Miracle-dz/UniFAR-FTUs huggingface dataset:
Clinical research on stereotactic radiosurgery combined with epithermal growth factor tyrosine kinase inhibitors in the treatment of brain metastasis of non-small cell lung cancer.

PURPOSE To compare the clinical efficacy and safety of stereotactic radiosurgery (SRS) combined with epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) versus whole-brain radiation therapy (WBRT) combined with EGFR-TKIs in the treatment of brain metastasis of non-small cell Lung cancer (NSCLC). METHODS The clinical data of patients with brain metastatic NSCLC who had EGFR-sensitive mutation and followed between January 2014 and January 2016 was retrospectively analyzed. Patients were divided into two groups according to their treatment types. Fifty seven patients were treated with SRS combined with EGFR-TKIs, while another 57 patients were treated with WBRT combined with EGFR-TKIs. The clinical efficacy, intracranial progression-free survival (iPFS), systemic progression-free survival (sPFS), overall survival (OS,) and adverse reactions were compared between the two groups. Computed tomography (CT) or magnetic resonance imaging (MRI) were used for imaging evaluation in both groups and all patients underwent symptomatic treatment such as dehydration or hormone therapy according to the patient's condition. The efficacy was evaluated using the Response Evaluation Criteria in Solid Tumors (RECIST) (Version 1.1) and adverse reactions were assessed based on the criteria for toxic reaction of anti-cancer drugs of WHO. RESULTS There were no statistically significant differences in general conditions between the two groups of patients. The median iPFS and median sPFS were similar between the two groups (12.2 months vs. 11.5 months and 10.7 months vs. 9.8 months respectively, p>0.05). The median OS of patients treated with SRS + EGFR-TKIs was significantly longer than in those treated with WBRT + EGFR-TKIs (25.1 months vs. 22.0 months, respectively, p=0.042). No statistically significant differences were found in the objective response rate (ORR), disease control rate (DCR), the incidence rates of cytopenia, gastrointestinal reaction and liver dysfunction between the two groups (p>0.05). There were 8 cases with radiotherapy-associated grade 3 or higher brain damage in SRS + EGFR-TKIs group compared to 19 cases in those treated with WBRT + EGFR-TKIs, suggesting that the incidence rate of radiation-induced brain injuries in SRS + EGFR-TKIs group was remarkably lower than those in WBRT + EGFR-TKIs group (p=0.026). CONCLUSION The clinical efficacy of SRS combined with EGFR-TKIs is comparable to that of WBRT combined with EGFR-TKIs in the treatment of NSCLC patients with ≤3 brain metastases and EGFR-sensitive mutation and the OS of patients is longer, with lower toxic side effect and higher safety, hence SRS combined with EGFR-TKIs should be used as the preferred therapeutic regimen.
Plasmid Involvement in Linalool Metabolism by Pseudomonas fluorescens

A bacterial strain was isolated from a wastewater lagoon and identified as Pseudomonas fluorescens. This isolate was able to utilize linalool as a sole carbon and energy source. The ability was found to be encoded on a 60-megadalton transmissible plasmid, pSRQ60. The plasmid was also mated into a commercial waste treatment strain, which expanded its ability to utilize other isoprenoid compounds.
Distribution and regulation of substance P‐related peptide in the frog visual system

Modulation of visual signal activity has consequences for both signal processing and for activity‐dependent structuring mechanisms. Among the neuromodulatory agents found in visual areas are substance P (SP)‐related peptides. This article reviews what is known about these substances in the amphibian retina and optic tectum with special emphasis on the leopard frog, Rana pipiens. It is found that the distribution of these SP‐related peptides is remarkably similar to that seen in mammals. This suggests that study of model amphibian systems may significantly enhance our understanding of how neuropeptides contribute to visual system function and organization. Microsc. Res. Tech. 54:220–228, 2001. © 2001 Wiley‐Liss, Inc.
Parasite resistance predicts fitness better than fecundity in a natural population of the freshwater snail Potamopyrgus antipodarum

The cost of males should give asexual females an advantage when in competition with sexual females. In addition, high‐fecundity asexual genotypes should have an advantage over low‐fecundity clones, leading to reduction in clonal diversity over time. To evaluate fitness components in a natural population, we measured the annual reproductive rate of individual sexual and asexual female Potamopyrgus antipodarum, a New Zealand freshwater snail, in field enclosures that excluded competitors and predators. We used allozyme genotyping to assign the asexual females to particular clonal genotypes. We found that the most fecund asexual clones had similar or higher fecundity as the top 10% of sexual families, suggesting that fecundity selection, even without the cost of males, would lead to replacement of the sexual population by clones. Consequently, we expected that the clones with the highest fecundity would dominate the natural population. Counter to this prediction, we found that high annual reproductive rates did not correlate with the frequency of clones in the natural population. When we exposed the same clones to parasites in the laboratory, we found that resistance to infection was positively correlated with the frequency of clones in the population. The correlation between fecundity and parasite resistance was negative, suggesting a trade‐off between these two traits. Our results thus suggest that parasite resistance is an important short‐term predictor of the success of asexual P. antipodarum in this population.
SPST-Index: A Self-Pruning Splay Tree Index for Caching Database Cracking

In database cracking, a database is physically self-organized into cracked partitions with cracker indices boosting the access to these partitions. The AVL Tree is the data structure of choice to implement cracker indices. However, it is particularly cache-inefficient for range queries, because the nodes accessed only for a few times (i.e, “Cold Data”) and the most accessed ones (i.e, “Hot Data”) are spread all over the index. In this paper, we present the Self-Pruning Splay Tree (SPST) data structure to index database cracking and reorganize “Hot Data” and “Cold Data” to boost the access to the cracked partitions. To every range query, the SPST rotates to the root the nodes pointing to the edges and to the middle value of the predicate interval. Eventually, the most accessed tree nodes remain close to the root improving CPU and cache activity. On the other hand, the least accessed tree nodes remain close to the leaves and are pruned to improve updates. Our experimental evaluation shows 37% more Instructions per Cycle and 75.9% less cache misses in L1 for lookup operations in the SPST compared to the AVL tree. Our data structure outperforms the AVL tree for lookups and maintenance costs in three major data access patterns: random, sequential and skewed. The SPST outperforms the AVL in 4% even in the worst case scenario with mixed workloads with lookups and batch updates.
Biological Rationale for Targeting MEK/ERK Pathways in Anti-Cancer Therapy and to Potentiate Tumour Responses to Radiation

ERK1 and ERK2 (ERKs), two extracellular regulated kinases (ERK1/2), are evolutionary-conserved and ubiquitous serine-threonine kinases involved in regulating cell signalling in normal and pathological tissues. The expression levels of these kinases are almost always different, with ERK2 being the more prominent. ERK1/2 activation is fundamental for the development and progression of cancer. Since their discovery, much research has been dedicated to their role in mitogen-activated protein kinases (MAPK) pathway signalling and in their activation by mitogens and mutated RAF or RAS in cancer cells. In order to gain a better understanding of the role of ERK1/2 in MAPK pathway signalling, many studies have been aimed at characterizing ERK1/2 splicing isoforms, mutants, substrates and partners. In this review, we highlight the differences between ERK1 and ERK2 without completely discarding the hypothesis that ERK1 and ERK2 exhibit functional redundancy. The main goal of this review is to shed light on the role of ERK1/2 in targeted therapy and radiotherapy and highlight the importance of identifying ERK inhibitors that may overcome acquired resistance. This is a highly relevant therapeutic issue that needs to be addressed to combat tumours that rely on constitutively active RAF and RAS mutants and the MAPK pathway.
Food insecurity is associated with anxiety, stress, and symptoms of posttraumatic stress disorder in a cohort of women with or at risk of HIV in the United States.

BACKGROUND Food insecurity, which disproportionately affects marginalized women in the United States, is associated with depressive symptoms. Few studies have examined relations of food insecurity with other mental health outcomes. OBJECTIVE The aim of this study was to investigate the associations of food insecurity with symptoms of generalized anxiety disorder (GAD), stress, and posttraumatic stress disorder (PTSD) in the Women's Interagency HIV Study (WIHS), a prospective cohort study of women with or at risk of HIV in the United States. METHODS Participants were 2553 women with or at risk of HIV, predominantly African American/black (71.6%). Structured questionnaires were conducted during April 2013-March 2016 every 6 mo. Food security (FS) was the primary predictor, measured using the Household Food Security Survey Module. We measured longitudinal outcomes for GAD (GAD-7 score and a binary GAD-7 screener for moderate-to-severe GAD). Only cross-sectional data were available for outcomes measuring perceived stress (PSS-10 score) and PTSD (PCL-C score and a binary PCL-C screener for PTSD). We examined associations of FS with the outcomes through use of multivariable linear and logistic regression, including lagged associations with GAD outcomes. RESULTS After adjusting for sociodemographic and health-related factors including HIV serostatus, current marginal, low, and very low FS were associated with increasingly higher GAD-7 scores, and with 1.41 (95% CI: 1.10, 1.80; P < 0.01), 2.03 (95% CI: 1.59, 2.61; P < 0.001), and 3.23 (95% CI: 2.43, 4.29; P < 0.001) times higher odds of screening positive for moderate-to-severe GAD, respectively. Low and very low FS at the previous visit (6 mo earlier) were independently associated with GAD outcomes at current visit. Associations of FS with PSS-10 and PCL-C scores exhibited similar dose-response relations. Very low FS was associated with 1.93 (95% CI: 1.15, 3.24; P < 0.05) times higher odds of screening positive for PTSD. CONCLUSIONS Food insecurity may be associated with a range of poor mental health outcomes among women in the United States with or at risk of HIV.
Inhibition of Corneal Fibrosis by Topical Application of Blocking Antibodies to TGFβ in the Rabbit

Previous studies have shown that TGFβ 1, induces activation and myofibroblast transformation of cultured rabbit corneal keratocytes. To determine whether TGFβ has a similar function in vivo, we evaluated the effect of TGFβ-blocking antibodies on corneal fibrosis after lamellar keratectomy (LK) in the rabbit. A total of 51 rabbits received standard LK wounds, and eyes were treated with 50 μl of Celluvisc/PBS, containing 10, 50, or UK) μg of 1DI1, a mouse monoclonal anti-TGFβ-blocking antibody. Control wounds received either 100 μg of an irrelevant mouse monoclonal antibody or vehicle alone. At days 14, 28, 42, and 56, eyes were evaluated by in vivo confocal microscopy (CM) and the mice were killed for light microscopy (LM) and immunostaining with antibodies to human fibronectin. In vivo CM of LK wounds clearly identified a disorganized layer that contained irregularly arranged fibroblasts and reflective extracellular matrix overlying normal corneal stroma. In a subset of 11 eyes stained with 5-(4,6-dichlorotriazinyl) aminofluorescein (DTAF) immediately after injury, the thickness of the disorganized layer identified by in vivo CM significantly correlated with both anterior corneal fibrosis (r= 0.627; p < 0.025) and depth of keratocyte activation (r = 0.8980; p < 0.0005), indicating that in vivo CM can be used quantitatively to assess anterior stromal fibrosis. In eyes treated with an irrelevant monocloncal antibody, in vivo corneal fibrosis averaged 100±26 (μm thick at day 14, whereas treatment with 10, 50, and 100 μg anti-TGFβ significantly reduced (p < 0.0005) the anterior disorganization in a dose-dependent fashion to 101 ± 32, 45 ± 11, and 56 ± 18 μm, respectively. Semiquantitative measurement of anti-fibronectin staining within the wound revealed that anti-TGFβ significantly reduced the intensity of anti-fibronectin staining in the anterior 50 μm of the corneal stroma (p < 0.003). These findings indicate that TGFβ plays an important in vivo role in keratocyte activation and myofibroblast transformation. Furthermore, the in vivo use of TGFβ-blocking antibody effects may allow modulation of corneal fibrosis after refractive surgery.
Dynamics in plant roots and shoots minimise stress, save energy and maintain water and nutrient uptake.

Plants are inherently dynamic. Dynamics minimise stress while flexibly acquiring resouces. Three examples are presented for plants tolerating saline soil: transport of NaCl, water and macronutrients is non-uniform along a branched root, visualised by mapping expressions with tissues and age; water and NaCl redistribute between shoot and soil at nighttime; and ATP for salt exclusion is much lower in thinner branch than main roots, quantified using a biophysical model and geometry from anatomy. Non-invasive phenotyping and precision agriculture technologies can be used together to harness dynamics, but analytical methods are needed. A plant advancing in time through a soil and atmosphere space is proposed as a framework for dynamic data and their relationship to crop improvement. This article is protected by copyright. All rights reserved.
The Phenomenology of Parkinson's Disease

Abstract The motor symptoms of Parkinson's disease are not limited to the cardinal symptoms of bradykinesia, rigidity, and resting tremor, but also include a variety of interrelated motor phenomena such as deficits in spatiotemporal planning and movement sequencing, scaling and timing of movements, and intermuscular coordination that can be clinically observed. Although many of these phenomena overlap, a review of the full breadth of the motor phenomenon can aid in the diagnosis and monitoring of disease progression.
Osteoblast response to nanostructured and phosphorus-enhanced titanium anodization surfaces

Titanium surface modification by anodization has been shown to promote bone formation. However, interactions between anodized layers and bone cells depend upon the anodized layer surface composition and morphology. The present study evaluated the effect of anodized layer phosphorus content, crystallinity, surface porosity, and roughness on the MC3T3-E1 osteoblast response. Commercially pure titanium specimens were anodized in two mixed-acid electrolytes to final forming voltages of 108 V and 180 V. The oxide crystallinity, surface porosity, surface roughness, and elemental composition of each specimen type were determined by X-ray diffraction, scanning electron microscopy, atomic force microscopy, and energy dispersive spectroscopy analyses. Osteoblast-like MC3T3-E1 cell attachment, proliferation, differentiation, and mineralization were assessed using optical and fluorescence microscopy, total protein content, alkaline phosphatase activity, osteocalcin production, and alizarin red assays. Oxide crystallinity and surface roughness increased with anodization forming voltage in each electrolyte. Phosphorus (P) uptake increased with forming voltage in the phosphoric acid containing electrolyte. The total protein assay showed P-incorporated, low surface pore density oxides to exhibit initially delayed proliferation compared to non-P containing high surface pore density oxides. Alkaline phosphatase and osteocalcin assays showed trends of early differentiation and maturation for P-incorporated, low surface pore density oxides compared to non-P containing high surface pore density oxides. Highly crystalline anodized layers were shown to induce enhanced mineralization compared to non-anodized titanium specimens. Overall, the biochemical influence of P-incorporation into the oxide layers showed trends of earlier osteoblast differentiation and maturation. The combination of P-incorporation, an anatase phase oxide, a low surface pore density, and a high surface roughness showed the highest mineralization levels.
Multifunctional graphene supports for electron cryomicroscopy

Significance Single-particle electron cryomicroscopy (cryoEM) has now proved to be the method of choice for determining the structure of biological macromolecules and complexes. Yet success in determining a structure by cryoEM depends on being able to prepare a frozen specimen on a small metal support called a grid. This process is poorly controlled at present because of molecule–surface interactions. Here we used a modified form of graphene, in conjunction with a stable grid made of gold, to control these surface effects. Functionalized graphene-on-gold grids improve the reliability of specimen preparation and enhance image quality. This technology has the potential to take specimen preparation for cryoEM from a trial and error art to a controlled and reproducible process. With recent technological advances, the atomic resolution structure of any purified biomolecular complex can, in principle, be determined by single-particle electron cryomicroscopy (cryoEM). In practice, the primary barrier to structure determination is the preparation of a frozen specimen suitable for high-resolution imaging. To address this, we present a multifunctional specimen support for cryoEM, comprising large-crystal monolayer graphene suspended across the surface of an ultrastable gold specimen support. Using a low-energy plasma surface modification system, we tune the surface of this support to the specimen by patterning a range of covalent functionalizations across the graphene layer on a single grid. This support design reduces specimen movement during imaging, improves image quality, and allows high-resolution structure determination with a minimum of material and data.
Structural and photosynthetic re-acclimation to low light in C4 maize leaves that developed under high light.

BACKGROUND AND AIMS C4 plants have higher photosynthetic capacity than C3 plants, but this advantage comes at an energetic cost that is problematic at low light. In the crop canopy, lower leaves first develop under high light but later experience low light because of mutual shading. To explore the re-acclimation of C4 leaves to low light, we investigated the structural and physiological changes of the leaves of maize plants grown in shaded pots. METHODS Plants were first grown under high light, and then some of them shaded (20% of sunlight) for three weeks. Four types of leaves were examined: new leaves that developed under low light during shading (L), new leaves that developed under high light (H), mature leaves that developed under high light before shading and were then subjected to low light (H-L), and mature leaves that always experienced high light (H-H). KEY RESULTS The leaf mass per area, nitrogen and chlorophyll contents per unit leaf area, chlorophyll a/b ratio, and activities of C3 and C4 photosynthetic enzymes were lower in H-L than in H-H leaves and in L than H leaves. Unlike L leaves, H-L leaves maintained the thickness and framework of the Kranz anatomy of H leaves, but chloroplast contents in H-L leaves were reduced. This reduction of chloroplast contents was achieved mainly by reducing the size of chloroplasts. Although grana of mesophyll chloroplasts were more developed in L leaves than in H leaves, there were no differences between H-L and H-H leaves. The light curves of photosynthesis in H-L and L leaves were very similar and showed traits of shade leaves. CONCLUSIONS Mature maize leaves that developed under high light re-acclimate to low-light environments by adjusting their biochemical traits and chloroplast contents to resemble shade leaves but maintain the anatomical framework of sun leaves.
Addition of taxanes to combination chemotherapy in distal intestinal gastric cancer is more beneficial than proximal ones: A multicenter retrospective study of Turkish Oncology Group.

PURPOSE Advanced gastric cancer has a dismal prognosis. Platin/5-fluorouracil (PF) combination chemotherapy is the main treatment modality for metastatic gastric cancer patients. Third drug addition to PF is a controversial issue. The aim of this study was to evaluate the predictive role of tumor localization and histopathology on choosing three- or two-drug combination regimens. METHODS This study was designed as a hospital-based retrospective observational case-series study. A total of 516 patients with advanced gastric cancer has been treated at eight different oncology centers in Turkey between 2006 and 2016. Laboratory results and demographic data were collected and analyzed. RESULTS The median patient age was 59 years (range 25-85). Proximal intestinal and distal intestinal cancers were found in 357 (69.2 %) and 159 (30.8 %) patients, respectively. 5-fluorouracil (5FU) and cisplatin (PF) and cisplatin+5FU+docetaxel (PFtax, also known as DCF) were administered to 240 (46.5%) and 276 (53.5%) patients, respectively. Median progression free survival (PFS) was 5.0 (95% CI 4.21-5.29) and 8 months (95% CI 7.22-8.77) for PF and PFtax groups, respectively (p=0.000). When tumor localization was used as stratum in PFS survival, PFtax produced significantly higher PFS rates only in distal intestinal type gastric cancer compared to PF (p=0.000). Median overall survival (OS) was 12 (95% CI 9.8-14.2) and 16 months (95% CI 13.6-18.4) for the PF and PFtax groups, respectively (p=0.01). When tumor localization was used as stratum in OS, PFtax showed significantly higher OS rates only in the distal intestinal type gastric cancer compared to PF (p=0.01) Conclusion: Pathology and tumor location in gastric cancer may affect the outcome. Addition of taxanes as a third drug may significantly increase PFS and OS rates only in distal intestinal type gastric cancer but not in patients with proximal type gastric cancer.
VCF‐Server: A web‐based visualization tool for high‐throughput variant data mining and management

Next‐generation sequencing (NGS) has been widely used in both clinics and research. It has become the most powerful tool for diagnosing genetic disorders and investigating disease etiology through the discovery of genetic variants. Variants identified by NGS are stored in variant call format (VCF) files. However, querying and filtering VCF files are extremely difficult for researchers without programming skills. Furthermore, as the mutation data are increasing exponentially, there is an urgent need to develop tools to manage these variant data in a centralized way.