bluuebunny/crossref_metadata_2025_split huggingface dataset:
Estrogen receptor coregulator binding modulator (ERX-11) enhances the activity of CDK4/6 inhibitors against estrogen receptor-positive breast cancers
Authors: Viswanadhapalli Suryavathi , Ma Shihong , Sareddy Gangadhara Reddy , Lee Tae-Kyung , Li Mengxing , Gilbreath Collin , Liu Xihui , Luo Yiliao , Pratap Uday P. , Zhou Mei , Blatt Eliot B. , Kassees Kara , Arteaga Carlos , Alluri Prasanna , Rao Manjeet , Weintraub Susan T. , Tekmal Rajeshwar Rao , Ahn Jung-Mo , Raj Ganesh V. , Vadlamudi Ratna K. 
Published: December 2019

Abstract
Background
CDK4/6 inhibitors in combination with endocrine therapy (AE/AI/SERDs) are approved for the treatment of ER+ advanced breast cancer (BCa). However, not all patients benefit from CDK4/6 inhibitors therapy. We previously reported a novel therapeutic agent, ERX-11, that binds to the estrogen receptor (ER) and modulates ER-coregulator interactions. Here, we tested if the combination of ERX-11 with agents approved for ER+ BCa would be more potent.

Methods
We tested the effect of combination therapy using BCa cell line models, including those that have acquired resistance to tamoxifen, letrozole, or CDK4/6 inhibitors or have been engineered to express mutant forms of the ER. In vitro activity was tested using Cell Titer-Glo, MTT, and apoptosis assays. Mechanistic studies were conducted using western blot, reporter gene assays, RT-qPCR, and mass spectrometry approaches. Xenograft, patient-derived explants (PDEs), and xenograft-derived explants (XDE) were used for preclinical evaluation and toxicity.

Results
ERX-11 inhibited the proliferation of therapy-resistant BCa cells in a dose-dependent manner, including ribociclib resistance. The combination of ERX-11 and CDK4/6 inhibitor was synergistic in decreasing the proliferation of both endocrine therapy-sensitive and endocrine therapy-resistant BCa cells, in vitro, in xenograft models in vivo, xenograft-derived explants ex vivo, and in primary patient-derived explants ex vivo. Importantly, the combination caused xenograft tumor regression in vivo. Unbiased global mass spectrometry studies demonstrated profound decreases in proliferation markers with combination therapy and indicated global proteomic changes in E2F1, ER, and ER coregulators. Mechanistically, the combination of ERX-11 and CDK4/6 inhibitor decreased the interaction between ER and its coregulators, as evidenced by immunoprecipitation followed by mass spectrometry studies. Biochemical studies confirmed that the combination therapy significantly altered the expression of proteins involved in E2F1 and ER signaling, and this is primarily driven by a transcriptional shift, as noted in gene expression studies.

Conclusions
Our results suggest that ERX-11 inhibited the proliferation of BCa cells resistant to both endocrine therapy and CDK4/6 inhibitors in a dose-dependent manner and that the combination of ERX-11 with a CDK4/6 inhibitor may represent a viable therapeutic approach.
Comprehensive evaluation of methods to assess overall and cell-specific immune infiltrates in breast cancer
Authors: Nederlof Iris , De Bortoli Davide , Bareche Yacine , Nguyen Bastien , de Maaker Michiel , Hooijer Gerrit K. J. , Buisseret Laurence , Kok Marleen , Smid Marcel , Van den Eynden Gert G. G. M. , Brinkman Arie B. , Hudecek Jan , Koster Jan , Sotiriou Christos , Larsimont Denis , Martens John W. M. , van de Vijver Marc J. , Horlings Hugo M. , Salgado Roberto , Biganzoli Elia , Desmedt Christine 
Published: December 2019

Abstract
Background
Breast cancer (BC) immune infiltrates play a critical role in tumor progression and response to treatment. Besides stromal tumor infiltrating lymphocytes (sTILs) which have recently reached level 1B evidence as a prognostic marker in triple negative BC, a plethora of methods to assess immune infiltration exists, and it is unclear how these compare to each other and if they can be used interchangeably.

Methods
Two experienced pathologists scored sTIL, intra-tumoral TIL (itTIL), and 6 immune cell types (CD3+, CD4+, CD8+, CD20+, CD68+, FOXP3+) in the International Cancer Genomics Consortium breast cancer cohort using hematoxylin and eosin-stained (n = 243) and immunohistochemistry-stained tissue microarrays (n = 254) and whole slides (n = 82). The same traits were evaluated using transcriptomic- and methylomic-based deconvolution methods or signatures.

Results
The concordance correlation coefficient (CCC) between pathologists for sTIL was very good (0.84) and for cell-specific immune infiltrates slightly lower (0.63–0.66). Comparison between tissue microarray and whole slide pathology scores revealed systematically higher values in whole slides (ratio 2.60–5.98). The Spearman correlations between microscopic sTIL and transcriptomic- or methylomic-based assessment of immune infiltrates were highly variable (r = 0.01–0.56). Similar observations were made for cell type-specific quantifications (r = 0.001–0.54). We observed a strong inter-method variability between the omics-derived estimations, which is further cell type dependent. Finally, we demonstrated that most methods more accurately identify highly infiltrated (sTIL ≥ 60%; area under the curve, AUC, 0.64–0.99) as compared to lowly infiltrated tumors (sTIL ≤ 10%; AUC 0.52–0.82).

Conclusions
There is a lower inter-pathologist concordance for cell-specific quantification as compared to overall infiltration quantification. Microscopic assessments are underestimated when considering small cores (tissue microarray) instead of whole slides. Results further highlight considerable differences between the microscopic-, transcriptomic-, and methylomic-based methods in the assessment of overall and cell-specific immune infiltration in BC. We therefore call for extreme caution when assessing immune infiltrates using current methods and emphasize the need for standardized immune characterization beyond TIL.
Establishment of an innovative and sustainable PCR technique for 1534 locus mutation of the knockdown resistance (kdr) gene in the dengue vector Aedes albopictus
Authors: Zhu Cai-Ying , Zhao Chun-Chun , Wang Yi-Guan , Ma De-Ling , Song Xiu-Ping , Wang Jun , Meng Feng-Xia 
Published: December 2019

AbstractBackgroundMutation of the voltage-gated sodium channel (VGSC) gene, or knockdown resistance (kdr) gene, is an important resistance mechanism against DDT and pyrethroids for dengue vectorAedes albopictus. A phenylalanine to serine (F1534S), leucine (F1534L) and cysteine (F1534C) substitution were detected in manyAe. albopictuspopulations around the world, and the mutant allele frequencies have been increasing in recent years. Therefore, it is essential to establish a simple, time-saving and cost-effective procedure to monitor the alleles in large-scale studies.MethodsBased on the mutation genotypes of the 1534 locus in thekdrgene, F/F, F/S, F/C, F/L, S/S, C/C, L/L and S/C, we designed specific forward and reverse primers and optimized the reaction conditions for establishing of the allele-specific PCR(AS-PCR) detection technique. DNA sequencing in this study was taken as the gold standard, and used to determine the accuracy of AS-PCR.ResultsThe designed AS-PCR technique showed high specificity for distinguishing the mutations at the 1534 locus, as the accuracy for F/F, F/S, F/C, F/L, S/S, C/C and S/C were 100%, 95.35%, 100%, 100%, 100%, 100% and 100%, respectively.ConclusionsThe designed AS-PCR technique effectively distinguished individual genotypes for the mutations at the 1534 locus in thekdrgene, which could facilitate the knockdown resistance surveillance inAe. albopictusin large-scale studies.
Draft genome of Ompok bimaculatus (Pabda fish)
Authors: Dhar Ruby , Pethusamy Karthikeyan , Singh Sunil , Mukherjee Indrani , Seethy Ashikh , Sengupta Bharoti , Srivastava Tryambak , Sarkar Sajib , Mandal Vikramjit , Karmakar Madhumita , Gupta Sandipan , Ghosh Arpita , Karmakar Subhradip 
Published: December 2019

Abstract
Objective
Pabda (Ompok bimaculatus) is a freshwater catfish, largely available in Asian countries, especially in Bangladesh, India, Pakistan and Nepal. This fish is highly valued for its fabulous taste and high nutritional value and is very popular as a rich source of proteins, omega-3 and omega-6 fatty acids, vitamins and mineral for growing children, pregnant females and elders. We performed de-novo sequencing of Ompok bimaculatus using a hybrid approach and present here a draft assembly for this species for the first time.

Data Description
The genome of Ompok bimaculatus (Fig. 1: Table 1, Data file 3) from Ganges river, has been sequenced by hybrid approach using Illumina short reads and PacBio long reads followed by structural annotations. The draft genome assembly was found to be 718 Mb with N50 size of 81 kb. MAKER gene annotation tool predicted 21,371 genes.
Psychotropic drug-induced genetic-epigenetic modulation of CRTC1 gene is associated with early weight gain in a prospective study of psychiatric patients
Authors: Delacrétaz Aurélie , Glatard Anaïs , Dubath Céline , Gholam-Rezaee Mehdi , Sanchez-Mut Jose Vicente , Gräff Johannes , von Gunten Armin , Conus Philippe , Eap Chin B. 
Published: December 2019

Abstract
Background
Metabolic side effects induced by psychotropic drugs represent a major health issue in psychiatry. CREB-regulated transcription coactivator 1 (CRTC1) gene plays a major role in the regulation of energy homeostasis and epigenetic mechanisms may explain its association with obesity features previously described in psychiatric patients. This prospective study included 78 patients receiving psychotropic drugs that induce metabolic disturbances, with weight and other metabolic parameters monitored regularly. Methylation levels in 76 CRTC1 probes were assessed before and after 1 month of psychotropic treatment in blood samples.

Results
Significant methylation changes were observed in three CRTC1 CpG sites (i.e., cg07015183, cg12034943, and cg 17006757) in patients with early and important weight gain (i.e., equal or higher than 5% after 1 month; FDR p value = 0.02). Multivariable models showed that methylation decrease in cg12034943 was more important in patients with early weight gain (≥ 5%) than in those who did not gain weight (p = 0.01). Further analyses combining genetic and methylation data showed that cg12034943 was significantly associated with early weight gain in patients carrying the G allele of rs4808844A>G (p = 0.03), a SNP associated with this methylation site (p = 0.03).

Conclusions
These findings give new insights on psychotropic-induced weight gain and underline the need of future larger prospective epigenetic studies to better understand the complex pathways involved in psychotropic-induced metabolic side effects.
Positive bound state solutions for the nonlinear Schrödinger–Poisson systems with potentials
Authors: Yang Jing 
Published: December 2019

AbstractIn this paper, we study the following Schrödinger–Poisson system in $\mathbb{R} ^{3}$R3$$ \textstyle\begin{cases} (-\Delta )^{\sigma }u+A(y)u+B(y)\phi (y)u=b(y) \vert u \vert ^{p-1}u, & y \in \mathbb{R} ^{3}, \\ (-\Delta )^{\sigma }\phi =B(y)u^{2}, & y\in \mathbb{R} ^{3}, \end{cases} $${(−Δ)σu+A(y)u+B(y)ϕ(y)u=b(y)|u|p−1u,y∈R3,(−Δ)σϕ=B(y)u2,y∈R3, with $\frac{3}{4}<\sigma <1$34<σ<1, $p\in (3,\frac{3+2\sigma }{3-2 \sigma })$p∈(3,3+2σ3−2σ). Then, under some suitable assumptions on the coefficients not requiring any symmetry property, we prove the existence of a bound state solution of the above problem.
Egg rejection behavior does not explain the lack of cowbird parasitism on an eastern North American population of Red-winged Blackbirds
Authors: Reel Justin J. , Underwood Todd J. 
Published: December 2019

AbstractBackgroundRed-winged Blackbirds (Agelaius phoeniceus), hereafter red-wings, are much less frequently parasitized by Brown-headed Cowbirds (Molothrus ater) in eastern North America than in central North America and had not been recorded as hosts in our study area in southeastern Pennsylvania. Although hosts of Old World cuckoos (Cuculidae) often show geographic variation in egg rejection behavior, cowbird hosts typically exhibit uniform responses of all acceptance or all rejection of cowbird eggs. Thus, geographic variation in cowbird parasitism frequencies might reflect a different behavioral response to parasitism by hosts where only some populations reject parasitism. In this study, we tested whether egg rejection behavior may explain the lack of parasitism observed in our eastern red-wing population, which may provide insight into low parasitism levels across eastern North America.MethodsWe parasitized red-wing nests with model cowbird eggs to determine their response to parasitism. Nests were tested across three nest stages and compared to control nests with no manipulations. Because rejection differed significantly by stage, we compared responses separately for each nest stage. We also monitored other songbird nests to identify parasitism frequencies on all potential hosts.ResultsRed-wings showed significantly more rejections during the building stage, but not for the laying and incubation stages. Rejections during nest building involved mostly egg burials, which likely represent a continuation of the nest building process rather than true rejection of the cowbird egg. Excluding these responses, red-wings rejected 15% of cowbird eggs, which is similar to rejection levels from other studies and populations. The overall parasitism frequency on 11 species surveyed in our study area was only 7.4%.ConclusionsEgg rejection behavior does not explain the lack of parasitism on red-wings in our eastern population. Alternatively, we suggest that cowbird preference for other hosts and the low abundance of cowbirds in the east might explain the lack of parasitism. Future research should also explore cowbird and host density and the makeup of the host community to explain the low levels of parasitism on red-wings across eastern North America because egg rejection alone is unlikely to explain this broad geographic trend.
Quantitative implications of the updated EARL 2019 PET–CT performance standards
Authors: Kaalep Andres , Burggraaff Coreline N. , Pieplenbosch Simone , Verwer Eline E. , Sera Terez , Zijlstra Josee , Hoekstra Otto S. , Oprea-Lager Daniela E. , Boellaard Ronald 
Published: December 2019

Abstract
Purpose
Recently, updated EARL specifications (EARL2) have been developed and announced. This study aims at investigating the impact of the EARL2 specifications on the quantitative reads of clinical PET–CT studies and testing a method to enable the use of the EARL2 standards whilst still generating quantitative reads compliant with current EARL standards (EARL1).

Methods
Thirteen non-small cell lung cancer (NSCLC) and seventeen lymphoma PET–CT studies were used to derive four image datasets—the first dataset complying with EARL1 specifications and the second reconstructed using parameters as described in EARL2. For the third (EARL2F6) and fourth (EARL2F7) dataset in EARL2, respectively, 6 mm and 7 mm Gaussian post-filtering was applied. We compared the results of quantitative metrics (MATV, SUVmax, SUVpeak, SUVmean, TLG, and tumor-to-liver and tumor-to-blood pool ratios) obtained with these 4 datasets in 55 suspected malignant lesions using three commonly used segmentation/volume of interest (VOI) methods (MAX41, A50P, SUV4).

Results
We found that with EARL2 MAX41 VOI method, MATV decreases by 22%, TLG remains unchanged and SUV values increase by 23–30% depending on the specific metric used. The EARL2F7 dataset produced quantitative metrics best aligning with EARL1, with no significant differences between most of the datasets (p>0.05). Different VOI methods performed similarly with regard to SUV metrics but differences in MATV as well as TLG were observed. No significant difference between NSCLC and lymphoma cancer types was observed.

Conclusions
Application of EARL2 standards can result in higher SUVs, reduced MATV and slightly changed TLG values relative to EARL1. Applying a Gaussian filter to PET images reconstructed using EARL2 parameters successfully yielded EARL1 compliant data.
Towards standardization of absolute SPECT/CT quantification: a multi-center and multi-vendor phantom study
Authors: Peters Steffie M. B. , van der Werf Niels R. , Segbers Marcel , van Velden Floris H. P. , Wierts Roel , Blokland Koos A. K. , Konijnenberg Mark W. , Lazarenko Sergiy V. , Visser Eric P. , Gotthardt Martin 
Published: December 2019

Abstract
Absolute quantification of radiotracer distribution using SPECT/CT imaging is of great importance for dosimetry aimed at personalized radionuclide precision treatment. However, its accuracy depends on many factors. Using phantom measurements, this multi-vendor and multi-center study evaluates the quantitative accuracy and inter-system variability of various SPECT/CT systems as well as the effect of patient size, processing software and reconstruction algorithms on recovery coefficients (RC).

Methods
Five SPECT/CT systems were included: Discovery™ NM/CT 670 Pro (GE Healthcare), Precedence™ 6 (Philips Healthcare), Symbia Intevo™, and Symbia™ T16 (twice) (Siemens Healthineers). Three phantoms were used based on the NEMA IEC body phantom without lung insert simulating body mass indexes (BMI) of 25, 28, and 47 kg/m2. Six spheres (0.5–26.5 mL) and background were filled with 0.1 and 0.01 MBq/mL 99mTc-pertechnetate, respectively. Volumes of interest (VOI) of spheres were obtained by a region growing technique using a 50% threshold of the maximum voxel value corrected for background activity. RC, defined as imaged activity concentration divided by actual activity concentration, were determined for maximum (RCmax) and mean voxel value (RCmean) in the VOI for each sphere diameter. Inter-system variability was expressed as median absolute deviation (MAD) of RC. Acquisition settings were standardized. Images were reconstructed using vendor-specific 3D iterative reconstruction algorithms with institute-specific settings used in clinical practice and processed using a standardized, in-house developed processing tool based on the SimpleITK framework. Additionally, all data were reconstructed with a vendor-neutral reconstruction algorithm (Hybrid Recon™; Hermes Medical Solutions).

Results
RC decreased with decreasing sphere diameter for each system. Inter-system variability (MAD) was 16 and 17% for RCmean and RCmax, respectively. Standardized reconstruction decreased this variability to 4 and 5%. High BMI hampers quantification of small lesions (< 10 ml).

Conclusion
Absolute SPECT quantification in a multi-center and multi-vendor setting is feasible, especially when reconstruction protocols are standardized, paving the way for a standard for absolute quantitative SPECT.
A case of subcutaneous emphysema/mediastinal emphysema during the use of humidified high-flow nasal cannula
Authors: Sonobe Shota , Inoue Satoki , Nishiwada Tadashi , Egawa Junji , Kawaguchi Masahiko 
Published: December 2019

Abstract
Background
Heated, humidified, high-flow nasal cannula (HHFNC) oxygen therapy allows optimal humidification of inspired gas at high flows and creates a distending pressure similar to nasal continuous positive airway pressure [1]. It has been safely used in adults with moderate hypoxemia with few complications [2, 3]. Hereby, we report serious complications occurred during HHFNC oxygen therapy.

Case presentation
A 53-year-old female with hemophagocytic lymphohistiocytosis (HLH) was admitted to the intensive care unit because of respiratory failure. After weaning from mechanical ventilation which lasted for 2 weeks, HHFNC therapy at 40 L/min with an FiO2 of 0.5 was started for hypoxemia. Four days later, dyspnea and hypoxemia occurred and chest X-ray and CT scan revealed localized pneumothorax, subcutaneous emphysema, and massive pneumomediastinum. After cessation of HHFNC, respiratory condition improved.

Conclusion
Subcutaneous emphysema, pneumothorax, and pneumomediastinum should be notified as a serious complication during HHFNC therapy.
Response of two seed-grown artichoke cultivars to GA3 and melatonin treatments
Authors: Ezzo M. I. , Saleh Said A. , Abd El-Naby Saied K. M. , Khalifa Ramadan K. M. 
Published: December 2019

AbstractBackgroundGlobe artichokeCynara scolymusL. is an important vegetable crop. Poor crop stand due to the low ratio of stumps surviving is the common problem which occurs with using vegetative parts. The current study evaluated two seed-propagated cultivars of artichoke: treated by GA3and melatonin applications in newly reclaimed land.ResultsResults showed that Imperial Star produced higher values of vegetative growth, yield productivity, and chemical contents, compared with Romanesco cultivar. GA3foliar application treatment ranked the first to increase vegetative growth, yield productivity, and chemical contents, followed by melatonin treatment, compared with untreated control.ConclusionIt could be concluded that the use of GA3and melatonin were favorable for the production of both artichoke cultivars: Imperial Star and Romanesco. The highest productivity was achieved by foliar application of GA3to Imperial Star cultivar.
Outcome of Men With Relapses After Adjuvant Bleomycin, Etoposide, and Cisplatin for Clinical Stage I Nonseminoma
Authors: Fischer Stefanie , Tandstad Torgrim , Cohn-Cedermark Gabriella , Thibault Constance , Vincenzi Bruno , Klingbiel Dirk , Albany Costantine , Necchi Andrea , Terbuch Angelika , Lorch Anja , Aparicio Jorge , Heidenreich Axel , Hentrich Marcus , Wheater Matthew , Langberg Carl W. , Ståhl Olof , Fankhauser Christian Daniel , Hamid Anis A. , Koutsoukos Konstantinos , Shamash Jonathan , White Jeff , Bokemeyer Carsten , Beyer Jörg , Gillessen Silke ,   on behalf of the Global Germ-Cell Cancer Group
Published: December 2019

PURPOSE Clinical stage I (CSI) nonseminoma (NS) is a disease limited to the testis without metastases. One treatment strategy after orchiectomy is adjuvant chemotherapy. Little is known about the outcome of patients who experience relapse after such treatment. PATIENTS AND METHODS Data from 51 patients with CSI NS who experienced a relapse after adjuvant bleomycin, etoposide, and cisplatin (BEP) from 18 centers/11 countries were collected and retrospectively analyzed. Primary outcomes were overall and progression-free survivals calculated from day 1 of treatment at first relapse. Secondary outcomes were time to, stage at, and treatment of relapse and rate of subsequent relapses. RESULTS Median time to relapse was 13 months, with the earliest relapse 2 months after start of adjuvant treatment and the latest after 25 years. With a median follow-up of 96 months, the 5-year PFS was 67% (95% CI, 54% to 82%) and the 5-year OS was 81% (95% CI, 70% to 94%). Overall, 19 (37%) of 51 relapses occurred later than 2 years. Late relapses were associated with a significantly higher risk of death from NS (hazard ratio, 1.10 per year; P = .01). Treatment upon relapse was diverse: the majority of patients received a combination of chemotherapy and surgery. Twenty-nine percent of patients experienced a subsequent relapse. At last follow-up, 41 patients (80%) were alive and disease-free, eight (16%) had died of progressive disease, and one patient (2%) each had died from therapy-related or other causes. CONCLUSION Outcomes of patients with relapse after adjuvant BEP seem better compared with patients who experience relapse after treatment of metastatic disease but worse compared with those who have de-novo metastatic disease. We found a substantial rate of late and subsequent relapses. There seem to be three patterns of relapse with different outcomes: pure teratoma, early viable NS relapse (< 2 years), and late viable NS relapse (> 2 years).