Miracle-dz/UniFAR-FTUs huggingface dataset:
Design and Hybridization Properties of Acyclic Xeno Nucleic Acid Oligomers

Xeno nucleic acids (XNAs) are analogues of DNA and RNA that have a non‐ribose artificial scaffold. XNAs are possible prebiotic genetic carriers as well as alternative genetic systems in artificial life. In addition, XNA oligomers can be used as biological tools. Acyclic XNAs, which do not have cyclic scaffolds, are attractive due to facile their synthesis and remarkably high nuclease resistance. To maximize the performance of XNAs, a negatively charged backbone is preferable to provide sufficient water solubility; however, acyclic XNAs containing polyanionic backbones suffer from high entropy cost upon duplex formation, because of the high flexibility of the acyclic nature. Herein, we review the relationships between the structure and duplex hybridization properties of various acyclic XNA oligomers with polyanion backbones.
Healthy Food Prescription Programs and their Impact on Dietary Behavior and Cardiometabolic Risk Factors: A Systematic Review and Meta-Analysis.

The enormous burden of diet-related chronic diseases has prompted interest in healthy food prescription programs. Yet, the impact of such programs remains unclear. The aim of this study was to conduct a systematic review of healthy food prescription programs and evaluate their impact on dietary behavior and cardiometabolic parameters by meta-analysis. A systematic search was carried out in Medline, Embase, Scopus, and Cochrane Central Register of Controlled Trials databases since their inception to 3 January, 2020 without language restriction. A systematic search of interventional studies investigating the effect of healthy food prescription on diet quality and/or cardiometabolic risk factors including BMI, systolic (SBP) and diastolic blood pressure (DBP), glycated hemoglobin (HbA1c), or blood lipids was carried out. Thirteen studies were identified for inclusion, most of which were quasi-experimental (pre/post) interventions without a control group (n = 9). Pooled estimates revealed a 22% (95% CI: 12, 32; n = 5 studies, n = 1039 participants; I2 = 97%) increase in fruit and vegetable consumption, corresponding to 0.8 higher daily servings (95% CI: 0.2, 1.4; I2 = 96%). BMI decreased by 0.6 kg/m2 (95% CI: 0.2, 1.1; I2 = 6.4%) and HbA1c by 0.8% (95% CI: 0.1, 1.6; I2 = 92%). No significant change was observed in other cardiometabolic parameters. These findings should be interpreted with caution in light of considerable heterogeneity, methodological limitations of the included studies, and moderate to very low certainty of evidence. Our results support the need for well-designed, large, randomized controlled trials in various settings to further establish the efficacy of healthy food prescription programs on diet quality and cardiometabolic health.
Simulation Training Improves Trainee Technical Skill and Procedural Attitudes in Endoscopic Gastrostomy Tube Placement

Introduction Percutaneous endoscopic gastrostomy (PEG) tube placement remains a core competency of gastroenterology fellowship, although this procedure is performed infrequently. Some training programs lack sufficient procedural volume for trainees to develop confidence and competence in this procedure. We aimed to determine the impact of a simulation-based educational intervention on trainee technical skill and procedural attitudes in simulated PEG tube placement. Methods Gastroenterology fellows were invited to participate in the study. Baseline procedural attitudes toward PEG tube placement (self-confidence, perceived skill level, perceived level of required supervision) were assessed before simulation training using a Likert scale. Baseline technical skills were assessed by video recording–simulated PEG tube placement on a PEG tube simulator with scoring using a procedural checklist. Fellows next underwent individualized simulation training and repeated simulated PEG tube placement until greater than 90% of checklist items were achieved. Procedural attitudes were reassessed directly after the simulation. Technical skill and procedural attitudes were then reassessed 6 to 12 weeks later (delayed posttraining). Results Twelve fellows completed the study. Simulation training led to significant improvement in technical skill at delayed reassessment (52.9 ± 14.3% vs. 78.0 ± 8.9% correct, P = 0.0002). Simulation training also led to significant immediate improvements in self-confidence (2.1 ± 0.7 vs. 3.1 ± 0.3, P = 0.001), perceived skill level (2.2 ± 1.0 vs. 4 ± 1.1, P < 0.001), and perceived level of required supervision (2.2 ± 0.9 vs. 3.2 ± 0.6, P = 0.003). Conclusions Simulation training led to sustained improvements in gastroenterology fellows' technical skill and procedural attitudes in PEG tube placement. Incorporation of simulation curricula in gastroenterology fellowships for this infrequently performed procedure should be considered.
Hinge like domain motion facilitates human RBMS1 protein binding to proto-oncogene c-myc promoter

Abstract DNA binding proteins recognize DNA specifically or non-specifically using direct and indirect readout mechanisms like sliding, hopping, and diffusion. However, a common difficulty in explicitly elucidating any particular mechanism of site-specific DNA-protein recognition is the lack of knowledge regarding target sequences and inadequate account of non-specific interactions, in general. Here, we decipher the structural basis of target search performed by the key regulator of expression of c-myc proto-oncogene, the human RBMS1 protein. In this study, we have shown the structural reorganization of this multi-domain protein required for recognizing the specific c-myc promoter sequence. The results suggest that a synergy between structural re-organization and thermodynamics is necessary for the recognition of target sequences. The study presents another perspective of looking at the DNA-protein interactions.
A study on dissociation of sII krypton hydrate and the effect of hydrocarbon guest molecules as stabilizer by molecular dynamics simulation

ABSTRACT In this paper, the characteristics of structure II krypton hydrate are studied by molecular dynamics simulation under isobaric-isothermal (NPT) ensemble condition. The dissociation process of the hydrate is simulated and the effect of krypton (Kr) and various types of hydrocarbon guest molecules (HGMs) on the stability of the hydrate structure is investigated during the simulation time of 1 ns. The studied HGMs are propane, isobutane, neopentane, cyclopropane, cyclobutane, cyclopentane and cyclopentene. The structural change of the Kr-hydrate is analyzed with the radial distribution function, mean square displacement and diffusion coefficient. As temperature increases, the obtained results indicate a gradual increase in the Kr-hydrate cell size, which leads to distortion of the hydrate lattice and escaping of the encapsulated Kr molecules from the hydrate structure to form small bubbles of Kr aggregated in the aqueous solution.
The environmental context of inducible HSP70 expression in Eastern Brook Trout.

Much research has focused on the population-level effects of climate change on Eastern Brook Trout (Salvelinus fontinalis). While some studies have considered here sub-lethal stress caused by warming waters, the role of multiple, interacting stressors remains largely unexplored. We used inducible heat shock protein 70 (HSP70) as a molecular biomarker to assess in situ response of Eastern Brook Trout in headwater streams to multiple potential stressors, including temperature. Over 7 sampling events during 2018 and 2019, we sampled 141 fish and found that HSP70 expression and 3-day mean water temperature exhibited a quadratic relationship (R 2-adj = 0.68). Further analyses showed that HSP70 expression was explained by temperature, relative water level and their interaction (R 2-adj = 0.75), while fish size and capture location were not factors. We observed a significant increase in HSP70 expression during periods of low relative water level with warm temperatures (~18°C) and also during high relative water level with cold temperatures (~8°C). Our results suggest that temperatures at the edges of the preferred range coupled with relative water level might act together to trigger the cellular stress response in Eastern Brook Trout and that there is greater variation in response at colder temperatures. These findings reinforce the need to consider complex, interactive stressors in influencing the health and persistence of Eastern Brook Trout populations into the future.
Preoperative Inflammatory Markers as a Predictor of Three-Year Overall Survival in Older Cancer Patients Undergoing Oncologic Surgery

Simple Summary Older patients can have an increased expression of inflammatory cytokines due to ageing of the immune system. It is likely that older cancer patients with a low-grade inflammatory state are more at risk for an exaggerated inflammatory response to surgery and for poor outcome after surgery. The aim of this study was to examine whether preoperative inflammatory markers could be a predictor of overall survival in older patients undergoing oncologic surgery. In this prospective cohort study, a plasma level of C-reactive protein (CRP) ≥ 10 mg/L was a predictor of inferior three-year overall survival after oncologic surgery in older cancer patients, and also for the specific group of older patients with a colorectal tumor. Measuring preoperative plasma level of CRP might be useful in risk stratification for poor outcome after surgery in older cancer patients. Abstract Oncologic surgery results in substantially higher morbidity and mortality rates in older patients compared to younger patients, yet little is known about the relation between the preoperative inflammatory state and postoperative outcome in the specific group of older cancer patients. The aim of this study was to examine whether preoperative inflammatory markers could be a predictor of overall survival in older patients undergoing elective surgery for a solid malignant tumor. Patients 65 years and older undergoing surgery for a solid malignant tumor were included in a prospective cohort study. Inflammatory markers C-reactive protein (CRP), interleukin-1 beta (IL-1β), IL-6, IL10, IL-12 and tumor necrosis factor-alpha (TNF-α) were measured in plasma samples preoperatively. The main outcome was overall survival three years after surgery. Between 2010 and 2016, 328 patients with a median age of 71.5 years (range 65–89) were included. A significantly higher mortality rate three years after surgery, was found in patients with high preoperative plasma levels of CRP and IL-6 (p = 0.013 and p = 0.046, respectively). In multivariate analysis, corrected for variables such as age, disease stage, frailty, comorbidities, type of surgery and complications, a preoperative plasma level of CRP ≥ 10 mg/L was an independent prognostic factor for inferior overall survival three years after surgery (multivariate hazard ratio 1.50, 95% confidence interval 1.04–2.16, p = 0.031). Also, for the specific group of patients with colorectal cancer, a preoperative plasma level of CRP ≥ 10 mg/L was a prognostic factor for inferior survival three years after surgery (multivariate hazard ratio 2.40, 95% confidence interval 1.20–4.81, p = 0.014). Preoperative elevated plasma level of CRP is an independent unfavorable prognostic factor for overall survival three years after oncologic surgery. This gives more insight into the relationship between inflammation and survival in older cancer patients, and might contribute to risk stratification for poor outcome after surgery in older cancer patients.
A multidisciplinary team approach to screening, assessment and early intervention for young people with type 1 diabetes and disordered eating behaviour

Introduction: Recent NICE guidelines have emphasised the need for diabetes and eating disorder teams to collaborate in order to provide safe and effective treatment for young people with type 1 diabetes and eating disorders. Aim: Our aim was to examine and describe the current treatment journeys for young people under the care of our paediatric diabetes team who presented with eating difficulties and body image concerns. We also sought to increase staff awareness, communication and opportunities for joint working across the diabetes and eating disorders teams. Method: Information regarding the screening, assessment and interventions offered to young people with type 1 diabetes and eating difficulties was collected. A joint training event was developed and attended by healthcare professionals from the diabetes and eating disorder teams. Results: Information collected regarding patient’s treatment journeys was used to inform the multidisciplinary pathway. The joint training event offered the opportunity for shared learning, and identification of areas for service improvement.
New quinoxalin‐1,3,4‐oxadiazole derivatives: Synthesis, characterization, in vitro biological evaluations, and molecular modeling studies

A new series of quinoxalin‐1,3,4‐oxadiazole (10a–l) derivatives was synthesized and evaluated against some metabolic enzymes including human carbonic anhydrase (hCA) isoenzymes I and II (carbonic anhydrases I and II), cholinesterase (acetylcholinesterase and butyrylcholinesterase), and α‐glucosidase. Obtained data revealed that all the synthesized compounds were more potent as compared with the used standard inhibitors against studied target enzymes. Among the synthesized compounds, 4‐fluoro derivative (10f) against hCA I, 4‐chloro derivative (10i) against hCA II, 3‐fluoro derivative (10e) against acetylcholinesterase and butyrylcholinesterase, and 3‐bromo derivative (10k) against α‐glucosidase were the most potent compounds with inhibitory activity around 1.8‐ to 7.37‐fold better than standard inhibitors. Furthermore, docking studies of these compounds were performed at the active site of their target enzymes.
Prognostic implications of left ventricular myocardial work index in patients with ST-segment elevation myocardial infarction and reduced left ventricular ejection fraction.

AIMS This study aimed to determine whether lower values of left ventricular (LV) global work index (GWI) at baseline were associated with a reduction in LV functional recovery and poorer long-term prognosis in patients with reduced LV ejection fraction (LVEF ≤40%) following ST-segment elevation myocardial infarction (STEMI). METHODS AND RESULTS A total of 197 individuals (62 ± 12 years, 75% male) with STEMI treated with primary percutaneous coronary intervention and reduced LVEF were evaluated. All patients were followed up for the occurrence of all-cause mortality and the presence of LVEF normalization at 6 months (LVEF ≥50%). The median LVEF was 36% (interquartile range 32-38) and the mean value of LV GWI was 1041 ± 404 mmHg% at baseline. At 6-month follow-up, 41% of patients had normalized LVEF. On multivariable logistic regression, higher values of LV GWI were independently associated with LVEF normalization at 6 months of follow-up (odds ratio 1.32 per 250 mmHg%, P = 0.038). Over a median follow-up of 112 months, 40 patients (20%) died. LV GWI <750 mmHg% was independently associated with all-cause mortality (HR 3.85, P < 0.001) and was incremental to LV global longitudinal strain (P = 0.039) and LVEF (P < 0.001). CONCLUSION In individuals with an LVEF ≤40% following STEMI, higher values of LV GWI were associated with a greater probability of LVEF normalization at 6-month follow-up. In addition, lower values of LV GWI were independently associated with increased all-cause mortality at long-term follow-up, providing incremental prognostic value over LVEF and minor incremental prognostic value over LV global longitudinal strain.
uPA‐PAI‐1 heteromerization promotes breast cancer progression by attracting tumorigenic neutrophils

High intratumoral levels of urokinase‐type plasminogen activator (uPA)‐plasminogen activator inhibitor‐1 (PAI‐1) heteromers predict impaired survival and treatment response in early breast cancer. The pathogenetic role of this protein complex remains obscure. Here, we demonstrate that heteromerization of uPA and PAI‐1 multiplies the potential of the single proteins to attract pro‐tumorigenic neutrophils. To this end, tumor‐released uPA‐PAI‐1 utilizes very low‐density lipoprotein receptor and mitogen‐activated protein kinases to initiate a pro‐inflammatory program in perivascular macrophages. This enforces neutrophil trafficking to cancerous lesions and skews these immune cells toward a pro‐tumorigenic phenotype, thus supporting tumor growth and metastasis. Blockade of uPA‐PAI‐1 heteromerization by a novel small‐molecule inhibitor interfered with these events and effectively prevented tumor progression. Our findings identify a therapeutically targetable, hitherto unknown interplay between hemostasis and innate immunity that drives breast cancer progression. As a personalized immunotherapeutic strategy, blockade of uPA‐PAI‐1 heteromerization might be particularly beneficial for patients with highly aggressive uPA‐PAI‐1high tumors.
ASPRE trial: risk factors for development of preterm pre‐eclampsia despite aspirin prophylaxis

To examine the possible risk factors amongst maternal characteristics, medical and obstetric history, pre‐eclampsia (PE)‐specific biomarkers and estimated‐risk group, according to The Fetal Medicine Foundation (FMF) algorithm, that are associated with the development of preterm PE with delivery at < 37 weeks' gestation despite aspirin prophylaxis.
Shark tooth collagen stable isotopes (δ15 N and δ13 C) as ecological proxies.

The isotopic composition of tooth-bound collagen has long been used to reconstruct dietary patterns of animals in extant and paleoecological systems. For sharks that replace teeth rapidly in a conveyor-like system, stable isotopes of tooth collagen (δ13 Ctooth & δ15 Ntooth ) are poorly understood and lacking in ecological context relative to other non-lethally sampled tissues. This tissue holds promise, because shark jaws may preserve isotopic chronologies from which to infer individual-level ecological patterns across a range of temporal resolutions. Carbon and nitrogen stable isotope values were measured and compared between extracted tooth collagen and four other, non-lethally sampled tissues of varying isotopic turnover rates: blood plasma, red blood cells, fin, and muscle, from eight species of sharks. Individual-level isotopic variability of shark tooth collagen was evaluated by profiling teeth of different ages across whole jaws for the shortfin mako shark Isurus oxyrinchus and sandbar shark Carcharhinus plumbeus. Measurements of δ13 Ctooth and δ15 Ntooth were positively correlated with isotopic values from the four other tissues. Collagen δ13 C was consistently 13 C-enriched relative to all other tissues. Patterns for δ15 N were slightly less uniform; tooth collagen was generally 15 N-enriched relative to muscle and red blood cells, but congruent with fin and blood plasma (values clustered around a 1:1 relationship). Significant within-individual isotopic variability was observed across whole shortfin mako shark (δ13 C range = 3.5‰, δ15 N range = 3.8‰) and sandbar shark (δ13 C range = 2.4‰ -5.4‰, δ15 N range = 2.4‰ - 5.8‰) jaws, which trended with tooth age. We conclude that tissue amino acid composition and associated patterns of isotopic fractionation result in predictable isotopic offsets between tissues. Future measurements will refine the use of this tissue as an ecological and paleoecological proxy. Within-individual variability of tooth stable isotope values suggests teeth of different ages may serve as ecological chronologies, which could be applied to studies on migration and individual-level diet variation across diverse time scales. Improvements in understanding tooth replacement rates, isotopic turnover, and associated fractionation of tooth collagen will enhance inferences that can be made from the isotopic composition of shark tooth, outlining clear goals for future scientific inquiry.
The Development of a Digital Patient-Reported Outcome Measurement for Adults With Chronic Disease (The Parsley Symptom Index): Prospective Cohort Study

Background The monitoring and management of chronic illness has always been a challenge. Patient-reported outcome measures (PROMs) can be powerful tools for monitoring symptoms and guiding treatment of chronic diseases, but the available PROM tools are either too broad or too disease specific for the needs of a primary care practice focused on longitudinal care. Objective In this study we describe the development and preliminary validation of the Parsley Symptom Index (PSI). Methods This prospective cohort study took place from January 5, 2018, to June 05, 2020, among a sample of 4621 adult patients at Parsley Health. After a review of literature, followed by binning and winnowing of potential items, a 45-item PROM that also served as a review of systems (ROS) was developed. The PSI was deployed and completed by patients via an online portal. Construct and face validity was performed by clinicians, tested on patients, and feasibility was measured by response rate, completion rate, and percentage of missing data. Results The response rate for 12,175 collected PSIs was 93.72% (4331/4621) with a 100% item completion rate. A confirmatory factor analysis confirmed the model structure was satisfactory by a Comparative Fit Index of 0.943, Tucker–Lewis index of 0.938, and root mean square error of approximation of 0.028. Conclusions A 45-item ROS-style PROM designed to capture chronic disease symptoms was developed, and preliminary validation suggests that the PSI can be deployed, completed, and helpful to both patients and clinicians.
Contemporary National Patterns of Eligibility and Use of Novel Cardioprotective Antihyperglycemic Agents in Type 2 Diabetes Mellitus

Background SGLT‐2 (sodium glucose transporter‐2) inhibitors and GLP‐1RAs (glucagon‐like peptide‐1 receptor agonists) effectively lowered cardiovascular risk in large clinical trials for patients with type 2 diabetes mellitus at high risk for these complications, and have been recommended by guidelines. To evaluate the contemporary landscape in which these recommendations would be implemented, we examined the use of these medications according to clinical guideline practice. Methods and Results In the National Health and Nutrition Examination Survey for 2017 to 2018, we defined compelling indications for SGLT‐2 inhibitors by the presence of atherosclerotic cardiovascular disease, heart failure, or chronic kidney disease, and for GLP‐1RAs by the presence of established or high‐risk atherosclerotic cardiovascular disease, based on large clinical trials that have been incorporated in guideline recommendations of the American College of Cardiology and American Diabetes Association. We then evaluated use of these medications among patients with physician‐diagnosed type 2 diabetes mellitus. All analyses incorporated complex survey design to produce nationally representative estimates. A total 1104 of 9254 sampled individuals had type 2 diabetes mellitus, representing 10.6% (95% CI, 9.7%–11.6%) of the US population or 33.2 million adults nationally. Of these, 52.6% (95% CI, 47.7%–57.5%) had an indication for SGLT‐2 inhibitors, 32.8% (95% CI, 28.8%–37.2%) for GLP‐1RAs, and 26.6% (95% CI, 22.2%–31.7%) for both medications. During 2017 to 2018, 4.5% (95% CI, 2.4%–8.2%) were treated with SGLT‐2 inhibitors and 1.5% (95% CI, 0.7%–3.2%) with GLP‐1RAs. Atherosclerotic cardiovascular disease, heart failure, or chronic kidney disease were not independently associated with SGLT‐2 inhibitor or GLP‐1RA use in patients with diabetes mellitus. Conclusions Despite a large number of patients being eligible for guideline‐recommended cardiorenal protective therapies, there are substantial gaps in the use of SGLT‐2 inhibitors and GLP‐1RAs, limiting their public health benefits.