bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase I/II Study of the Mesothelin-targeted Immunotoxin LMB-100 with Nab-Paclitaxel for Patients with Advanced Pancreatic Adenocarcinoma
Authors: Alewine Christine , Ahmad Mehwish , Peer Cody J. , Hu Zishuo I. , Lee Min-Jung , Yuno Akira , Kindrick Jessica D. , Thomas Anish , Steinberg Seth M. , Trepel Jane B. , Figg William D. , Hassan Raffit , Pastan Ira 
Published: December 2019

Abstract

Purpose:
LMB-100 is a recombinant immunotoxin (iTox) consisting of a mesothelin-binding Fab for targeting and a modified Pseudomonas exotoxin A payload. Preclinical studies showed that combining taxanes with iTox results in synergistic antitumor activity. The objectives of this phase I/II study were to determine the MTD of LMB-100 when administered with nanoalbumin bound (nab)-paclitaxel to patients with previously treated advanced pancreatic adenocarcinoma and to assess the objective response rate.

Patients and Methods:
Patients (n = 20) received fixed-dose nab-paclitaxel (125 mg/m2 on days 1 and 8) with LMB-100 (65 or 100 μg/kg on days 1, 3, and 5) in 21-day cycles for 1–3 cycles.

Results:
Fourteen patients were treated on the dose escalation and an additional six in the phase II expansion. MTD of 65 μg/kg was established for the combination. Dose-limiting toxicity resulting from capillary leak syndrome (CLS) was seen in two of five patients treated at 100 μg/kg and one of six evaluable phase I patients receiving the MTD. Severity of CLS was associated with increases in apoptotic circulating endothelial cells. LMB-100 exposure was unaffected by anti-LMB-100 antibody formation in five of 13 patients during cycle 2. Seven of 17 evaluable patients experienced &gt;50% decrease in CA 19-9, including three with previous exposure to nab-paclitaxel. One patient developed an objective partial response. Patients with biomarker responses had higher tumor mesothelin expression.

Conclusions:
Although clinical activity was observed, the combination was not well tolerated and alternative drug combinations with LMB-100 will be pursued.
Cabozantinib in Combination with Immunotherapy for Advanced Renal Cell Carcinoma and Urothelial Carcinoma: Rationale and Clinical Evidence
Authors: Bergerot Paulo , Lamb Peter , Wang Evelyn , Pal Sumanta K. 
Published: December 2019

Abstract
The treatment landscape for metastatic renal cell carcinoma (mRCC) and urothelial carcinoma (mUC) has evolved rapidly in recent years with the approval of several checkpoint inhibitors. Despite these advances, survival rates for metastatic disease remain poor, and additional strategies will be needed to improve the efficacy of checkpoint inhibitors. Combining anti-VEGF/VEGFR agents with checkpoint inhibitors has emerged as a potential strategy to advance the immunotherapy paradigm, because VEGF inhibitors have immunomodulatory potential. Cabozantinib is a tyrosine kinase inhibitor (TKI) whose targets include MET, AXL, and VEGFR2. Cabozantinib has a unique immunomodulatory profile and has demonstrated clinical efficacy as a monotherapy in mRCC and mUC, making it a potentially suitable partner for checkpoint inhibitor therapy. In this review, we summarize the current status of immunotherapy for mRCC and mUC and discuss the development of immunotherapy–TKI combinations, with a focus on cabozantinib. We discuss the rationale for such combinations based on our growing understanding of the tumor microenvironment, and we review in detail the preclinical and clinical studies supporting their use.
Oncogenic Drivers and Development
Authors: Cruz Hernandez David , Vyas Paresh 
Published: December 2019

Abstract

Summary:
In this issue of Cancer Discovery, Lopez and colleagues show that the aggressive acute leukemic phenotype caused by the chimeric transcription factor CBFA2T3–GLIS2 varies depending on the developmental stage of the cell transformed (i.e., fetal vs. adult). This is likely a general principle in pediatric cancers and begins to explain why some cancer phenotypes are more common in infants and young children, whereas others are more frequent in older individuals.
See related article by Lopez et al., p. 1736.
ВІЛ-ІНФЕКЦІЯ І СТАРІННЯ: НОВА ПРОБЛЕМА В ЕРУ ЕФЕКТИВНОЇ АНТИРЕТРОВІРУСНОЇ ТЕРАПІЇ
Authors: Zhyvytsia D. H. 
Published: December 2019

Після запровадження ефективної антиретровірусної терапії у світі значно зросла частка літніх пацієнтів з ВІЛ-інфекцією. Сьогодні 27 % ВІЛ-інфікованих пацієнтів у Західній Європі та США віком від 50 років. В Україні кількість та відсоток цих пацієнтів також поступово збільшуються. Постійне застосування антиретровірусної терапії сприяло різкому зменшенню захворюваності на опортуністичні інфекції та дозволило пацієнтам з ВІЛ жити довше. Стійка активація імунітету та хронічне запалення, яке зазвичай характеризує імунологічне старіння, є важливим фактором для розвитку супутніх захворювань у пацієнтів з ВІЛ-інфекцією. Біологічні процеси, які співвідносяться зі старінням, відбуваються раніше у дорослих ВІЛ-інфікованих пацієнтів. Важливі супутні захворювання, що з’являються з віком (метаболічний синдром, нейро­когнітивні розлади, серцево-судинні захворювання, остеопороз, синдром старечої астенії і онкологічні захворювання), є більш поширеними у ВІЛ-інфікованих, ніж у ВІЛ-неінфікованих осіб. У цьому огляді буде розглянуто роль імунної активації і хронічного запалення в розвитку найважливіших, асоційованих зі старінням захворювань у ВІЛ-інфікованих пацієнтів.
ВПРОВАДЖЕННЯ МЕДИЧНОЇ ГЕОІНФОРМАЦІЙНОЇ СИСТЕМИ ПРИ ДОСЛІДЖЕННЯХ ІКСОДОВИХ КЛІЩІВ І КЛІЩОВИХ ІНФЕКЦІЙ В УКРАЇНІ
Authors: Podobivsky S. S. , Fedoniuk L. Ya. , Korda M. M. , Klishch I. M. , Andreychyn M. A. , Shkilna M. I. , Podobivsky V. S. , Nykytiuk S. O. 
Published: December 2019

Мета роботи – створити медичну геоінформаційну систему на базі отриманих даних про кліщів, зібраних з тіла людей і домашніх тварин в межах м. Тернополя, Тернопільської та інших областей України, де проводилися польові дослідження; узагальнити та систематизувати дані про клінічний стан пацієнтів, уражених іксодовими кліщами за період польових і лабораторних досліджень.
Матеріали і методи. Ідентифікацію іксодових кліщів здійснювали за допомогою оптико-електронної системи SEO – IMAGLAB. Визначення збудників, яких переносили добуті кліщі, проводилось за допомогою методу полімеразно-ланцюгової реакції (ПЛР) шляхом приготування суспензії кліщів, виділення самої ДНК та проведення подальшої ампліфікації з використанням ампліфікатора «ROTORGene–6000» в «реальному часі».
За основу створеної медичної геоінформаційної системи (ГІС) була взята платформа ArcGIS.
Результати. Створена ГІС дає можливість он-лайн бачити поширення кліщів, зумовлених ними інфекцій та пацієнтів, у яких ці інфекції виявлені, в м. Тернополі, Тернопільській, Житомирській, Хмельницькій, Закарпатській та інших областях України. Операційні можливості ГІС дозволяють узагальнювати результати у вигляді таблиць, графіків і діаграм, здійснювати пошуки кліщів і пацієнтів за ідентифікаційним номером і т. п.
Висновки. Застосування медичної ГІС під час дослідження морфо-фізіологічних, біологічних та епідеміологічних особливостей іксодових кліщів дає можливість отримувати просторові уявлення та демонструвати отримані результати, важливе у плані узагальнення та впорядкування даних про стан пацієнтів, атакованих кліщами і заражених різними видами збудників інфекційних захворювань на певних територіях. Медична ГІС може використовуватися у прогнозуванні епідеміологічної небезпеки у населених пунктах і окремих регіонах.
<p><strong>Capitalised epithets in the works of Linnaeus (1758‒1767): findings and consequences in herpetology</strong></p>
Authors: FRÉTEY THIERRY 
Published: December 2019

Starting from a finding concerning a few specific nomina proposed by Linnaeus (1758, 1760) and Linné (1766–1767) in herpetology, we returned to the ‘rules of nomenclature’ followed, more or less explicitly, in taxonomic works of the 18th century, in an attempt to understand the status of capitalised epithets. We conclude that such epithets were viewed by their authors as nouns in apposition, or more rarely as nouns in the genitive. Therefore, nowadays, they must be treated as invariable, and not as adjectives that should agree in grammatical gender with the generic substantives with which they are combined. We provide a catalogue of these herpetological capitalised epithets in Linnaeus (1758, 1760) and Linné (1766–1767) with some nomenclatural consequences that result from our observations, especially for Corallus hortulana, Macrovipera lebetinus and Thamnophis saurita. In order to solve some nomenclatural cases, we had to resort to 12 Articles of the Code (1.3.1, 3, 11.9.1.2, 11.9.1.3, 23.2, 23.9, 31.1, 31A, 31.2.2, 32.5.1, 33.3.1, 34.2.1, 58) and to 29 technical nomenclatural terms. One more time, this highlights the fact that nomenclatural problems concerning old nomina cannot be properly dealt with in a hurry and without a good, but also critical, knowledge of the Code, and that the use of a more detailed terminology than that of the Code facilitates such a work.
Improved oral hygiene care is associated with decreased risk of occurrence for atrial fibrillation and heart failure: A nationwide population-based cohort study
Authors: Chang Yoonkyung , Woo Ho Geol , Park Jin , Lee Ji Sung , Song Tae-Jin 
Published: December 2019

Aims
Poor oral hygiene can provoke transient bacteremia and systemic inflammation, a mediator of atrial fibrillation and heart failure. This study aims to investigate association of oral hygiene indicators with atrial fibrillation and heart failure risk in Korea.

Methods
We included 161,286 subjects from the National Health Insurance System-Health Screening Cohort who had no missing data for demographics, past history, or laboratory findings. They had no history of atrial fibrillation, heart failure, or cardiac valvular diseases. For oral hygiene indicators, presence of periodontal disease, number of tooth brushings, any reasons of dental visit, professional dental cleaning, and number of missing teeth were investigated.

Results
During median follow-up of 10.5 years, 4911 (3.0%) cases of atrial fibrillation and 7971 (4.9%) cases of heart failure occurred. In multivariate analysis after adjusting age, sex, socioeconomic status, regular exercise, alcohol consumption, body mass index, hypertension, diabetes, dyslipidemia, current smoking, renal disease, history of cancer, systolic blood pressure, blood and urine laboratory findings, frequent tooth brushing (≥3 times/day) was significantly associated with attenuated risk of atrial fibrillation (hazard ratio: 0.90, 95% confidence interval (0.83–0.98)) and heart failure (0.88, (0.82–0.94)). Professional dental cleaning was negatively (0.93, (0.88–0.99)), while number of missing teeth ≥22 was positively (1.32, (1.11–1.56)) associated with risk of heart failure.

Conclusion
Improved oral hygiene care was associated with decreased risk of atrial fibrillation and heart failure. Healthier oral hygiene by frequent tooth brushing and professional dental cleaning may reduce risk of atrial fibrillation and heart failure.
The interaction effect between physical and cultural leisure activities on the subsequent decline of instrumental ADL: the Fujiwara-kyo study
Authors: Komatsu Masayo , Obayashi Kenji , Tomioka Kimiko , Morikawa Masayuki , Jojima Noriko , Okamoto Nozomi , Kurumatani Norio , Saeki Keigo 
Published: December 2019

Abstract
Background
Maintenance of instrumental activities of daily living (IADL) and social role (SR) is crucial to keep independent life because the decline in SR and IADL was a significant predictor of dependence in basic ADL in later. The independent effect of physical and cultural leisure activities and their effect modification on the IADL remains unknown.

Methods
We prospectively observed 3241 elderly with intact IADL at baseline for 5 years. Higher level functional capacity such as IADL and SR was assessed using the Tokyo Metropolitan Institute of Gerontology Index of competence (TMIG index).

Results
The mean age of the participants was 72.3 years (standard deviation 5.1), and 46.9% were male, and 90.9% of them received a follow-up assessment. Of the participants, 10.4% developed an IADL decline. Engagement in leisure physical activity was associated with a significantly lower risk of IADL decline (adjusted risk ratio, 0.73; 95% confidence interval [CI], 0.60 to 0.89), and cultural leisure activity was also associated with lower risk of IADL decline (adjusted risk ratio, 0.77; 95% CI, 0.63 to 0.95) independent of potential confounders. We also found significant and positive interaction between physical and cultural leisure activities at risk for IADL decline (P = 0.024) and SR decline (P = 0.004).

Conclusions
We found an independent association of physical and cultural leisure activities with a lower risk for functional decline in IADL and SR with positive interaction. Combined engagement in physical and cultural activities may effectively prevent from IADL decline and SR decline.
Evaluating the ecotoxicity of nitrification inhibitors using terrestrial and aquatic test organisms
Authors: Kösler Julia Elli , Calvo Olga C. , Franzaring Jürgen , Fangmeier Andreas 
Published: December 2019

Abstract
Background
The increasing demand for food and animal fodder worldwide has led to an intensified agriculture with an increasing use of nitrogen fertilizers. More recently, nitrate leaching and gaseous nitrogen emissions have become the focus of environmental discussions and climate politics. One approach to reduce such negative impacts is the use of nitrification inhibitors (NIs) that have shown to effectively reduce nitrogen losses to the groundwater and the air. However, ecotoxic effects of NIs have been studied to a limited extent only. Therefore, two commercial NIs (Piadin and Vizura) and an active ingredient of another NI, dicyandiamide (DCD), were assayed using various ecotoxicological biotests and test species: the Lemna Growth Inhibition Test (Lemna gibba), the Seed Germination/Root Elongation Toxicity Test (Agrostemma githago, Fagopyrum esculentum, Glycine max, Hordeum vulgare, Lunaria annua, Zea mays), the Seedling Emergence and Seedling Growth Test (A. githago, F. esculentum, Z. mays) and the marine Luminescent Bacteria Test (Aliivibrio fischeri). The fresh water L. gibba and the bacterium A. fischeri were exposed to different test concentrations in liquid growth media, whereas the terrestrial plants were exposed to the test substances diluted/dissolved in deionized water and added to the solid growth medium.

Results
Dicyandiamide did not show ecotoxic effects in any test conducted. Piadin and Vizura showed ecotoxic effects throughout all experiments. Frond number and frond area of L. gibba were inhibited with increasing concentrations of both substances with Piadin leading to an earlier inhibition and therefore lower EC50 values. In the Seed Germination Test, Vizura generally inhibited seed germination and root development more effectively than Piadin. Regarding both substances, the endpoint root length was much more sensitive than the endpoint germination. In the Seedling Emergence Test, Z. mays was the least sensitive and the rare weed species A. githago the most sensitive species with regard to the tested endpoints and both substances. A. fischeri was strongly inhibited by Vizura, whereas Piadin had barely effects on the bacteria.

Conclusion
All findings indicate ecotoxic effects of Piadin and Vizura, especially on the aquatic species L. gibba and on the root development of several terrestrial plant species. However, the origins of the ecotoxic properties remain unclear as both substances contain a mixture of—to some extent unknown—chemical compounds.
Intestinal microbiota domination under extreme selective pressures characterized by metagenomic read cloud sequencing and assembly
Authors: Kang Joyce B. , Siranosian Benjamin A. , Moss Eli L. , Banaei Niaz , Andermann Tessa M. , Bhatt Ami S. 
Published: December 2019

Abstract
Background
Low diversity of the gut microbiome, often progressing to the point of intestinal domination by a single species, has been linked to poor outcomes in patients undergoing hematopoietic cell transplantation (HCT). Our ability to understand how certain organisms attain intestinal domination over others has been restricted in part by current metagenomic sequencing technologies that are typically unable to reconstruct complete genomes for individual organisms present within a sequenced microbial community. We recently developed a metagenomic read cloud sequencing and assembly approach that generates improved draft genomes for individual organisms compared to conventional short-read sequencing and assembly methods. Herein, we applied metagenomic read cloud sequencing to four stool samples collected longitudinally from an HCT patient preceding treatment and over the course of heavy antibiotic exposure.

Results
Characterization of microbiome composition by taxonomic classification of reads reveals that that upon antibiotic exposure, the subject’s gut microbiome experienced a marked decrease in diversity and became dominated by Escherichia coli. While diversity is restored at the final time point, this occurs without recovery of the original species and strain-level composition. Draft genomes for individual organisms within each sample were generated using both read cloud and conventional assembly. Read clouds were found to improve the completeness and contiguity of genome assemblies compared to conventional assembly. Moreover, read clouds enabled the placement of antibiotic resistance genes present in multiple copies both within a single draft genome and across multiple organisms. The occurrence of resistance genes associates with the timing of antibiotics administered to the patient, and comparative genomic analysis of the various intestinal E. coli strains across time points as well as the bloodstream isolate showed that the subject’s E. coli bloodstream infection likely originated from the intestine. The E. coli genome from the initial pre-transplant stool sample harbors 46 known antimicrobial resistance genes, while all other species from the pre-transplant sample each contain at most 5 genes, consistent with a model of heavy antibiotic exposure resulting in selective outgrowth of the highly antibiotic-resistant E. coli.

Conclusion
This study demonstrates the application and utility of metagenomic read cloud sequencing and assembly to study the underlying strain-level genomic factors influencing gut microbiome dynamics under extreme selective pressures in the clinical context of HCT.
A hybrid self-attention deep learning framework for multivariate sleep stage classification
Authors: Yuan Ye , Jia Kebin , Ma Fenglong , Xun Guangxu , Wang Yaqing , Su Lu , Zhang Aidong 
Published: December 2019

Abstract
Background
Sleep is a complex and dynamic biological process characterized by different sleep patterns. Comprehensive sleep monitoring and analysis using multivariate polysomnography (PSG) records has achieved significant efforts to prevent sleep-related disorders. To alleviate the time consumption caused by manual visual inspection of PSG, automatic multivariate sleep stage classification has become an important research topic in medical and bioinformatics.

Results
We present a unified hybrid self-attention deep learning framework, namely HybridAtt, to automatically classify sleep stages by capturing channel and temporal correlations from multivariate PSG records. We construct a new multi-view convolutional representation module to learn channel-specific and global view features from the heterogeneous PSG inputs. The hybrid attention mechanism is designed to further fuse the multi-view features by inferring their dependencies without any additional supervision. The learned attentional representation is subsequently fed through a softmax layer to train an end-to-end deep learning model.

Conclusions
We empirically evaluate our proposed HybridAtt model on a benchmark PSG dataset in two feature domains, referred to as the time and frequency domains. Experimental results show that HybridAtt consistently outperforms ten baseline methods in both feature spaces, demonstrating the effectiveness of HybridAtt in the task of sleep stage classification.
A disease-related gene mining method based on weakly supervised learning model
Authors: Zhang Han , Huo Xueting , Guo Xia , Su Xin , Quan Xiongwen , Jin Chen 
Published: December 2019

Abstract
Background
Predicting disease-related genes is helpful for understanding the disease pathology and the molecular mechanisms during the disease progression. However, traditional methods are not suitable for screening genes related to the disease development, because there are some samples with weak label information in the disease dataset and a small number of genes are known disease-related genes.

Results
We designed a disease-related gene mining method based on the weakly supervised learning model in this paper. The method is separated into two steps. Firstly, the differentially expressed genes are screened based on the weakly supervised learning model. In the model, the strong and weak label information at different stages of the disease progression is fully utilized. The obtained differentially expressed gene set is stable and complete after the algorithm converges. Then, we screen disease-related genes in the obtained differentially expressed gene set using transductive support vector machine based on the difference kernel function. The difference kernel function can map the input space of the original Huntington’s disease gene expression dataset to the difference space. The relation between the two genes can be evaluated more accurately in the difference space and the known disease-related gene information can be used effectively.

Conclusions
The experimental results show that the disease-related gene mining method based on the weakly supervised learning model can effectively improve the precision of the disease-related gene prediction compared with other excellent methods.
Exploring the 2D and 3D structural properties of topologically associating domains
Authors: Liu Tong , Wang Zheng 
Published: December 2019

Abstract
Background
Topologically associating domains (TADs) are genomic regions with varying lengths. The interactions within TADs are more frequent than those between different TADs. TADs or sub-TADs are considered the structural and functional units of the mammalian genomes. Although TADs are important for understanding how genomes function, we have limited knowledge about their 3D structural properties.

Results
In this study, we designed and benchmarked three metrics for capturing the three-dimensional and two-dimensional structural signatures of TADs, which can help better understand TADs’ structural properties and the relationships between structural properties and genetic and epigenetic features. The first metric for capturing 3D structural properties is radius of gyration, which in this study is used to measure the spatial compactness of TADs. The mass value of each DNA bead in a 3D structure is novelly defined as one or more genetic or epigenetic feature(s). The second metric is folding degree. The last metric is exponent parameter, which is used to capture the 2D structural properties based on TADs’ Hi-C contact matrices. In general, we observed significant correlations between the three metrics and the genetic and epigenetic features. We made the same observations when using H3K4me3, transcription start sites, and RNA polymerase II to represent the mass value in the modified radius-of-gyration metric. Moreover, we have found that the TADs in the clusters of depleted chromatin states apparently correspond to smaller exponent parameters and larger radius of gyrations. In addition, a new objective function of multidimensional scaling for modelling chromatin or TADs 3D structures was designed and benchmarked, which can handle the DNA bead-pairs with zero Hi-C contact values.

Conclusions
The web server for reconstructing chromatin 3D structures using multiple different objective functions and the related source code are publicly available at http://dna.cs.miami.edu/3DChrom/.