gebhart/patrepeval huggingface dataset:
Identification of clinical variables and biomarkers of hypercoagulability for VTE risk evaluation in ambulatory patients with lung adenocarcinoma on chemotherapy: The ROADMAP study. (2016)

e23073 Background: In ambulatory patients with lung adenocarcinoma (LA) the risk of VTE increases during chemotherapy (CTx). The identification of clinically relevant biomarkers of hypercoagulability (BH) and clinical variables could lead to better evaluation of VTE risk. The prospective longitudinal non interventional study ROADMAP, was designed to identify the most relevant related risk factors of VTE in ambulatory patients with LA on CTx. Methods: Patients were included and followed up at 3, 6 and 12 months. Documented symptomatic VTE was the end-point of the study. Blood samples were collected at inclusion and assessed for BH (Table). Assays and reagents were from Stago (France). A Clinical Research Form was completed by patients' interview at inclusion. Univariate analysis was done. Results: The study included 150 patients (mean age 65 years, 73% male). The LA diagnosis was done within 6 months before inclusion in 70% of them and 90% had advanced or metastatic disease at inclusion. In 85% of patients the ECOG performance status was < 3. In one year follow up 12 symptomatic VTE episodes occurred (8%), 75% of which occurred within the 3 months from inclusion. The univariate analysis identified the odds ratio for each variable as shown in the table. Conclusions: The ROADMAP study reveals that the Mean Rate index (MRI) and the Procoagulant Phospholipid clotting time (PPL-ct) are the BH related with the risk of VTE in ambulatory patients with LA. Their combination with the clinically relevant variables of patients and cancer related VTE risk may build a RAM specific for this group of cancer patients. Odds Ratio (95% CI) Biomarkers Tissue factor activity (TFa) 0.991 (0.91 - 1.079) D-Dimers 0.917 (0.634 - 1.325) * Fibrin Monomers 0.983 (0.929 - 1.041) PPL-ct 1.058 (1.008 - 1.144) * Lag-time 0.603 (0.294 - 1.235) MRI 1.016 (1.003 - 1.032) * Peak 1.006 (0.997 - 1.016) ETP 1 ttPeak 0.522 (0.307 - 0.887) Clinical variables Recent hospitalization within the last month before assessment 4.274 (0.946 – 1.333)* Time since diagnosis of the cancer 4.679 (0.443 – 29.4) * Cancer progression 4.114 (1.014 - 16.692)* *p < 0.05
Replication of Genetic Markers Associated with Clozapine-Induced Agranulocytosis. (2006)

Abstract Clozapine is a highly efficacious drug for the treatment of schizophrenia, but its use is limited, in part due to the side effect of agranulocytosis. In order to reduce the incidence of clozapine-induced agranulocytosis (CIA), patients are required to submit to a blood monitoring program. A genetic component to CIA is suggested by published associations in a number of genes. A genetic test assessing the risk of CIA might allow safer and more broad use of clozapine. We previously conducted a candidate gene-based case-control study to discover genes associated with CIA. Cases were patients with an ANC&amp;lt;500 during clozapine treatment, and controls were patients treated for at least one year without a significant reduction in WBC or ANC. For each case, we attempted to enroll 2 age-, gender- and ethnicity-matched controls. We collected blood, medical histories and informed consent from 33 CIA cases and 54 controls. Seventy-four candidate genes were sequenced in the exons, intron-exon boundaries, 5′ untranslated region and promoter region for each of the cases and controls, and a haplotype analysis was conducted using logistic regression. A total of 20 haplotype markers in HLA-DQB1, 1 in HLA-C, 1 in NTSR1, 1 in DRD1 and 6 in CSF2RB were significant with permutation test adjusted p-values under 0.05. A replication analysis was performed on an independently collected cohort of 49 cases and 78 controls from Germany. Cases were patients who developed an ANC&amp;lt;500 during clozapine treatment, and controls were patients treated for at least two years without an adverse effect on the WBC or ANC. We attempted to replicate 28 haplotype markers from 4 of the 5 genes. We did not attempt to replicate the findings from HLA-C. Permutation tests were performed for markers within genes, and the Benjamini-Hochberg FDR method was applied to the best permutation p-values from the four genes. Markers with p-values less than 0.05 after these adjustments were considered replicated. One genetic marker in HLA-DQB1 replicated further implicating this as the strongest genetic association with CIA. Markers in CSF2RB were not statistically significant, but warrant further study. The strength of the findings is sufficient to develop a diagnostic test for CIA risk. These findings may also be applicable to agranulocytosis and neutropenia induced by other drugs.
In Situ Force Distribution in the Glenohumeral Joint Capsule during Anterior-Posterior Loading (2000)

JBJS was founded by the American Orthopaedic Association in 1903 and is the Official Journal of the American Orthopaedic Association. EXCELLENCE THROUGH PEER REVIEW The Journal of Bone & Joint Surgery (JBJS) has been the most valued source of information for orthopaedic surgeons and researchers for over 125 years and is the gold standard in peer-reviewed scientific information in the field. A core journal and essential reading for general as well as specialist orthopaedic surgeons worldwide, JBJS publishes evidence-based research to enhance the quality of care for orthopaedic patients. Standards of excellence and high quality are maintained in everything we do, from the science of the content published to the customer service we provide. JBJS is an independent, non-profit journal. JBJS.org is the version of record of The Journal of Bone & Joint Surgery. JBJS is published twice a month on the first and third Wednesday of each month, each time adding to a comprehensive PDF archive dating back to 1889. Additional features online include: article commenting, social sharing links, instructional videos, podcasts, and continuing medical education activities. Contributions from anywhere in the world are welcome and considered on their merits. The manuscript must be written in English and should be submitted as outlined in the Instructions for Authors. Manuscripts are subject to blinded peer review by experts and a final decision by the editor. Papers are judged by the quality and relevance of the work. Our aim is to publish the best material available from anywhere in the world.
Binding prediction of multi-domain cellulases with a dual-CNN (2022)

Cellulases hold great promise for the production of biofuels and biochemicals. However, they are modular enzymes acting on a complex heterogeneous substrate. Because of this complexity, the computational prediction of their catalytic properties remains scarce, which restricts both enzyme discovery and enzyme design. Here, we present a dual-input convolutional neural network to predict the binding of multi-domain enzymes. This regression model outperformed previous molecular dynamics-based methods for binding prediction for cellulases in a fraction of the time. Also, we show that when changed to a classification problem, the same network can be back-propagated to suggest mutations to improve enzyme binding. A similar approach could increase our understanding of the structure-activity relationship of enzymes, and suggest new promising mutations for enzyme design using explainable artificial intelligence.
Proteomic changes induced by harmine in human brain organoids reveal signaling pathways related to neuroprotection (2021)

Abstract Harmine is a β-carboline found in Banisteriopsis caapi , a constituent of ayahuasca brew. Ayahuasca is consumed as a beverage in native Americans’ sacred rituals and in religious ceremonies in Brazil. Throughout the years, the beneficial effects of ayahuasca to improve mental health and life quality have been reported, which propelled the investigation of its therapeutic potential to target neurological disorders such as depression and anxiety. Indeed, antidepressant effects of ayahuasca have been described, raising the question of which cellular mechanisms might underlie those effects. Previous animal studies describe potential neuroprotective mechanisms of harmine, including anti-inflammatory and antioxidant activities, and neurotrophin signaling activation. However, the cellular and molecular mechanisms modulated by harmine in human models remain less investigated. Here we analyzed the short-term changes in the proteome of human brain organoids treated with harmine using shotgun mass spectrometry. Harmine upregulates proteins related to synaptic vesicle cycle, cytoskeleton-dependent intracellular transport, cell cycle, glucose transporter-4 translocation, and neurotrophin signaling pathway. In addition, protein expression levels of Akt and phosphorylated CREB were increased after 24 hour-treatment. Our results shed light on the potential mechanisms that may underlie harmine-induced neuroprotective effects.
WE-F-16A-02: Design, Fabrication, and Validation of a 3D-Printed Proton Filter for Range Spreading (2014)

Purpose: To design, fabricate and test a 3D-printed filter for proton range spreading in scanned proton beams. The narrow Bragg peak in lower-energy synchrotron-based scanned proton beams can result in longer treatment times for shallow targets due to energy switching time and plan quality degradation due to minimum monitor unit limitations. A filter with variable thicknesses patterned on the same scale as the beam's lateral spot size will widen the Bragg peak. Methods: The filter consists of pyramids dimensioned to have a Gaussian distribution in thickness. The pyramids are 2.5mm wide at the base, 0.6 mm wide at the peak, 5mm tall, and are repeated in a 2.5mm pseudo-hexagonal lattice. Monte Carlo simulations of the filter in a proton beam were run using TOPAS to assess the change in depth profiles and lateral beam profiles. The prototypes were constrained to a 2.5cm diameter disk to allow for micro-CT imaging of promising prototypes. Three different 3D printers were tested. Depth-doses with and without the prototype filter were then measured in a ~70MeV proton beam using a multilayer ion chamber. Results: The simulation results were consistent with design expectations. Prototypes printed on one printer were clearly unacceptable on visual inspection. Prototypes on a second printer looked acceptable, but the micro-CT image showed unacceptable voids within the pyramids. Prototypes from the third printer appeared acceptable visually and on micro-CT imaging. Depth dose scans using the prototype from the third printer were consistent with simulation results. Bragg peak width increased by about 3x. Conclusions: A prototype 3D printer pyramid filter for range spreading was successfully designed, fabricated and tested. The filter has greater design flexibility and lower prototyping and production costs compared to traditional ridge filters. Printer and material selection played a large role in the successful development of the filter.
40% slope efficiency in a waveguide dye laser using a random active layer (2006)

We have demonstrated a waveguide dye laser including a thin active random layer. Use of thin film containing nano-size particles as well as laser dye (random active layer) is a promising solution to improve the efficiency. In this paper, we report a full characterization of the device parameters. We also demonstrated a low-threshold, highly efficient distributed feedback dye laser using an active random scattering media. And the slope efficiency of 38.5% and threshold of 0.96 muJ have achieved, respectively. This device has the ability that can be applied for the laser spectroscopy
Predicting Outcomes of Traumatic Brain Injury by Imaging Modality and Injury Distribution (2009)

Early prediction of outcomes after traumatic brain injury (TBI) is often difficult. To improve prognostic accuracy soon after trauma, we compared different radiological modalities and anatomical injury distribution in a group of adult TBI patients. The four methods studied were computed tomography (CT), magnetic resonance imaging (MRI) with T2-weighted imaging (T2WI), fluid-attenuated inversion recovery (FLAIR) imaging, and susceptibility weighted imaging (SWI). The objective of this study was to identify which modality and anatomic model best predict outcome. The patient population consisted of 38 adults admitted between February 2001 and May 2003. Early CT, T2WI, FLAIR, and SWI were obtained for each patient as well as a Glasgow Outcome Score (GOS) between 0.1 and 22 months (mean 9.2 months) after injury. Using a semi-automated computer method, intraparenchymal lesions were traced, measured, and converted to lesion volumes based on slice thickness and pixel size. Lesions were assigned to zones and regions. Outcomes were dichotomized into good (GOS 4-5) and poor (GOS 1-3) outcome groups. Brain injury detected by imaging was analyzed by median total lesion volume, median volume per lesion, and median number of lesions per outcome group. T2WI and FLAIR imaging most consistently discriminated between good and poor outcomes by median total lesion volume, median volume per lesion, and median number of lesions. In addition, T2WI and FLAIR imaging most consistently discriminated between good and poor outcomes by zonal distribution. While SWI rarely discriminated by outcome, it was very sensitive to intraparenchymal injury and its optimal use in evaluating TBI is unclear. SWI and other new imaging modalities should be further studied to fully evaluate their prognostic utility in TBI evaluation.
Differential immunostaining of various types of breast carcinomas for growth hormone‐releasing hormone receptor – Apocrine epithelium and carcinomas emerging as uniformly positive (2014)

Different classes of breast cancers were explored for their positivity for growth hormone-releasing hormone receptors (GHRH-R) in this pilot study, as no systematic evaluation of such tumors has been performed to date. Seventy-two small primary breast carcinomas were evaluated for GHRH-R expression by immunohistochemistry using a polyclonal antibody and a cutoff value of 10% staining. GHRH-R positivity was detected in 58% of all cases, 20/23 (87%) of invasive lobular carcinomas (ILC) and 22/46 (48%) of invasive ductal carcinomas (IDC). GHRH-R positivity was more frequent in grade 2 tumors (86%), as compared to grade 1 (18%) or grade 3 (47%) cancers. GHRH-R expression was not associated with mitotic scores, the Ki-67 labeling indices or nodal status. IDCs with casting-type calcifications on the mammogram showed positivity for GHRH-R in 9/12 (75%) cases. Most importantly, apocrine epithelium, and all 10 apocrine carcinomas added later to the study were GHRH-R-positive. These preliminary results suggest a greater than average GHRH-R expression in ILCs and IDCs associated with casting-type calcifications on the mammogram. Apocrine carcinomas seem uniformly positive for GHRH-R. Whether these findings could indicate a potential role of GHRH-antagonists in targeted treatment of these types of breast cancer requires further studies.
Optimisation and integration of membrane processes in the beverage industry (2005)

Potential applications of membrane technology for the beverage industry will be presented by two case studies. The focus of the first case study is on the clarification and concentration of fruit juice. A novel combination of a centrifuge with ultrafiltration for the clarification will be discussed together with the combination of an evaporator combined with reverse osmosis for the concentration. The second case study will highlight the potentials of microfiltra-tion to recovery beer from tank bottoms. Both case studies will be evaluated from a technical and economical point of view.
Deterministic generation and switching of dissipative Kerr soliton in a thermally controlled micro-resonator (2018)

Dissipative Kerr solitons (DKSs) in the high-Q micro-resonator corresponds to self-organized short pulse in time domain via double balance between dispersion and Kerr nonlinearity, as well as cavity loss and parametric gain. In this paper, we first experimentally demonstrate deterministic generation and switching of DKSs in a thermally controlled micro-ring resonator based on high-index doped silica glass platform. In our scheme, an auxiliary laser is introduced to timely balance the intra-cavity heat fluctuation. By decreasing the operating temperature through a thermo-electric cooler, soliton crystal is firstly generated, then increasing the temperature, DKSs switching and single soliton are robustly accessed, which is independent of the tuning speed. During the switching process, varieties of DKSs are identified by tens of featured discrete soliton-steps, which is favorable for study of on-chip soliton interactions and nonlinear applications.
The effect of apolipoprotein(a)-, apolipoprotein E-, and apolipoprotein A4- polymorphisms on quantitative lipoprotein(a) concentrations (2000)

The effects of apolipoprotein (a), apolipoprotein-E, and apolipoprotein-A4 isoforms on quantitative lipoprotein(a) [Lp(a)] levels were assessed in a sample of 142 Dutch families consisting of two parents and their adolescent twin offspring. A total heritability of 95% was estimated for plasma Lp(a) concentrations. The largest part of this heritability was due to the apo(a) locus which explained 61% of the total variance in Lp(a) levels. The pattern of familial correlations for the residual part of the Lp(a) variance that could not be attributed to the apo(a) isoforms, suggested genetic influences on the residual variance. We addressed the question whether this residual genetic variance could be ascribed to the apoE or the apoA4 locus. A simultaneous analysis of all three loci showed that both the apoE and the apoA4 polymorphism did not contribute significantly to Lp(a) variation.
ChemInform Abstract: 2‐Alkyl‐Substituted Histamines and Hydroxyethylimidazoles with G‐ Protein‐Stimulatory Activity. (1996)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
External downscaling of the ascending aorta, supraaortic debranching and aortic stent grafting for extensive aortic arch aneurysm treatment (2009)

Objective: Replacement of the ascending aorta, aortic arch and proximal descending aorta using CPB/hypothermic circulatory arrest (HCA) for aneurysms involving these segments can be performed with low morbidity/mortality in specialised centres. However, in elderly patients with comorbidities the perioperative risk is significantly increased. An alternative treatment mode is described.
Heterotrimeric G-protein α subunit (RGA1) regulates tiller development, yield, cell wall, nitrogen response and biotic stress in rice (2021)

G-proteins are implicated in plant productivity, but their genome-wide roles in regulating agronomically important traits remain uncharacterized. Transcriptomic analyses of rice G-protein alpha subunit mutant (rga1) revealed 2270 differentially expressed genes (DEGs) including those involved in C/N and lipid metabolism, cell wall, hormones and stress. Many DEGs were associated with root, leaf, culm, inflorescence, panicle, grain yield and heading date. The mutant performed better in total weight of filled grains, ratio of filled to unfilled grains and tillers per plant. Protein-protein interaction (PPI) network analysis using experimentally validated interactors revealed many RGA1-responsive genes involved in tiller development. qPCR validated the differential expression of genes involved in strigolactone-mediated tiller formation and grain development. Further, the mutant growth and biomass were unaffected by submergence indicating its role in submergence response. Transcription factor network analysis revealed the importance of RGA1 in nitrogen signaling with DEGs such as Nin-like, WRKY, NAC, bHLH families, nitrite reductase, glutamine synthetase, OsCIPK23 and urea transporter. Sub-clustering of DEGs-associated PPI network revealed that RGA1 regulates metabolism, stress and gene regulation among others. Predicted rice G-protein networks mapped DEGs and revealed potential effectors. Thus, this study expands the roles of RGA1 to agronomically important traits and reveals their underlying processes.
Numerical modeling to analysis the abrasion of knee joint by walking pattern (2017)

In current studies, growing up of treatment of the knee joint damage such as arthritis, the research to prevent knee joint is under way. As knee joints could be damaged by various types of motion, one of the most influential factor of the abrasion on the knee joint is progressed by walking. It could be classified as 3 types of walking, 1. Walking plain, 2. Climbing stairs or uphill and 3. Going down. In this study, to find the damaged point of knee joint, the following ways would be used. After comparing the knee joint angle with interior and exterior movement of the knee in accordance with the joint dynamics of typical height, the walking pattern for walking up the stairs can be comprehended. It could be shown the variation of the center of rotation of knee joint. From this, the contact point which is pressed on the knee joints in accordance with each walking pattern could be derived. The numerical modeling could be made by quantifying the variety that is caused by the center of mass of knee bone. It would be expected to calculate the contact point on the knee joint through walking patterns. This numerical model is considered of the kinematics system in our knee.
Phenytoin (1979)

The electroencephalographic (EEG) and behavioral effects of oral doses of phenytoin from 100 mg to 1 g in normal male volunteers were measured. The electroencephalogram exhibited decreases in power in the slow frequencies and increases in the fast frequencies, accompanied by an increase in mean frequency. These changes are similar to those seen with psychostimulants. They occurred at average plasma levels of 8 micrograms/ml and above. The time course and the intensity of EEG effects parallel plasma levels. Drug-related EEG changes were bilaterally symmetric. EEG changes at plasma levels of 8--12 micrograms/ml were not associated with behavioral toxic signs. These findings suggest that future psychiatric studies of phenytoin as a psychostimulant should include monitoring for plasma levels, with a minimum of 8 micrograms/ml as a guide to clinical efficacy.
Comparison of MS<sup>2</sup>-Only, MSA, and MS<sup>2</sup>/MS<sup>3</sup> Methodologies for Phosphopeptide Identification (2008)

Current mass spectrometers provide a number of alternative methodologies for producing tandem mass spectra specifically for phosphopeptide analysis. In particular, generation of MS(3) spectra in a data-dependent manner upon detection of the neutral loss of a phosphoric acid in MS(2) spectra is a popular technique for circumventing the problem of poor phosphopeptide backbone fragmentation. The newer Multistage Activation method provides another option. Both these strategies require additional cycle time on the instrument and therefore reduce the number of spectra that can be measured in the same amount of time. Additional informatics is often required to make most efficient use of the additional information provided by these spectra as well. This work presents a comparison of several commonly used mass spectrometry methods for the study of phosphopeptide-enriched samples: an MS(2)-only method, a Multistage Activation method, and an MS(2)/MS(3) data-dependent neutral loss method. Several strategies for dealing effectively with the resulting MS(3) data in the latter approach are also presented and compared. The overall goal is to infer whether any one methodology performs significantly better than another for identifying phosphopeptides. On data presented here, the Multistage Activation methodology is demonstrated to perform optimally and does not result in significant loss of unique peptide identifications.