jimnoneill/paper-to-field-training huggingface dataset:
In vitro investigation of trans SNARE complexes arrested between artifical membranes.

The key components of the machinery that catalyzes membrane fusion include membrane-associated small proteins that are termed as soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs). Calcium-triggered synaptic vesicle exocytosis is one of the most investigated SNARE-mediated fusion processes. Three synaptic SNARE proteins zipper into ternary complexes from their membrane-distant N-termini towards their membrane proximal C-termini. This assembly drives the merger of the synaptic vesicles with the pre-synaptic membrane. After the exocytosis, ternary complexes are disassembled into reactivated monomers for subsequent rounds of neurotransmitter release. This cycle includes a transient assembly intermediate that forms as the synaptic vesicle SNARE (synaptobrevin) starts zippering with the pre-synaptic plasma membrane SNAREs (syntaxin and SNAP-25). Prior to membrane fusion, partially zippered SNARE complexes are found in trans configurations with the transmembrane domains of synaptobrevin and syntaxin residing in two opposing membranes. These complexes are the substrates of various regulatory factors that control the calcium-triggered release process tightly. Current models of this regulation are based on the indirect measurements of membrane fusion probes. It was not possible so far to address the protein-protein interactions directly due to difficulties in isolating the short-lived trans SNARE complexes. This study presents a biochemically well-defined reconstitution system that captures such trans complexes successfully. SNARE zippering was artificially arrested between docking, but not-fusing large liposomes (diameter, 100 nm) by using mutants of synaptobrevin. The disassembly machinery (NSF and α-SNAP) and tetanus neurotoxin were effectively incorporated into this system. Several biochemical assays were developed utilizing these factors to study the characteristics of the trans complexes. The assembly and disassembly cycles of the trans SNARE complexes were monitored directly via fluorescently labeled proteins or indirectly via fluorescently labeled lipids. These measurements were extremely helpful in deducing the extent of SNARE zippering. Each of the two synaptobrevin mutants was involved in very different trans configurations depending on the region where their zippering was arrested, one being loosely and the other being tightly zippered. These advances proved this reconstitution system as an ideal medium for further investigations. It is made possible to address the key steps that regulate the progression from loose to tight zippering directly. Understanding this regulation is crucial for elucidating the step-wise mechanisms that attain high accuracy and speed in synaptic transmission.

Topic: Lipid Membrane Structure and Behavior
Subfield: Molecular Biology
Field: Biochemistry, Genetics and Molecular Biology
Domain: Life Sciences
Evaluation of Catheter-Directed Thrombolysis Device Type and Dosing on Treatment Outcomes in Intermediate-Risk Pulmonary Embolism: A Randomized Controlled Trial Post Hoc Analysis.

Purpose To assess if catheter-directed thrombolysis (CDT) treatment heterogeneity in the multicenter [REDACTED] RCT is associated with differences in pulmonary embolism (PE) clinical outcomes. Materials And Methods All [REDACTED] CDT arm patients were eligible for post hoc analysis, excluding those treated with multiple CDT device types (n=8), non-tPA thrombolytics (n=10), or pharmacomechanical CDT (n=12). Patients were grouped by treatment: ultrasound-accelerated CDT (USAT) or standard CDT (SCDT). Treatment protocols were assessed, and clinical, safety, and quality-of-life outcomes were compared at discharge/7 days, 24 hours, and/or 30 days. Results 159 USAT and 87 SCDT patients were included. Longer mean treatment duration (12.4 vs 20.8 hours, p&lt;0.001), higher mean thrombolytic dose (17.2 vs 23.4mg tPA, p&lt;0.001), and more ICU stays &gt;24 hours (57.4% vs 80.5%, p&lt;0.001) were identified in the SCDT group. However, in-hospital outcomes were not different, including all-cause mortality (0.0% vs 1.1%, p=0.35), intracranial hemorrhage (0.6% vs 0.0%, p=1.00), major bleeding (5.7% vs 10.3%, p=0.20), and clinical deterioration and/or bailout (5.0% vs 5.7%, p=0.77). RV/LV ratio reduction (19.9% vs 23.1%, p=0.10) and respirations per minute (20.0 vs 19.9, p=0.62) were not statistically different at the 24-hour visit. PEmb-QoL (18.5 vs 23.0, p=0.18) and EQ-5D-5L (0.84 vs 0.81, p=0.85) were also not different at the 30-day visit. Conclusion Treatment duration and tPA dose were significantly lower in patients treated with USAT; however, clinical outcomes did not differ significantly between USAT and SCDT. This suggests that the primary analysis of [REDACTED] may be generalizable to tPA-based CDT treatment protocols currently in use.

Topic: Venous Thromboembolism Diagnosis and Management
Subfield: Internal Medicine
Field: Medicine
Domain: Health Sciences
A Concise Route for the Synthesis of Tetracyclic Meroterpenoids: (±)-Aureol Preparation and Mechanistic Interpretation

A new concise general methodology for the synthesis of different tetracyclic meroterpenoids is reported: (±)-aureol (1), the key intermediate of this general route. The synthesis of (±)-aureol (1) was achieved in seven steps (28% overall yield) from (±)-albicanol. The key steps of this route include a C–C bond-forming reaction between (±)-albicanal and a lithiated arene unit and a rearrangement involving 1,2-hydride and 1,2-methyl shifts promoted by BF3•Et2O as activator and water as initiator.

Topic: Synthetic Organic Chemistry Methods
Subfield: Organic Chemistry
Field: Chemistry
Domain: Physical Sciences
Non-nutritive sucking habits in children- A review of deterimental effects on oral facial complex

The detrimental effects of prolonged non-nutritive sucking habits in children on the developing oral structures are often the primary focus of dental professionals. The development and maturation of normal oropharyngeal function plays an important role in craniofacial growth and occlusal physiology. Any muscular imbalance caused by intrinsic or extrinsic pressure will show their effect on the growing bone which will result in malocclusion. One of the important factors resulting in malocclusion is oral habit practiced by a child. However, non-nutritive sucking with a pacifier has other consequences that include not only harmful effect but positive influences as well. Public health policies should be adopted to encourage a longer duration of breastfeeding, thereby contributing towards reducing the prevalence of non-nutritive sucking habits and anterior open bite.

Topic: Cleft Lip and Palate Research
Subfield: Genetics
Field: Biochemistry, Genetics and Molecular Biology
Domain: Life Sciences
The activity <i>in vitro</i> against herpes virus of 9-(2-hydroxyethoxymethyl)guanine (acycloguanosine), a new antiviral agent

The antiviral activity of acycloguanosine in vitro was compared with that of idoxuridine, cytarabine, trifluorothymidine, vidarabine and phosphonoacetic acid by means of plaque reduction assays in VERO cells with several strains of type 1 and type 2 herpes virus. The dose-response lines thus obtained showed that acycloguanosine was considerably more active than the other compounds. The activity of all compounds was somewhat lower in HeLa cells. Acycloguanosine was equally effective against type 1 and type 2 herpes, and individual strains varied little in their sensitivity. The other compounds showed wider variations in strain sensitivity, with a tendency for type 2 strains to be less sensitive. Preliminary studies with acycloguanosine showed that its antiviral action took place in the early stages of the multiplication cycle of the virus. Acycloguanosine had very low toxicity to VERO cells. At concentrations at the limit of solubility (20,000 μM), it caused only limited changes in cell morphology and inhibition of cell growth which was reversible. The favourable properties of acycloguanosine indicate that it may be of clinical use in the treatment of herpes virus infections.

Topic: Herpesvirus Infections and Treatments
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Outcome in Stroke Patients Is Associated with Age and Fractional Anisotropy in the Cerebral Peduncles: A Multivariate Regression Study

Neural damage in the corticospinal tracts (indicated by rFA) had the strongest effect on outcome measures, whereas the level of disability (measured by FIM-motor) was associated with a broader range of factors, including age.

Topic: Advanced Neuroimaging Techniques and Applications
Subfield: Radiology, Nuclear Medicine and Imaging
Field: Medicine
Domain: Health Sciences
PRISM: Patient Records Interpretation for Semantic Clinical Trial Matching using Large Language Models

Clinical trial matching is the task of identifying trials for which patients may be potentially eligible. Typically, this task is labor-intensive and requires detailed verification of patient electronic health records (EHRs) against the stringent inclusion and exclusion criteria of clinical trials. This process is manual, time-intensive, and challenging to scale up, resulting in many patients missing out on potential therapeutic options. Recent advancements in Large Language Models (LLMs) have made automating patient-trial matching possible, as shown in multiple concurrent research studies. However, the current approaches are confined to constrained, often synthetic datasets that do not adequately mirror the complexities encountered in real-world medical data. In this study, we present the first, end-to-end large-scale empirical evaluation of clinical trial matching using real-world EHRs. Our study showcases the capability of LLMs to accurately match patients with appropriate clinical trials. We perform experiments with proprietary LLMs, including GPT-4 and GPT-3.5, as well as our custom fine-tuned model called OncoLLM and show that OncoLLM, despite its significantly smaller size, not only outperforms GPT-3.5 but also matches the performance of qualified medical doctors. All experiments were carried out on real-world EHRs that include clinical notes and available clinical trials from a single cancer center in the United States.

Topic: Biomedical Text Mining and Ontologies
Subfield: Molecular Biology
Field: Biochemistry, Genetics and Molecular Biology
Domain: Life Sciences
TRANSFER-OF-TRAINING EFFECTS IN PROCESSING INSTRUCTION

This study compares the effects of processing instruction (PI), structured input (SI), and form-related explicit information (FREI) on a primary target form (i.e., third-person Spanish accusative clitics) and on a secondary form (i.e., third-person Spanish dative clitics). Participants included 151 adult learners enrolled in a beginning-level Spanish course. Findings revealed that SI is as effective on the primary target form as PI immediately after treatment; however, the FREI component of PI may play a positive role at the delayed posttest, as exhibited by the fact that the PI group maintained gains, whereas the SI group, although improved from the pretest, did not. Learners exposed to both PI and SI also demonstrated gains on the secondary target form, which suggests a transfer-of-training effect for both interventions. As such, we discuss the theoretical and methodological ramifications of these findings.

Topic: EFL/ESL Teaching and Learning
Subfield: Language and Linguistics
Field: Arts and Humanities
Domain: Social Sciences
Effects of Aqueous Extract of Phyllanthus muellerianus Leaves on Castor Oil-induced Diarrhoeal Rats

Effects of Aqueous Extract of Phyllanthus muellerianus Leaves on Castor Oil-induced Diarrhoeal Rats Cancer is one of the leading causes of death and globally the numbers of cases of cancer are increasing gradually. There are several medicines available in the market to treat the various types of cancer but no drug is found to be fully effective and safe. The major problem in the cancer chemotherapy is the toxicity of the established drugs. However plants and plant derived products have proved effective and safe in the treatment and management of cancers. These days most of the research work on cancer drugs is targeted on plants and plants derived natural products. Many natural products and their analogues have been identified as potent anti-cancer agents and day by day the anti-cancer property of various plants is being identified. Here an attempt is being made through this review to highlights the natural products and their analogues established as anti-cancer agents and the new plant species identified with anti-cancer properties either in vivo or in vitro.Aqueous extract of Phyllanthus muellerianus (Phyllanthaceae) leaves was screened for its constituents. Antidarrhoeal property of the extract at the doses of 12.50, 25 and 50 mg/kg body weight was also evaluated using models, such as castor oil-induced diarrhoeal, intestinal transit and enteropooling. Phytochemical screening revealed the presence of cardenolides (0.33%), cardiac glycosides (0.51%), flavonoids (0.16%), saponins (1.21%), tannins (0.68%) and triterpenes (0.08%), while alkaloids, anthaquinones, phlobatannins and steroids were not detected.

Topic: Phytochemistry and Bioactivity Studies
Subfield: Pharmacology
Field: Pharmacology, Toxicology and Pharmaceutics
Domain: Life Sciences
ON THE VERY HIGH ENERGY PULSED EMISSION IN THE CRAB PULSAR

We have examined the recently detected very high energy (VHE) pulsed\nradiation from the Crab pulsar. According to the observational evidence, the\nobserved emission (&gt;25GeV) peaks at the same phase with the optical spectrum.\nConsidering the cyclotron instability, we show that the pitch angle becomes\nnon-vanishing leading to the efficient synchrotron mechanism near the light\ncylinder surface. The corresponding spectral index of the emission equals -1/2.\nBy studying the inverse Compton scattering and the curvature radiation, it is\nargued that the aforementioned mechanisms do not contribute to the VHE\nradiation detected by MAGIC.\n

Topic: Pulsars and Gravitational Waves Research
Subfield: Astronomy and Astrophysics
Field: Physics and Astronomy
Domain: Physical Sciences
A survey of cellular slime molds at selected sites on the James River, Virginia

Forty-three sample sites representing seven plant associations were surveyed for cellular slime molds in the James River basin from the head-waters to the mouth of the James River. Dictyostelium rnucoroides, D. minutum, D. purpureum, Q· discoideum, Polysphondylium violaceum and ~· pallidum were found in all associations. Dictyostelium lacteum was found in all but the MapleBasswood association. The remaining species were unique to the Alluvial Hardwood association and the following respective forest types: D. polycephalum to Oak-Hickory, Q· giganteurn to Oak-Hickory and Mixed Mesophytic, and D. rosarium to Mixed Mesophytic. A percentage similarity test indicated that, with regards to the observed dictyostelid flora, sample sites were most similar to those within the same plant association. A SURVEY OF CELLULAR SLIME MOLDS AT SELECTED SITES ON THE JAMES RIVER, VIRGINIA by Nathaniel LeMaster Armistead III

Topic: Slime Mold and Myxomycetes Research
Subfield: Biomedical Engineering
Field: Engineering
Domain: Physical Sciences
New genotypes of the species Thymus x citriodorus (pers.) Schreb. – production and quality

The article presents the results of CCC testing of a new cultivar of lemon thyme – Citro-nel-pink of the species Thymus x citriodorus (Pers.) Schreb. as pharmaceutical remedy, food and melliferous plant, obtained by clonal selection, for the purpose of promoting and imple-menting it in industrial production.

Topic: Plant tissue culture and regeneration
Subfield: Molecular Biology
Field: Biochemistry, Genetics and Molecular Biology
Domain: Life Sciences
Extracellular enzyme activity of entomopathogenic fungi, Beauveria bassiana and Metarhizium anisopliae and their pathogenicity potential as a bio-control agent against whitefly pests, Bemisia tabaci and Trialeurodes vaporariorum (Hemiptera: Aleyrodidae)

Abstract Objective This study was aimed to assess the enzymatic activity and pathogenicity potential of Beauveria bassiana and Metarhizium anisopliae against whiteflies in Ethiopia. Results The data showed that Beauveria bassiana AAUMB-29, AAUMFB-77, and AAUEB-59 generated the highest chitinase (EI = 3.41), lipase (EI = 4.45), and protease activities (EI = 5.44) respectively. The pathogenicity study of isolates on whitefly nymphs and adults indicated significant variation (P < 0.05) with mortality ranging from 71.67 to 98.33% and 60 to 100% against Bemisia tabaci and Trialeurodes vaporariorum nymphs respectively. The mortality of adults was between 58 and 94.27% against B. tabaci and 59.03 to 95.37% against T.vaporariorum. The result also showed that AAUMB-29, AAUMFB-77, and AAUDM-43 were the most virulent with LC 50 values of 2.7 × 10 4 , 5.3 × 10 4 , and 5.4 × 10 4 conidia/ml against nymphs of B. tabaci , and with LC 50 values 6.8 × 10 4 , 8.2 × 10 4 , and 7.2 × 10 4 conidia/ml against nymphs of T. vaporariorum , respectively. The B. bassiana AAUMB-29, B. bassiana AAUMFB-77, and M. anisopliae AAUDM-43 induced the highest whitefly mortality than other isolates. These isolates can be recommended for further tests under field conditions to fully realize their potential as effective biocontrol agents against whitefly pests in tomato.

Topic: Entomopathogenic Microorganisms in Pest Control
Subfield: Insect Science
Field: Agricultural and Biological Sciences
Domain: Life Sciences
Reduced Argatroban Doses After Coronary Artery Bypass Graft Surgery

Background: The Food and Drug Administration–approved argatroban dose for heparin-induced thrombocytopenia (HIT) is 2 μg/kg/min (0.5 μg/kg/min in hepatic impairment), adjusted to achieve activated partial thromboplastin time (aPTT) 1.5–3 times baseline. Recent data suggest that reduced doses are required after cardiovascular surgery. Objective: To characterize dosing requirements, aPTTs, factors affecting dosage, and clinical outcomes in patients administered argatroban after coronary artery bypass graft (CABG) surgery. Methods: Charts of 39 patients who underwent CABG surgery and were administered argatroban postoperatively for laboratory-confirmed HIT (n = 25), antibody-negative suspected HIT (n = 10), or previous HIT requiring anticoagulation (n = 4) were retrospectively reviewed. Patient characteristics, argatroban dosing information, aPTTs (target range 45–90 sec), and outcomes were summarized. Regression analyses explored potential effectors of dosage. Results: Patient features, argatroban dosing patterns, and aPTTs were similar among groups. Many patients had laboratory evidence of some hepatic and/or renal dysfunction (median [range] bilirubin 1.0 [0.3–8.0] mg/dL, creatinine clearance 47 [18–287] mL/min). Overall, median argatroban doses were 0.5 μg/kg/min initially and 0.6 μg/kg/min during therapy (median duration 5.3 days). After argatroban initiation, aPTTs were greater than 90 seconds at first assessment in 4 patients (3 with abnormal hepatic function test results) initially administered 0.5, 1, 2, and 2 μg/kg/min, respectively. Within approximately 16 hours of therapy, 33 (85%) patients achieved consecutive therapeutic aPTTs. No association was detected between mean dose during therapy and preoperative ejection fraction, routine hepatic or renal function test results (other than blood urea nitrogen [BUN]), or surgery type. A clinically insignificant association existed between dose and BUN: there was an approximately 0.15 μg/kg/min dose decrease for each 10 mg/dL BUN increase. One patient developed thrombosis, 1 underwent finger amputation, 7 died (5 after argatroban cessation), and 4 had significant bleeding. Conclusions: These findings suggest that reduced initial argatroban doses (eg, 0.5 μg/kg/min), adjusted to achieve therapeutic aPTTs, provide rapid, adequate anticoagulation in postoperative CABG patients with presumed or previous HIT. Prospective study of reduced initial dosing in this setting is warranted.

Topic: Heparin-Induced Thrombocytopenia and Thrombosis
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Construction of a Nomogram to Predict the Progression Free Survival in Patients With Lung Cancer

<title>Abstract</title> <bold>PURPOSE</bold> For a personalized cancer prognosis, a nomogram is a practical and helpful tool. In addition to creating a clinical nomogram to forecast progression free survival (PFS) for patients with various histological types, clinical stages, and treatment regimens, our goals included assessing the prognostic variables of lung cancer (LC) patients. <bold>METHODS</bold> Clinical characteristics, peripheral blood parameters, and treatment records were collected from 1200 newly diagnosed LC patients in the Medical Oncology Department at Mohammed VI University Hospital in Marrakech between 2013 and 2021. Cox Proportional Hazards Regression Analysis was used to identify the independent prognostic factors. The nomogram we created and tested was used to predict the PFS of patients with LC. The Kaplan-Meier survival curves were drawn, stratified, and compared using the log rank test. <bold>RESULTS</bold> A total of 342 individuals met the inclusion criteria and were then included in the study. Prognostic factors for LC included gender, tabacco status, number of cures of the first-line chemotherapy, radiotherapy, and thrombocytopenia; these factors were combined to create the nomogram. The clinical prediction model performed satisfactorily in prognosis prediction, as evidenced by the calibration and receiver operating characteristics curves. In comparison to the clinical TNM staging method for a one-year prediction, the nomogram's area under the ROC curve (AUC) value for 6- and 12-month PFS rates was 0.8 and 0.83, respectively. <bold>CONCLUSION</bold> We developed and verified a unique nomogram that can offer personalised PFS predictions for Moroccan and African LC patients. The development of this tool is extremely important for clinical study design and decision-making.

Topic: Lung Cancer Diagnosis and Treatment
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Ruck Frequency as a predictor of success in the 2007 Rugby World Cup Tournament

An evaluation of the 2007 Rugby World Cup was conducted to establish if ruck occurrence could predict successful performance. These data were compared with the 6 Nations and Tri Nations competitions of 2007. There were 117 (range 65 – 172) rucks per match. The knockout stages had a greater number of rucks per game (121 range 71-164) than the pool stages (116 range 65-172). 66% of rucks occurred in the midfield zones, 28% in the attacking and 7% in the defensive zones. Comparisons with the 6 Nations and Tri Nations revealed that there were 20% fewer rucks during World Cup matches. Matches during the pool stages were won (58%) by teams with the highest number of rucks. This was also observed during the 6 Nations and the Tri Nations. In the knockout stages the team with the fewest rucks won 100% of the matches. These data suggest that during International rugby competitions and pool stages of a World Cup, the greater the number of rucks that a team creates, the more likely it is to win the match. This strategy was not effective during the knockout stages of the Rugby World Cup; here the avoidance of rucking was associated with success.

Topic: Sports Performance and Training
Subfield: Orthopedics and Sports Medicine
Field: Medicine
Domain: Health Sciences