genomes from six polyploid potato landraces representing five taxa, illustrating how Third Generation Sequencing can aid in assembling polyploid genomes.
Crosstalk reduction of integrated optical waveguides with nonuniform subwavelength silicon strips
Authors: Yang Yang , Guo Yinghui , Huang Yijia , Pu Mingbo , Wang Yanqin , Ma Xiaoliang , Li Xiong , Luo Xiangang 
Published: March 2020

AbstractSuppression of the crosstalk between adjacent waveguides is important yet challenging in the development of compact and dense photonic integrated circuits (PICs). During the past few years, a few of excellent approaches have been proposed to achieve this goal. Here, we propose a novel strategy by introducing nonuniform subwavelength strips between adjacent waveguides. In order to determine the widths and positions of nonuniform subwavelength strips, the particle swarm optimization (PSO) algorithm is utilized. Numerical results demonstrate that the coupling length between adjacent waveguides is increased by three (five) orders of magnitude in comparison with the case of uniform (no) subwavelength strips. Our method greatly reduces crosstalk and is expected to achieve a highly compact integrated density of PICs.
Comprehensive transcriptome profiling of Taiwanese colorectal cancer implicates an ethnic basis for pathogenesis
Authors: Wu Shao-Min , Tsai Wen-Sy , Chiang Sum-Fu , Lai Yi-Hsuan , Ma Chung-Pei , Wang Jian-Hua , Lin Jiarong , Lu Pei-Shan , Yang Chia-Yu , Tan Bertrand Chin-Ming , Liu Hsuan 
Published: March 2020

AbstractColorectal cancer (CRC) is one of the most commonly diagnosed cancers worldwide. While both genetic and environmental factors have been linked to the incidence and mortality associated with CRC, an ethnic aspect of its etiology has also emerged. Since previous large-scale cancer genomics studies are mostly based on samples of European ancestry, the patterns of clinical events and associated mechanisms in other minority ethnic patients suffering from CRC are largely unexplored. We collected 104 paired and adjacent normal tissue and CRC tumor samples from Taiwanese patients and employed an integrated approach – paired expression profiles of mRNAs and microRNAs (miRNAs) combined with transcriptome-wide network analyses – to catalog the molecular signatures of this regional cohort. On the basis of this dataset, which is the largest ever reported for this type of systems analysis, we made the following key discoveries: (1) In comparison to the The Cancer Genome Atlas (TCGA) data, the Taiwanese CRC tumors show similar perturbations in expressed genes but a distinct enrichment in metastasis-associated pathways. (2) Recurrent as well as novel CRC-associated gene fusions were identified based on the sequencing data. (3) Cancer subtype classification using existing tools reveals a comparable distribution of tumor subtypes between Taiwanese cohort and TCGA datasets; however, this similarity in molecular attributes did not translate into the predicted subtype-related clinical outcomes (i.e., death event). (4) To further elucidate the molecular basis of CRC prognosis, we developed a new stratification strategy based on miRNA–mRNA-associated subtyping (MMAS) and consequently showed that repressed WNT signaling activity is associated with poor prognosis in Taiwanese CRC. In summary, our findings of distinct, hitherto unreported biosignatures underscore the heterogeneity of CRC tumorigenesis, support our hypothesis of an ethnic basis of disease, and provide prospects for translational medicine.
Light organ photosensitivity in deep-sea shrimp may suggest a novel role in counterillumination
Authors: Bracken-Grissom Heather D. , DeLeo Danielle M. , Porter Megan L. , Iwanicki Tom , Sickles Jamie , Frank Tamara M. 
Published: March 2020

AbstractExtraocular photoreception, the ability to detect and respond to light outside of the eye, has not been previously described in deep-sea invertebrates. Here, we investigate photosensitivity in the bioluminescent light organs (photophores) of deep-sea shrimp, an autogenic system in which the organism possesses the substrates and enzymes to produce light. Through the integration of transcriptomics, in situ hybridization and immunohistochemistry we find evidence for the expression of opsins and phototransduction genes known to play a role in light detection in most animals. Subsequent shipboard light exposure experiments showed ultrastructural changes in the photophore similar to those seen in crustacean eyes, providing further evidence that photophores are light sensitive. In many deep-sea species, it has long been documented that photophores emit light to aid in counterillumination – a dynamic form of camouflage that requires adjusting the organ’s light intensity to “hide” their silhouettes from predators below. However, it remains a mystery how animals fine-tune their photophore luminescence to match the intensity of downwelling light. Photophore photosensitivity allows us to reconsider the organ’s role in counterillumination - not only in light emission but also light detection and regulation.
Privacy-preserving distributed learning of radiomics to predict overall survival and HPV status in head and neck cancer
Authors: Bogowicz Marta , Jochems Arthur , Deist Timo M. , Tanadini-Lang Stephanie , Huang Shao Hui , Chan Biu , Waldron John N. , Bratman Scott , O’Sullivan Brian , Riesterer Oliver , Studer Gabriela , Unkelbach Jan , Barakat Samir , Brakenhoff Ruud H. , Nauta Irene , Gazzani Silvia E. , Calareso Giuseppina , Scheckenbach Kathrin , Hoebers Frank , Wesseling Frederik W. R. , Keek Simon , Sanduleanu Sebastian , Leijenaar Ralph T. H. , Vergeer Marije R. , Leemans C. René , Terhaard Chris H. J. , van den Brekel Michiel W. M. , Hamming-Vrieze Olga , van der Heijden Martijn A. , Elhalawani Hesham M. , Fuller Clifton D. , Guckenberger Matthias , Lambin Philippe 
Published: March 2020

AbstractA major challenge in radiomics is assembling data from multiple centers. Sharing data between hospitals is restricted by legal and ethical regulations. Distributed learning is a technique, enabling training models on multicenter data without data leaving the hospitals (“privacy-preserving” distributed learning). This study tested feasibility of distributed learning of radiomics data for prediction of two year overall survival and HPV status in head and neck cancer (HNC) patients. Pretreatment CT images were collected from 1174 HNC patients in 6 different cohorts. 981 radiomic features were extracted using Z-Rad software implementation. Hierarchical clustering was performed to preselect features. Classification was done using logistic regression. In the validation dataset, the receiver operating characteristics (ROC) were compared between the models trained in the centralized and distributed manner. No difference in ROC was observed with respect to feature selection. The logistic regression coefficients were identical between the methods (absolute difference <10−7). In comparison of the full workflow (feature selection and classification), no significant difference in ROC was found between centralized and distributed models for both studied endpoints (DeLong p > 0.05). In conclusion, both feature selection and classification are feasible in a distributed manner using radiomics data, which opens new possibility for training more reliable radiomics models.
Impact of indoor residual spraying with pirimiphos-methyl (Actellic 300CS) on entomological indicators of transmission and malaria case burden in Migori County, western Kenya
Authors: Abong’o Bernard , Gimnig John E. , Torr Stephen J. , Longman Bradley , Omoke Diana , Muchoki Margaret , ter Kuile Feiko , Ochomo Eric , Munga Stephen , Samuels Aaron M. , Njagi Kiambo , Maas James , Perry Robert T. , Fornadel Christen , Donnelly Martin J. , Oxborough Richard M. 
Published: March 2020

AbstractIndoor residual spraying (IRS) of insecticides is a major vector control strategy for malaria prevention. We evaluated the impact of a single round of IRS with the organophosphate, pirimiphos-methyl (Actellic 300CS), on entomological and parasitological parameters of malaria in Migori County, western Kenya in 2017, in an area where primary vectors are resistant to pyrethroids but susceptible to the IRS compound. Entomological monitoring was conducted by indoor CDC light trap, pyrethrum spray catches (PSC) and human landing collection (HLC) before and after IRS. The residual effect of the insecticide was assessed monthly by exposing susceptible An. gambiae s.s. Kisumu strain to sprayed surfaces in cone assays and measuring mortality at 24 hours. Malaria case burden data were extracted from laboratory records of four health facilities within the sprayed area and two adjacent unsprayed areas. IRS was associated with reductions in An. funestus numbers in the intervention areas compared to non-intervention areas by 88% with light traps (risk ratio [RR] 0.12, 95% CI 0.07–0.21, p < 0.001) and 93% with PSC collections (RR = 0.07, 0.03–0.17, p < 0.001). The corresponding reductions in the numbers of An. arabiensis collected by PSC were 69% in the intervention compared to the non-intervention areas (RR = 0.31, 0.14–0.68, p = 0.006), but there was no significant difference with light traps (RR = 0.45, 0.21–0.96, p = 0.05). Before IRS, An. funestus accounted for over 80% of Anopheles mosquitoes collected by light trap and PSC in all sites. After IRS, An. arabiensis accounted for 86% of Anopheles collected by PSC and 66% by CDC light trap in the sprayed sites while the proportion in non-intervention sites remained unchanged. No sporozoite infections were detected in intervention areas after IRS and biting rates by An. funestus were reduced to near zero. Anopheles funestus and An. arabiensis were fully susceptible to pirimiphos-methyl and resistant to pyrethroids. The residual effect of Actellic 300CS lasted ten months on mud and concrete walls. Malaria case counts among febrile patients within IRS areas was lower post- compared to pre-IRS by 44%, 65% and 47% in Rongo, Uriri and Nyatike health facilities respectively. A single application of IRS with Actellic 300CS in Migori County provided ten months protection and resulted in the near elimination of the primary malaria vector An. funestus and a corresponding reduction of malaria case count among out-patients. The impact was less on An. arabiensis, most likely due to their exophilic nature.
Altered Adhesion and Migration of Human Mesenchymal Stromal Cells under Febrile Temperature Stress Involves NF-κβ Pathway
Authors: Sen Ankita , Ta Malancha 
Published: March 2020

AbstractMesenchymal stromal cells (MSCs) are clinically beneficial for regenerative treatment of chronic inflammation and autoimmune disorders. However, to attain maximum efficacy from the transplanted MSCs, evaluation of its interaction with the microenvironment, becomes critical. Fever being an important hallmark of inflammation, we investigated the effect of febrile temperature stress on adhesion and migration of umbilical cord-derived MSCs. 40 °C-exposure altered cellular morphology with significant cell flattening, delayed cell-matrix de-adhesion response and slower migration of MSCs, accompanied by suppressed directionality ratio and cell trajectory. Corresponding to the observed changes, mRNA expression of extracellular matrix genes like COLs and VTN were upregulated, while matrix metalloproteinase MMP-1, showed a significant downregulation. NF-κβ pathway inhibition at 40 °C, led to reversal of gene expression pattern, cell spreading, de-adhesion dynamics and migration rate. Independent knockdown of p65 and p53 at 40 °C indicated inhibitory role of p65/p53/p21 axis in regulation of MMP-1 expression. P21 inhibits JNK activity, and JNK pathway inhibition at 40 °C resulted in further downregulation of MMP-1. Hence, our study provides the first evidence of cell migration getting adversely affected in MSCs under elevated temperature stress due to an inverse relationship between p65/p53/p21 and MMP1 with a possible involvement of the JNK pathway.
Predictive factors for bacteremia in febrile infants with urinary tract infection
Authors: Yoon Seo Hee , Shin HyunDo , Lee Keum Hwa , Kim Moon Kyu , Kim Dong Soo , Ahn Jong Gyun , Shin Jae Il 
Published: March 2020

AbstractThis study aimed to investigate the predictive factors of concomitant bacteremia occurring in febrile infants who initially presented with pyuria and fever, and were subsequently diagnosed with culture-proven urinary tract infection (UTI). We conducted a retrospective cohort study for January 2010–October 2018 that included infants younger than six months with febrile UTI at a tertiary hospital. The study included 463 patients, of whom 34 had a concomitant bacteremic UTI. Compared to those in the non-bacteremic urinary tract infection (UTI) group, the bacteremic UTI group had a lower mean age; higher levels of C-reactive protein (CRP), delta neutrophil index (DNI, reflects the fraction of immature granulocytes) and blood urea nitrogen (BUN); lower levels of hemoglobin (Hb) and albumin; and a lower platelet count. Vesicoureteral reflux (VUR) was detected nearly twice as often in patients with bacteremic UTI compared to those with non-bacteremic UTI (59.3% vs. 30.6%; P = 0.003). Univariate logistic analyses showed that age ≤90 days; higher DNI, CRP, and creatinine levels; lower Hb and albumin levels; and the presence of VUR were predictors for bacteremic UTI. On multivariate logistic regression analysis, age ≤90 days, higher DNI and CRP levels, and the presence of VUR were independent predictors of bacteremic UTI. The area under the receiver operating characteristic curve of the multivariate model was 0.859 (95% CI, 0.779–0.939; P < 0.001). Age ≤90 days, higher DNI and CRP values may help predict bacteremia of febrile infants younger than 6 months with UTI. Vesicoureteral reflux imaging is also recommended in infants with bacteremic UTI to evaluate VUR.
The Prognostic Role of Procalcitonin in Critically Ill Patients Admitted in a Medical Stepdown Unit: A Retrospective Cohort Study
Authors: Zaccone Vincenzo , Falsetti Lorenzo , Nitti Cinzia , Gentili Tamira , Marchetti Annalisa , Piersantelli Maria Novella , Sampaolesi Mattia , Riccomi Francesca , Raponi Alessia , Salvi Aldo 
Published: March 2020

AbstractProcalcitonin (PCT) is a a marker of bacterial infection. Its prognostic role in the critically-ill patient, however, is still object of debate. Aim of this study was to evaluate the capacity of admission PCT (aPCT) in assessing the prognosis of the critically-ill patient regardless the presence of bacterial infection. A single-cohort, single-center retrospective study was performed evaluating critically-ill patients admitted to a stepdown care unit. Age, sex, Simplified Acute Physiology Score II (SAPS-II), shock, troponin-I, aPCT, serum creatinine, cultures and clinical endpoints (in-hospital mortality or Intensive Care Unit (ICU) transfer) were collected. Time free from adverse event (TF-AE) was defined as the time between hospitalization and occurrence of one of the clinical endpoints, and calculated with Kaplan-Meier curves. We engineered a new predictive model (POCS) adopting aPCT, age and shock.We enrolled 1063 subjects: 450 reached the composite outcome of death or ICU transfer. aPCT was significantly higher in this group, where it predicted TF-AE both in septic and non-septic patients. aPCT and POCS showed a good prognostic performance in the whole sample, both in septic and non-septic patients. aPCT showed a good prognostic accuracy, adding informations on the rapidity of clinical deterioration. POCS model reached a performance similar to SAPS-II.