bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modern Meteoric 36Cl Deposition in the Atacama Desert, Chile
Authors: Wang Fan , Michalski Greg 
Published: October 2020

AbstractModern atmospheric deposition along a west‐east transect in the Atacama Desert, Chile, was collected to constrain the meteoric 36Cl/Cl ratio and 36Cl deposition flux. The 36Cl deposition flux had a threefold change, from 3.62(±0.18) to 11.6(±0.2) atoms m−2 s−1, going from the coast to the high Andes. The 36Cl deposition was mainly as dry deposition, and the magnitude and differences between sites were attributed to stratosphere‐troposphere transport and chloride deficits by acid displacement, respectively. The meteoric 36Cl/Cl ratios varied greatly from 31.5(±1.1) × 10−15 to 247(±10) × 10−15, which was attributed to local inputs of oceanic chloride near the coast or chloride minerals entrained from nearby salt playas. This study presented refined estimates of the 36Cl deposition flux and meteoric 36Cl/Cl ratio in a desert region in southern tropical zone. The data set will provide a baseline for using natural 36Cl abundances to date salt accumulation in the Atacama.
Ventral pallidal GABAergic neurons control wakefulness associated with motivation through the ventral tegmental pathway
Authors: Li Ya-Dong , Luo Yan-Jia , Xu Wei , Ge Jing , Cherasse Yoan , Wang Yi-Qun , Lazarus Michael , Qu Wei-Min , Huang Zhi-Li 
Published: October 2020

AbstractThe ventral pallidum (VP) regulates motivation, drug addiction, and several behaviors that rely on heightened arousal. However, the role and underlying neural circuits of the VP in the control of wakefulness remain poorly understood. In the present study, we sought to elucidate the specific role of VP GABAergic neurons in controlling sleep–wake behaviors in mice. Fiber photometry revealed that the population activity of VP GABAergic neurons was increased during physiological transitions from non-rapid eye movement (non-REM, NREM) sleep to either wakefulness or REM sleep. Moreover, chemogenetic and optogenetic manipulations were leveraged to investigate a potential causal role of VP GABAergic neurons in initiating and/or maintaining arousal. In vivo optogenetic stimulation of VP GABAergic neurons innervating the ventral tegmental area (VTA) strongly promoted arousal via disinhibition of VTA dopaminergic neurons. Functional in vitro mapping revealed that VP GABAergic neurons, in principle, inhibited VTA GABAergic neurons but also inhibited VTA dopaminergic neurons. In addition, optogenetic stimulation of terminals of VP GABAergic neurons revealed that they promoted arousal by innervating the lateral hypothalamus, but not the mediodorsal thalamus or lateral habenula. The increased wakefulness chemogenetically evoked by VP GABAergic neuronal activation was completely abolished by pretreatment with dopaminergic D1 and D2/D3 receptor antagonists. Furthermore, activation of VP GABAergic neurons increased exploration time in both the open-field and light–dark box tests but did not modulate depression-like behaviors or food intake. Finally, chemogenetic inhibition of VP GABAergic neurons decreased arousal. Taken together, our findings indicate that VP GABAergic neurons are essential for arousal related to motivation.
Prognostic significance of pre-treatment neutrophil-to-lymphocyte ratio (NLR) in patients with oropharyngeal cancer treated with radiotherapy
Authors: Ng Sweet Ping , Bahig Houda , Jethanandani Amit , Sturgis Erich M. , Johnson Faye M. , Elgohari Baher , Gunn G. Brandon , Ferrarotto Renata , Phan Jack , Rosenthal David I. , Frank Steven J. , Fuller Clifton D. , Garden Adam S. 
Published: October 2020

Abstract
Background
This study aimed to evaluate the prognostic value of pre-treatment NLR in patients with oropharyngeal cancer.

Methods
Patients who completed definitive radiotherapy (RT) for oropharyngeal cancer and had blood counts taken pre-RT from 2002 to 2013 were included. NLR was calculated as total neutrophil/lymphocytes. Survival rates were estimated using the Kaplan–Meier method. Univariable and multivariable analyses were conducted with linear and Cox regression methods. NLR was analysed posteriori and dichotomised on the discovered median.

Results
Eight hundred and forty-eight patients were analysed. The median pre-RT NLR was 3. Patients with NLR of <3 had improved overall survival (OS) than those with NLR ≥ 3 (5-year OS 85 vs 74%, p < 0.0001). OS differences remained significant when stratified according to HPV status (HPV-positive p = 0.011; HPV-negative p = 0.003). Freedom from any recurrence (FFR), locoregional control (LRC) and freedom of distant recurrence (FDR) were better in those with NLR < 3. The negative impact of elevated pre-RT NLR on OS (HR = 1.64, p = 0.001), FFR (HR = 1.6, p = 0.006) and LRC (HR = 1.8, p = 0.005) remained significant on multivariable analysis.

Conclusions
Pre-RT NLR is an independent prognostic factor in patients with oropharyngeal cancer regardless of HPV status. Patients with lower NLR had more favourable OS and disease control.
Long non-coding RNA CASC9 promotes gefitinib resistance in NSCLC by epigenetic repression of DUSP1
Authors: Chen Zhenyao , Chen Qinnan , Cheng Zhixiang , Gu Jingyao , Feng Wenyan , Lei Tianyao , Huang Jiali , Pu Jiaze , Chen Xin , Wang Zhaoxia 
Published: October 2020

AbstractResistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), such as gefitinib, has greatly affected clinical outcomes in non-small cell lung cancer (NSCLC) patients. The long noncoding RNAs (lncRNAs) are known to regulate tumorigenesis and cancer progression, but their contributions to NSCLC gefitinib resistance remain poorly understood. In this study, by analyzing the differentially expressed lncRNAs in gefitinib-resistant cells and gefitinib-sensitive cells in the National Institute of Health GEO dataset, we found that lncRNA CASC9 expression was upregulated, and this was also verified in resistant tissues. Gain and loss of function studies showed that CASC9 inhibition restored gefitinib sensitivity both in vitro and in vivo, whereas CASC9 overexpression promoted gefitinib resistance. Mechanistically, CASC9 repressed the tumor suppressor DUSP1 by recruiting histone methyltransferase EZH2, thereby increasing the resistance to gefitinib. Furthermore, ectopic expression of DUSP1 increased gefitinib sensitivity by inactivating the ERK pathway. Our results highlight the essential role of CASC9 in gefitinib resistance, suggesting that the CASC9/EZH2/DUSP1 axis might be a novel target for overcoming EGFR-TKI resistance in NSCLC.
Novel copper complex CTB regulates methionine cycle induced TERT hypomethylation to promote HCC cells senescence via mitochondrial SLC25A26
Authors: Jin Chun , Li Yujia , Su Ying , Guo Zijian , Wang Xiaoyong , Wang Shijun , Zhang Feng , Zhang Zili , Shao Jiangjuan , Zheng Shizhong 
Published: October 2020

AbstractRelated research has recognized the vital role of methionine cycle metabolism in cancers. However, the role and mechanism of methionine cycle metabolism in hepatocellular carcinoma are still unknown. In this study, we found that [Cu(ttpy-tpp)Br2]Br (Referred to as CTB) could induce hepatocellular carcinoma cells senescence, which is a new copper complex synthesized by our research group. Interestingly, CTB induces senescence by inhibiting the methionine cycle metabolism of HCC cells. Furthermore, the inhibitory effect of CTB on the methionine cycle depends on mitochondrial carrier protein SLC25A26, which was also required for CTB-induced HCC cells senescence. Importantly, we found that CTB-induced upregulation of SLC25A26 could cause abnormal methylation of TERT and inhibited TERT expression, which is considered to be an essential cause of cell senescence. The same results were also obtained in vivo, CTB inhibits the growth of subcutaneously implanted tumors in nude mice and promoted the expression of senescence markers in tumor tissues, and interference with SLC25A26 partially offset the antitumor effect of CTB.
Changes in patient subjective happiness and satisfaction with cataract surgery
Authors: Yotsukura Erisa , Ayaki Masahiko , Nezu Naohisa , Torii Hidemasa , Arai Hiroyuki , Sakatani Keiko , Tsubota Kazuo , Negishi Kazuno 
Published: October 2020

AbstractThe purpose of this study was to investigate the changes in patient subjective happiness and satisfaction with cataract surgery and evaluate the association between satisfaction and types of cataract. This study surveyed 247 participants (mean age, 67.9 years) and they completed questionnaires on their satisfaction with the surgery, the subjective happiness scale (SHS) and the Pittsburgh Sleep Quality Index (PSQI) before and after surgery. The SHS increased postoperatively from 4.6 ± 0.7 to 4.8 ± 0.7 (P = 0.007) and 83.4% of patients were satisfied with the surgical results and the average satisfaction score was 4.2 out of a possible 5.0. Multiple regression analysis showed that patient satisfaction was significantly associated with the postoperative SHS (β = 0.380; P < 0.001), the postoperative PSQI (β = −0.041; P = 0.035) and the presence of a posterior subcapsular cataract (PSC) (β = 0.277; P = 0.026). This study clarified that cataract surgery may improve both visual function and patient happiness and that patient satisfaction was affected by postoperative sleep quality and the disappearance of a PSC.
Vitality form expression in autism
Authors: Casartelli L. , Cesareo A. , Biffi E. , Campione G. C. , Villa L. , Molteni M. , Sinigaglia C. 
Published: October 2020

AbstractThe notion of “vitality form” has been coined by Daniel Stern to describe the basic features of action, which may reflect the mood or affective state of an agent. There is general consensus that vitality forms substantiate social interactions in children as well in adults. Previous studies have explored children with Autism Spectrum Disorder (ASD)’s ability in copying and recognizing the vitality forms of actions performed by others. In this paper we investigated, for the first time, how children with ASD express different vitality forms when acting themselves. We recorded the kinematics of ASD and typically developing (TD) children while performing three different types of action with two different vitality forms. There were two conditions. In the what condition we contrasted the three different types of action performed with a same vitality form, while in the how condition we contrasted the same type of action performed with two different vitality forms. The results showed a clear difference between ASD children and TD children in the how, but not in the what, condition. Indeed, while TD children distinguished the vitality forms to be expressed by mostly varying a specific spatiotemporal parameter (i.e. movement time), no significant variation in this parameter was found in ASD children. As they are not prone to express vitality forms as neurotypical individuals do, individuals with ASD’s interactions with neurotypical peers could therefore be difficult to achieve successfully, with cascading effects on their propensity to be tuned to their surrounding social world, or so we conjecture. If this conjecture would turn out to be correct, our findings could have promising implication for theoretical and clinical research in the context of ASD.
5-aminolevulinic acid-mediated photodynamic therapy can target aggressive adult T cell leukemia/lymphoma resistant to conventional chemotherapy
Authors: Sando Yasuhisa , Matsuoka Ken-ichi , Sumii Yuichi , Kondo Takumi , Ikegawa Shuntaro , Sugiura Hiroyuki , Nakamura Makoto , Iwamoto Miki , Meguri Yusuke , Asada Noboru , Ennishi Daisuke , Nishimori Hisakazu , Fujii Keiko , Fujii Nobuharu , Utsunomiya Atae , Oka Takashi , Maeda Yoshinobu 
Published: October 2020

AbstractPhotodynamic therapy (PDT) is an emerging treatment for various solid cancers. We recently reported that tumor cell lines and patient specimens from adult T cell leukemia/lymphoma (ATL) are susceptible to specific cell death by visible light exposure after a short-term culture with 5-aminolevulinic acid, indicating that extracorporeal photopheresis could eradicate hematological tumor cells circulating in peripheral blood. As a bridge from basic research to clinical trial of PDT for hematological malignancies, we here examined the efficacy of ALA-PDT on various lymphoid malignancies with circulating tumor cells in peripheral blood. We also examined the effects of ALA-PDT on tumor cells before and after conventional chemotherapy. With 16 primary blood samples from 13 patients, we demonstrated that PDT efficiently killed tumor cells without influencing normal lymphocytes in aggressive diseases such as acute ATL. Importantly, PDT could eradicate acute ATL cells remaining after standard chemotherapy or anti-CCR4 antibody, suggesting that PDT could work together with other conventional therapies in a complementary manner. The responses of PDT on indolent tumor cells were various but were clearly depending on accumulation of protoporphyrin IX, which indicates the possibility of biomarker-guided application of PDT. These findings provide important information for developing novel therapeutic strategy for hematological malignancies.
TAS0314, a novel multi-epitope long peptide vaccine, showed synergistic antitumor immunity with PD-1/PD-L1 blockade in HLA-A*2402 mice
Authors: Tanaka Yuki , Wada Hiroshi , Goto Risa , Osada Toshihiro , Yamamura Keisuke , Fukaya Satoshi , Shimizu Atsushi , Okubo Mitsuru , Minamiguchi Kazuhisa , Ikizawa Koichi , Sasaki Eiji , Utsugi Teruhiro 
Published: October 2020

AbstractCancer peptide vaccines are a promising cancer immunotherapy that can induce cancer-specific cytotoxic T lymphocytes (CTLs) in tumors. However, recent clinical trials of cancer vaccines have revealed that the efficacy of the vaccines is limited. Targeting single antigens and vaccination with short peptides are partly the cause of the poor clinical outcomes. We synthesized a novel multi-epitope long peptide, TAS0314, which induced multiple epitope-specific CTLs in HLA knock-in mice. It also showed superior epitope-specific CTL induction and antitumor activity. We also established a combination treatment model of vaccination with PD-1/PD-L1 blockade in HLA-A*2402 knock-in mice, and it showed a synergistic antitumor effect with TAS0314. Thus, our data indicated that TAS0314 treatment, especially in combination with PD-1/PD-L1 blockade, is a promising therapeutic candidate for cancer immunotherapy.
Systematic evaluation of particle loss during handling in the percutaneous transluminal angioplasty for eight different drug-coated balloons
Authors: Heinrich Andreas , Engler Martin S. , Güttler Felix V. , Matthäus Christian , Popp Jürgen , Teichgräber Ulf K.-M. 
Published: October 2020

AbstractPaclitaxel drug coated balloons (DCBs) should provide optimal drug transfer exclusively to the target tissue. The aim of this study was to evaluate the particle loss by handling during angioplasty. A robotic arm was developed for systematic and reproducible drug abrasion experiments. The contact force on eight different commercially available DCB types was gradually increased, and high-resolution microscopic images of the deflated and inflated balloons were recorded. Three types of DCBs were classified: no abrasion of the drug in both statuses (deflated and inflated), significant abrasion only in the inflated status, and significant abrasion in both statuses. Quantitative measurements via image processing confirmed the qualitative classification and showed changes of the drug area between 2.25 and 45.73% (13.28 ± 14.29%) in the deflated status, and between 1.66 and 40.41% (21.43 ± 16.48%) in the inflated status. The structures and compositions of the DCBs are different, some are significantly more susceptible to drug loss. Particle loss by handling during angioplasty leads to different paclitaxel doses in the target regions for same DCB types. Susceptibility to involuntary drug loss may cause side effects, such as varying effective paclitaxel doses, which may explain variations in studies regarding the therapeutic outcome.
A practical method for multimodal registration and assessment of whole-brain disease burden using PET, MRI, and optical imaging
Authors: Scarpelli Matthew L. , Healey Debbie R. , Mehta Shwetal , Kodibagkar Vikram D. , Quarles Christopher C. 
Published: October 2020

AbstractMany neurological diseases present with substantial genetic and phenotypic heterogeneity, making assessment of these diseases challenging. This has led to ineffective treatments, significant morbidity, and high mortality rates for patients with neurological diseases, including brain cancers and neurodegenerative disorders. Improved understanding of this heterogeneity is necessary if more effective treatments are to be developed. We describe a new method to measure phenotypic heterogeneity across the whole rodent brain at multiple spatial scales. The method involves co-registration and localized comparison of in vivo radiologic images (e.g. MRI, PET) with ex vivo optical reporter images (e.g. labeled cells, molecular targets, microvasculature) of optically cleared tissue slices. Ex vivo fluorescent images of optically cleared pathology slices are acquired with a preclinical in vivo optical imaging system across the entire rodent brain in under five minutes, making this methodology practical and feasible for most preclinical imaging labs. The methodology is applied in various examples demonstrating how it might be used to cross-validate and compare in vivo radiologic imaging with ex vivo optical imaging techniques for assessing hypoxia, microvasculature, and tumor growth.
Observation of crystallisation dynamics by crystal-structure-sensitive room-temperature phosphorescence from Au(I) complexes
Authors: Kuroda Yuki , Tamaru Masakazu , Nakasato Hitoya , Nakamura Kyosuke , Nakata Manami , Hisano Kyohei , Fujisawa Kaori , Tsutsumi Osamu 
Published: October 2020

AbstractThe aggregation behaviour of Au(I) complexes in condensed phases can affect their emission properties. Herein, aggregation-induced room-temperature phosphorescence (RTP) is observed from the crystals of trinuclear Au(I) complexes. The RTP is highly sensitive to the crystal structure, with a slight difference in the alkyl side chains causing not only a change in the crystal structure but also a shift in the RTP maximum. Furthermore, in nanocrystals, reversible RTP colour changes are induced by phase transitions between crystal polymorphs during crystal growth from solution or the pulverisation of bulk crystals. The colour change mechanism is discussed in terms of intermolecular interactions in the crystal structure of the luminescent aggregates. The results suggest that the behaviour in nanocrystals may differ from that in bulk crystals. These insights will advance the fundamental understanding of crystallisation mechanisms and may aid in the discovery of new materials properties for solids with nano- to micrometre sizes.
Historically-based run-time bias corrections substantially improve model projections of 100 years of future climate change
Authors: Krinner Gerhard , Kharin Viatcheslav , Roehrig Romain , Scinocca John , Codron Francis 
Published: October 2020

AbstractClimate models and/or their output are usually bias-corrected for climate impact studies. The underlying assumption of these corrections is that climate biases are essentially stationary between historical and future climate states. Under very strong climate change, the validity of this assumption is uncertain, so the practical benefit of bias corrections remains an open question. Here, this issue is addressed in the context of bias correcting the climate models themselves. Employing the ARPEGE, LMDZ and CanAM4 atmospheric models, we undertook experiments in which one centre’s atmospheric model takes another centre’s coupled model as observations during the historical period, to define the bias correction, and as the reference under future projections of strong climate change, to evaluate its impact. This allows testing of the stationarity assumption directly from the historical through future periods for three different models. These experiments provide evidence for the validity of the new bias-corrected model approach. In particular, temperature, wind and pressure biases are reduced by 40–60% and, with few exceptions, more than 50% of the improvement obtained over the historical period is on average preserved after 100 years of strong climate change. Below 3 °C global average surface temperature increase, these corrections globally retain 80% of their benefit.
A parametric two-mode vibronic model of a dimeric mixed-valence cell for molecular quantum cellular automata and computationalab initioverification
Authors: Palii Andrew , Aldoshin Sergey , Zilberg Shmuel , Tsukerblat Boris 
Published: October 2020

Here we propose a two-mode vibronic model of a molecular cell for quantum cellular automata. The interconnection between the parametric approach and ab initio evaluations for the cation-radical of tetramethyleneethane molecule is established.
In silico and in vitro analysis of FAK/MMP signaling axis inhibition by VO-clioquinol in 2D and 3D human osteosarcoma cancer cells
Authors: Balsa Lucia M , Quispe Patricia , Baran Enrique J , Lavecchia Martin J , León Ignacio E 
Published: October 2020

Abstract
The study of novel mechanisms of action of vanadium compounds is critical to elucidating the role and importance of these kinds of compounds as antitumor and antimetastatic agents. This work deals with in silico and in vitro studies of one clioquinol oxidovanadium(iv) complex [VO(clioquinol)2], VO(CQ)2, and its regulation of FAK. In particular, we focus on elucidating the relationship of the FAK inhibition, MMP activity and antimetastatic effects of the complex in human bone cancer cells.
Blood Pressure Response to Muscle Metaboreflex Activation is Impaired in Men Living with HIV
Authors: Gama Gabriel , Farinatti Paulo , Crisafulli Antonio , Borges Juliana 
Published: October 2020

AbstractWe investigated the muscle metaboreflex contribution to blood pressure response during dynamic handgrip exercise in men living with HIV (MLHIV) vs. without HIV (Controls). Pressor and heart rate responses were evaluated during metaboreflex activation through post-exercise muscle ischemia (PEMI) method and control exercise session (CER) in 17 MLHIV and 21 Controls. Protocols were performed randomly on the same day, being both sessions composed of 12 min, as follows: a) 3 min at rest, b) 3 min of dynamic handgrip exercise at 30% of maximal voluntary contraction, c) 3 min of recovery post-exercise with vascular occlusion (occlusion only in PEMI), and d) 3 min of recovery post-exercise without vascular occlusion. To assess metaboreflex response, differences between PEMI and CER in recovery post-exercise were calculated for blood pressure and heart rate. Systolic and mean blood pressure (P<0.01) were superior in the last 2 min of recovery with vascular occlusion at PEMI in relation to CER for both groups. No difference was found between groups for blood pressure and heart rate (P>0.05). However, metaboreflex response for systolic blood pressure was lower in MLHIV vs. Controls (4.05±4.63 vs. 7.61±3.99 mmHg; P=0.01). In conclusion, pressor response during metaboreceptor stimulation was attenuated in men living with HIV, which may suggest loss of muscle metaboreflex sensibility.
Convergent Synthesis of Immune Inhibitor IMMH002
Authors: Xiao Qiong , Chen Si , Shi Zeyu , Yin Dali 
Published: October 2020

AbstractA convergent synthesis of IMMH002 in 36% overall yield starting from bromobenzene is described with a key Suzuki–Miyaura cross-coupling reaction used to provide a crucial intermediate. The route does not require column chromatography and solves the most intractable quality problem caused by a homologue by-product in the original linear synthesis. Furthermore, reducing the use of Lewis acid mediated reactions improves the environmental impact of the synthesis and reduces overall waste. The new route described herein is more efficient, convenient, reliable, and economically more viable when compared to the previously reported linear route.