bluuebunny/crossref_metadata_2025_split huggingface dataset:
Baseline microvessel density predicts response to neoadjuvant bevacizumab treatment of locally advanced breast cancer
Authors: Krüger Kristi , Silwal-Pandit Laxmi , Wik Elisabeth , Straume Oddbjørn , Stefansson Ingunn M. , Borgen Elin , Garred Øystein , Naume Bjørn , Engebraaten Olav , Akslen Lars A. 
Published: February 2021

AbstractA subset of breast cancer patients benefits from preoperative bevacizumab and chemotherapy, but validated predictive biomarkers are lacking. Here, we aimed to evaluate tissue-based angiogenesis markers for potential predictive value regarding response to neoadjuvant bevacizumab treatment in breast cancer. In this randomized 1:1 phase II clinical trial, 132 patients with large or locally advanced HER2-negative tumors received chemotherapy ± bevacizumab. Dual Factor VIII/Ki-67 immunohistochemical staining was performed on core needle biopsies at baseline and week 12. Microvessel density (MVD), proliferative microvessel density (pMVD; Factor VIII/Ki-67 co-expression), glomeruloid microvascular proliferation (GMP), and a gene expression angiogenesis signature score, were studied in relation to pathologic complete response (pCR), clinico-pathologic features and intrinsic molecular subtype. We found that high baseline MVD (by median) significantly predicted pCR in the bevacizumab-arm (odds ratio 4.9, P = 0.012). High pMVD, presence of GMP, and the angiogenesis signature score did not predict pCR, but were associated with basal-like (P ≤ 0.009) and triple negative phenotypes (P ≤ 0.041). pMVD and GMP did also associate with high-grade tumors (P ≤ 0.048). To conclude, high baseline MVD significantly predicted response to bevacizumab treatment. In contrast, pMVD, GMP, and the angiogenesis signature score, did not predict response, but associated with aggressive tumor features, including basal-like and triple-negative phenotypes.
Physiological and molecular responses of lobe coral indicate nearshore adaptations to anthropogenic stressors
Authors: Tisthammer Kaho H. , Timmins-Schiffman Emma , Seneca Francois O. , Nunn Brook L. , Richmond Robert H. 
Published: February 2021

AbstractCorals in nearshore marine environments are increasingly exposed to reduced water quality, which is the primary local threat to Hawaiian coral reefs. It is unclear if corals surviving in such conditions have adapted to withstand sedimentation, pollutants, and other environmental stressors. Lobe coral populations from Maunalua Bay, Hawaii showed clear genetic differentiation between the 'polluted, high-stress' nearshore site and the 'less polluted, lower-stress' offshore site. To understand the driving force of the observed genetic partitioning, reciprocal transplant and common-garden experiments were conducted to assess phenotypic differences between these two populations. Physiological responses differed significantly between the populations, revealing more stress-resilient traits in the nearshore corals. Changes in protein profiles highlighted the inherent differences in the cellular metabolic processes and activities between the two; nearshore corals did not significantly alter their proteome between the sites, while offshore corals responded to nearshore transplantation with increased abundances of proteins associated with detoxification, antioxidant defense, and regulation of cellular metabolic processes. The response differences across multiple phenotypes between the populations suggest local adaptation of nearshore corals to reduced water quality. Our results provide insight into coral’s adaptive potential and its underlying processes, and reveal potential protein biomarkers that could be used to predict resiliency.
Voluntary intake of psychoactive substances is regulated by the dopamine receptor Dop1R1 in Drosophila
Authors: Kanno Mai , Hiramatsu Shun , Kondo Shu , Tanimoto Hiromu , Ichinose Toshiharu 
Published: February 2021

AbstractDysregulated motivation to consume psychoactive substances leads to addictive behaviors that often result in serious health consequences. Understanding the neuronal mechanisms that drive drug consumption is crucial for developing new therapeutic strategies. The fruit fly Drosophila melanogaster offers a unique opportunity to approach this problem with a battery of sophisticated neurogenetic tools available, but how they consume these drugs remains largely unknown. Here, we examined drug self-administration behavior of Drosophila and the underlying neuronal mechanisms. We measured the preference of flies for five different psychoactive substances using a two-choice feeding assay and monitored its long-term changes. We found that flies show acute preference for ethanol and methamphetamine, but not for cocaine, caffeine or morphine. Repeated intake of ethanol, but not methamphetamine, increased over time. Preference for methamphetamine and the long-term escalation of ethanol preference required the dopamine receptor Dop1R1 in the mushroom body. The protein level of Dop1R1 increased after repeated intake of ethanol, but not methamphetamine, which correlates with the acquired preference. Genetic overexpression of Dop1R1 enhanced ethanol preference. These results reveal a striking diversity of response to individual drugs in the fly and the role of dopamine signaling and its plastic changes in controlling voluntary intake of drugs.
Effect of tamoxifen with or without gonadotropin-releasing hormone analog on DXA values in women with breast cancer
Authors: Kim Eun Heui , Jeon Yun Kyung , Pak Kyoungjune , Kang Taewoo , Kim Kyung-Eun , Kim Seong-Jang , Kim In-Joo , Kim Keunyoung 
Published: February 2021

AbstractThe purpose of this study was to compare the changes in DXA values including trabecular bone score (TBS) and bone mineral density (BMD) of lumbar spine (LS) and femur according to the hormone therapies including tamoxifen (TMXF) treatment with or without gonadotropin releasing hormone analog (GnRH analog) in women with breast cancer. We enrolled 119 women with breast cancer who had undergone breast-conserving surgery or mastectomy followed by TMXF treatment for postmenopausal women (TMXF group, n = 63, 52.9%) or by combination therapy of TMXF combined with GnRH analog for premenopausal women (TMXF + GnRH group, n = 56, 47.1%) from December 2013 to December 2017. The median follow-up period was 13 months (interquartile range [IQR], 12.0–14.75) for TMXF group and 13.5 months (IQR, 12.00–16.00) for TMXF + GnRH group, respectively. Patients did not receive bone-modifying therapy. The baseline dual-energy X-ray absorptiometry (DXA) scan before breast cancer surgery and follow-up DXA during hormone therapy. Comparing the first and follow-up DXA results, BMD in LS were significantly decreased in both TMXF (P < 0.001, mean difference: − 0.06) and TMXF + GnRH (P < 0.001, mean difference: − 0.09) groups. BMD values of femoral neck (P = 0.0011, mean difference: − 0.01) and total femur (P < 0.001, mean difference: − 0.03) was significantly changed between the baseline and follow-up DXA in TMXF + RnRH group. In the TMX group, a significant changed occurred in the BMD in total femur (P < 0.001, mean difference: − 0.030) but not the BMD of femoral neck (P = 0.095, mean difference: − 0.007). Regarding TBS, no significant change was found in the TMXF (P = 0.574, mean difference: − 0.004) group, whereas there was a significant decrease in TBS in the TMXF + GnRH (P < 0.001, mean difference: − 0.02) group during follow-up. TBS is more sensitive in reflecting the bone microarchitecture changes by TMXF or GnRH agonist in breast cancer patients than BMD. This finding demonstrates that TBS can be a useful parameter to detect bone microarchitectural changes in clinical applications.
Automated diagnostic support system with deep learning algorithms for distinction of Philadelphia chromosome-negative myeloproliferative neoplasms using peripheral blood specimen
Authors: Kimura Konobu , Ai Tomohiko , Horiuchi Yuki , Matsuzaki Akihiko , Nishibe Kumiko , Marutani Setsuko , Saito Kaori , Kaniyu Kimiko , Takehara Ikki , Uchihashi Kinya , Ohsaka Akimichi , Tabe Yoko 
Published: February 2021

AbstractPhiladelphia chromosome-negative myeloproliferative neoplasms (Ph-negative MPNs) such as polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis are characterized by abnormal proliferation of mature bone marrow cell lineages. Since various non-hematologic disorders can also cause leukocytosis, thrombocytosis and polycythemia, the detection of abnormal peripheral blood cells is essential for the diagnostic screening of Ph-negative MPNs. We sought to develop an automated diagnostic support system of Ph-negative MPNs. Our strategy was to combine the complete blood cell count and research parameters obtained by an automated hematology analyzer (Sysmex XN-9000) with morphological parameters that were extracted using a convolutional neural network deep learning system equipped with an Extreme Gradient Boosting (XGBoost)-based decision-making algorithm. The developed system showed promising performance in the differentiation of PV, ET, and MF with high accuracy when compared with those of the human diagnoses, namely: > 90% sensitivity and > 90% specificity. The calculated area under the curve of the ROC curves were 0.990, 0.967, and 0.974 for PV, ET, MF, respectively. This study is a step toward establishing a universal automated diagnostic system for all types of hematology disorders.
Dependence of the damage in optical metal/dielectric coatings on the energy of ions in irradiation experiments for space qualification
Authors: Pelizzo Maria G. , Corso Alain J. , Santi Giovanni , Hübner René , Garoli Denis , Doyle Dominic , Lubin Philip , Cohen Alexander N. , Erlikhman Jacob , Favaro Giulio , Bazzan Marco , Drobny Jon , Curreli Davide , Umansky Maxim 
Published: February 2021

AbstractTerrestrial accelerator facilities can generate ion beams which enable the testing of the resistance of materials and thin film coatings to be used in the space environment. In this work, a $$\hbox {TiO}_2$$

TiO
2

/Al bi-layer coating has been irradiated with a $$\hbox {He}^+$$

He
+

beam at three different energies. The same flux and dose have been used in order to investigate the damage dependence on the energy. The energies were selected to be in the range 4–100 keV, in order to consider those associated to the quiet solar wind and to the particles present in the near-Earth space environment. The optical, morphological and structural modifications have been investigated by using various techniques. Surprisingly, the most damaged sample is the one irradiated at the intermediate energy, which, on the other hand, corresponds to the case in which the interface between the two layers is more stressed. Results demonstrate that ion energies for irradiation tests must be carefully selected to properly qualify space components.
Observation of terahertz coherent edge radiation amplified by infrared free-electron laser oscillations
Authors: Sei Norihiro , Sakai Takeshi , Hayakawa Yasushi , Sumitomo Yoske , Nogami Kyoko , Tanaka Toshinari , Hayakawa Ken 
Published: February 2021

AbstractA coupling device, which can extract coherent edge radiation (CER) from an optical cavity for a free-electron laser (FEL) without damaging the FEL due to diffraction loss, was developed at Nihon University. We successfully observed the CER beam with a power of 1 mW or more in the terahertz range during FEL oscillation. It is revealed that the CER power changed with the detuning of the optical cavity and the dependence of the CER power on the detuning length differs from that of the FEL power. The measured CER spectra indicate that the longitudinal electron distribution in a bunch is modulated by the FEL oscillation with a period corresponding to the FEL slippage length. We herein report the characteristics of the CER with FEL oscillation in detail. These results demonstrate that the CER is excellent tool to reveal the overall effect of FEL interaction on electron distribution in a bunch.
Rapid profiling of drug-resistant bacteria using DNA-binding dyes and a nanopore-based DNA sequencer
Authors: Ohno Ayumu , Umezawa Kazuo , Asai Satomi , Kryukov Kirill , Nakagawa So , Miyachi Hayato , Imanishi Tadashi 
Published: February 2021

AbstractSpread of drug-resistant bacteria is a serious problem worldwide. We thus designed a new sequence-based protocol that can quickly identify bacterial compositions of clinical samples and their drug-resistance profiles simultaneously. Here we utilized propidium monoazide (PMA) that prohibits DNA amplifications from dead bacteria, and subjected the original and antibiotics-treated samples to 16S rRNA metagenome sequencing. We tested our protocol on bacterial mixtures, and observed that sequencing reads derived from drug-resistant bacteria were significantly increased compared with those from drug-sensitive bacteria when samples were treated by antibiotics. Our protocol is scalable and will be useful for quickly profiling drug-resistant bacteria.
A general framework for automatic closed-loop control of bladder voiding induced by intraspinal microstimulation in rats
Authors: Yousefpour Abolhasan , Erfanian Abbas 
Published: February 2021

AbstractIndividuals with spinal cord injury or neurological disorders have problems in voiding function due to the dyssynergic contraction of the urethral sphincter. Here, we introduce a closed-loop control of intraspinal microstimulation (ISMS) for efficient bladder voiding. The strategy is based on asynchronous two-electrode ISMS with combined pulse-amplitude and pulse-frequency modulation without requiring rhizotomy, neurotomy, or high-frequency blocking. Intermittent stimulation is alternately applied to the two electrodes that are implanted in the S2 lateral ventral horn and S1 dorsal gray commissure, to excite the bladder motoneurons and to inhibit the urethral sphincter motoneurons. Asynchronous stimulation would lead to reduce the net electric field and to maximize the selective stimulation. The proposed closed-loop system attains a highly voiding efficiency of 77.2–100%, with an average of 91.28 ± 8.4%. This work represents a promising approach to the development of a natural and robust motor neuroprosthesis device for restoring bladder functions.
Selective endocytosis of recombinant human BMPs through cell surface heparan sulfate proteoglycans in CHO cells: BMP-2 and BMP-7
Authors: Kim Mi Gyeom , Kim Che Lin , Kim Young Sik , Jang Ju Woong , Lee Gyun Min 
Published: February 2021

AbstractCell surface heparan sulfate proteoglycan (HSPG)-mediated endocytosis results in poor yields of recombinant human bone morphogenetic proteins (rhBMPs) from CHO cell cultures. Upon incubation of rhBMP-2 and rhBMP-7 with CHO cells at 37 °C, both rhBMP-2 and rhBMP-7 bound to the cell surface HSPGs in CHO cells, but only rhBMP-2 was actively internalized into CHO cells. Cell surface HSPGs were found to serve as the main receptor for rhBMP-2 internalization. It was also found that the cell surface HSPG-mediated endocytosis of rhBMP-2 occurred through both the clathrin- and caveolin-dependent pathways. Blockage of rhBMP-2 internalization by the addition of structural analogs of HSPGs such as dextran sulfate (DS) and heparin dramatically increased rhBMP-2 production in recombinant CHO (rCHO) cell cultures. Compared to the control cultures, addition of DS (1.0 g/L) and heparin (0.2 g/L) resulted in a 22.0- and 19.0-fold increase in the maximum rhBMP-2 concentration, respectively. In contrast, the production of rhBMP-7, which was not internalized into the rCHO cells, did not dramatically increase upon addition of DS and heparin. Taken together, rhBMPs have a different fate in terms of HSPG-mediated internalization in CHO cells. HSPG-mediated endocytosis of each rhBMP should be understood individually to increase the rhBMP yield in rCHO cell cultures.
Describing variability in pig genes involved in coronavirus infections for a One Health perspective in conservation of animal genetic resources
Authors: Bovo Samuele , Schiavo Giuseppina , Ribani Anisa , Utzeri Valerio J. , Taurisano Valeria , Ballan Mohamad , Muñoz Maria , Alves Estefania , Araujo Jose P. , Bozzi Riccardo , Charneca Rui , Di Palma Federica , Djurkin Kušec Ivona , Etherington Graham , Fernandez Ana I. , García Fabián , García-Casco Juan , Karolyi Danijel , Gallo Maurizio , Martins José Manuel , Mercat Marie-José , Núñez Yolanda , Quintanilla Raquel , Radović Čedomir , Razmaite Violeta , Riquet Juliette , Savić Radomir , Škrlep Martin , Usai Graziano , Zimmer Christoph , Ovilo Cristina , Fontanesi Luca 
Published: February 2021

AbstractCoronaviruses silently circulate in human and animal populations, causing mild to severe diseases. Therefore, livestock are important components of a “One Health” perspective aimed to control these viral infections. However, at present there is no example that considers pig genetic resources in this context. In this study, we investigated the variability of four genes (ACE2, ANPEP and DPP4 encoding for host receptors of the viral spike proteins and TMPRSS2 encoding for a host proteinase) in 23 European (19 autochthonous and three commercial breeds and one wild boar population) and two Asian Sus scrofa populations. A total of 2229 variants were identified in the four candidate genes: 26% of them were not previously described; 29 variants affected the protein sequence and might potentially interact with the infection mechanisms. The results coming from this work are a first step towards a “One Health” perspective that should consider conservation programs of pig genetic resources with twofold objectives: (i) genetic resources could be reservoirs of host gene variability useful to design selection programs to increase resistance to coronaviruses; (ii) the described variability in genes involved in coronavirus infections across many different pig populations might be part of a risk assessment including pig genetic resources.
Dose-related effects of extracorporeal shock waves on orthodontic tooth movement in rabbits
Authors: Demir Onur , Arici Nursel 
Published: February 2021

AbstractThe purpose of this animal study is to investigate the quantitative effects of extracorporeal shock waves applied at two different impulses and with two different applicators on orthodontic tooth movement. Thirty-five New Zealand rabbits were randomly divided into five groups (n = 7): the four experimental extracorporeal shock wave groups—focused/500 impulses, focused/1000 impulses, unfocused/500 impulses, and unfocused/1000 impulses—and the control group. Orthodontic tooth movement was achieved by application of reciprocal force between two maxillary incisors. In the experimental groups, animals received 500 or 1000 impulses of extracorporeal shock waves at 0.19 mJ/mm2 with focused or unfocused applicators depending on the group to which they belonged. These experiments were conducted on days 0, 7, and 14. Orthodontic tooth movement was measured with 0.01 mm accuracy at one-week intervals. On days 7 and 21, the bone-specific alkaline phosphatase levels were measured from blood samples. After 21 days, the animals were sacrificed and the area between the two maxillary incisors was stereologically examined. Orthodontic tooth movement in the focused/500 impulses and focused/1000 impulses groups was significantly increased compared to the control group. A significant difference in bone-specific alkaline phosphatase levels between the unfocused/500 impulses and control groups was found at 21st day. Stereological analysis showed that there were significant increases of the formation of new bone, connective tissue, and vessels in the experimental groups. The application of extracorporeal shock waves, especially with a focused applicator, could accelerate orthodontic tooth movement.
Identification of epigenetic memory candidates associated with gestational age at birth through analysis of methylome and transcriptional data
Authors: Kashima Kohei , Kawai Tomoko , Nishimura Riki , Shiwa Yuh , Urayama Kevin Y. , Kamura Hiromi , Takeda Kazue , Aoto Saki , Ito Atsushi , Matsubara Keiko , Nagamatsu Takeshi , Fujii Tomoyuki , Omori Isaku , Shimizu Mitsumasa , Hyodo Hironobu , Kugu Koji , Matsumoto Kenji , Shimizu Atsushi , Oka Akira , Mizuguchi Masashi , Nakabayashi Kazuhiko , Hata Kenichiro , Takahashi Naoto 
Published: February 2021

AbstractPreterm birth is known to be associated with chronic disease risk in adulthood whereby epigenetic memory may play a mechanistic role in disease susceptibility. Gestational age (GA) is the most important prognostic factor for preterm infants, and numerous DNA methylation alterations associated with GA have been revealed by epigenome-wide association studies. However, in human preterm infants, whether the methylation changes relate to transcription in the fetal state and persist after birth remains to be elucidated. Here, we identified 461 transcripts associated with GA (range 23–41 weeks) and 2093 candidate CpG sites for GA-involved epigenetic memory through analysis of methylome (110 cord blood and 47 postnatal blood) and transcriptional data (55 cord blood). Moreover, we discovered the trends of chromatin state, such as polycomb-binding, among these candidate sites. Fifty-four memory candidate sites showed correlation between methylation and transcription, and the representative corresponding gene wasUCN, which encodes urocortin.
Machine learning prediction models for prognosis of critically ill patients after open-heart surgery
Authors: Zhong Zhihua , Yuan Xin , Liu Shizhen , Yang Yuer , Liu Fanna 
Published: February 2021

AbstractWe aimed to build up multiple machine learning models to predict 30-days mortality, and 3 complications including septic shock, thrombocytopenia, and liver dysfunction after open-heart surgery. Patients who underwent coronary artery bypass surgery, aortic valve replacement, or other heart-related surgeries between 2001 and 2012 were extracted from MIMIC-III databases. Extreme gradient boosting, random forest, artificial neural network, and logistic regression were employed to build models by utilizing fivefold cross-validation and grid search. Receiver operating characteristic curve, area under curve (AUC), decision curve analysis, test accuracy, F1 score, precision, and recall were applied to access the performance. Among 6844 patients enrolled in this study, 215 patients (3.1%) died within 30 days after surgery, part of patients appeared liver dysfunction (248; 3.6%), septic shock (32; 0.5%), and thrombocytopenia (202; 2.9%). XGBoost, selected to be our final model, achieved the best performance with highest AUC and F1 score. AUC and F1 score of XGBoost for 4 outcomes: 0.88 and 0.58 for 30-days mortality, 0.98 and 0.70 for septic shock, 0.88 and 0.55 for thrombocytopenia, 0.89 and 0.40 for liver dysfunction. We developed a promising model, presented as software, to realize monitoring for patients in ICU and to improve prognosis.