16 results on '"Shepherd ST"'
Search Results
2. Protein-ligand binding affinity prediction based on profiles of intermolecular contacts.
- Author
-
Wang DD and Chan MT
- Abstract
As a key element in structure-based drug design, binding affinity prediction (BAP) for putative protein-ligand complexes can be efficiently achieved by the incorporation of structural descriptors and machine-learning models. However, developing concise descriptors that will lead to accurate and interpretable BAP remains a difficult problem in this field. Herein, we introduce the profiles of intermolecular contacts (IMCPs) as descriptors for machine-learning-based BAP. IMCPs describe each group of protein-ligand contacts by the count and average distance of the group members, and collaborate closely with classical machine-learning models. Performed on multiple validation sets, IMCP-based models often result in better BAP accuracy than those originating from other similar descriptors. Additionally, IMCPs are simple and concise, and easy to interpret in model training. These descriptors highly conclude the structural information of protein-ligand complexes and can be easily updated with personalized profile features. IMCPs have been implemented in the BAP Toolkit on github ( https://github.com/debbydanwang/BAP)., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Author(s).)
- Published
- 2022
- Full Text
- View/download PDF
3. Association of timing of congenital diaphragmatic hernia repair with survival and morbidity for patients not requiring extra-corporeal life support.
- Author
-
Gupta VS, Shepherd ST, Ebanks AH, Lally KP, Harting MT, and Basir MA
- Subjects
- Infant, Humans, Herniorrhaphy, Morbidity, Retrospective Studies, Hernias, Diaphragmatic, Congenital surgery
- Abstract
Background: While physiologic stabilization followed by repair has become the accepted paradigm for management of congenital diaphragmatic hernia (CDH), few studies have examined the effect of incremental changes in operative timing on patient outcomes. We hypothesized that later repair would be associated with higher morbidity and mortality., Methods: Data were queried from the CDH Study Group (CDHSG) from 2007-2020. Patients with chromosomal or cardiac abnormalities and those who were never repaired or required pre-repair extra-corporeal life support (ECLS) were excluded. Time to repair was analyzed both as a continuous variable and by splitting the cohort into top/bottom percentiles. The primary outcome of interest was in-hospital mortality. Secondary outcomes included need for and duration of post-repair ventilatory and nutritional support., Results: A total of 4,104 CDH infants were included. Median time to repair was 4 days (IQR 2-6). On multivariable analysis, high-risk (CDHSG stage C/D) defects and lower birthweight predicted later repair. Overall, in-hospital mortality was 6%. On univariate analysis, there was no difference in the number of days to repair between survivors and non-survivors. On risk-adjusted analysis, single-day changes in day of repair were not associated with increased mortality. Later repair was associated with longer time to reach full oral feeds, increased post-repair ventilator days, and increased need for tube feeds and supplementary oxygen at discharge., Conclusions: For infants with isolated CDH not requiring pre-operative ECLS, there is no difference in mortality based on timing of repair, but single-day delays in repair are associated with increased post-repair duration of ventilatory and nutritional support.
- Published
- 2022
- Full Text
- View/download PDF
4. Structure-based protein-ligand interaction fingerprints for binding affinity prediction.
- Author
-
Wang DD, Chan MT, and Yan H
- Abstract
Binding affinity prediction (BAP) using protein-ligand complex structures is crucial to computer-aided drug design, but remains a challenging problem. To achieve efficient and accurate BAP, machine-learning scoring functions (SFs) based on a wide range of descriptors have been developed. Among those descriptors, protein-ligand interaction fingerprints (IFPs) are competitive due to their simple representations, elaborate profiles of key interactions and easy collaborations with machine-learning algorithms. In this paper, we have adopted a building-block-based taxonomy to review a broad range of IFP models, and compared representative IFP-based SFs in target-specific and generic scoring tasks. Atom-pair-counts-based and substructure-based IFPs show great potential in these tasks., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Author(s).)
- Published
- 2021
- Full Text
- View/download PDF
5. When dessert comes close: The effects of anticipating indulgent consumption and dietary restraint on healthy food preference at restaurants.
- Author
-
Oh GG
- Abstract
When dining in restaurants, diners often anticipate indulgent consumption, such as enjoying a dessert. This study examined the effects of anticipating such indulgence on preferences for healthy food among restrained and unrestrained eaters. Two experiments revealed that anticipating indulgent consumption reduced restrained eaters' preference for the immediate consumption of healthy food. Conversely, unrestrained eaters' expectation of indulgent consumption increased or did not change their preference for a healthy option. The interactive effect of indulgence anticipation and dietary restraint on healthy food preference held regardless of availability of nutrition information. The findings suggest that, despite increasing concern for healthy eating, restrained consumers ironically show a preference for unhealthy food options when anticipating a dessert consumption opportunity. The present study provides theoretical implications for consumption anticipation, sequential consumption, and dietary restraint, and practical implications for restaurateurs as well as for consumers, health professionals, and policymakers regarding healthy eating., Competing Interests: None., (© 2020 Elsevier Ltd. All rights reserved.)
- Published
- 2020
- Full Text
- View/download PDF
6. Strategy implementation research in hospitality and tourism: Current status and future potential.
- Author
-
Aladag OF, Köseoglu MA, King B, and Mehraliyev F
- Abstract
To achieve their business objectives, hospitality and tourism organizations need effective implementation as well as consistent strategy formulation. However, the implementation aspect of strategy has attracted relatively less scholarly interest than strategic planning despite its critical role in achieving performance outcomes. Consequently, it is timely to provide an in-depth analysis of the strategy implementation literature. This is particularly the case in hospitality and tourism management where comprehensive literature reviews of strategy implementation have been lacking. To address the knowledge gap, the authors conduct a systematic literature review of 139 articles that appeared in 42 journals over the period 1988-2019. The items were grouped into six topic clusters with a view to generating novel research questions that have the potential to advance the field. We identify four main gaps that should be addressed and suggest prospective research directions., (© 2020 Elsevier Ltd. All rights reserved.)
- Published
- 2020
- Full Text
- View/download PDF
7. Abemaciclib, a potent cyclin-dependent kinase 4 and 6 inhibitor, for treatment of ER-positive metastatic breast cancer.
- Author
-
Lee KA, Shepherd ST, and Johnston SR
- Subjects
- Aminopyridines administration & dosage, Animals, Benzimidazoles administration & dosage, Breast Neoplasms metabolism, Breast Neoplasms pathology, Drug Evaluation, Female, Follow-Up Studies, Humans, Mice, Neoplasm Metastasis, Piperazines administration & dosage, Prognosis, Purines administration & dosage, Pyridines administration & dosage, Survival Rate, Tumor Cells, Cultured, Xenograft Model Antitumor Assays, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Breast Neoplasms drug therapy, Cyclin-Dependent Kinase 4 antagonists & inhibitors, Cyclin-Dependent Kinase 6 antagonists & inhibitors, Molecular Targeted Therapy, Receptors, Estrogen metabolism
- Abstract
CDK 4/6 inhibitors have given patients with estrogen receptor (ER)-positive/HER2-negative (ER+/HER2ࢤ) advanced metastatic breast cancer important new therapeutic options. Abemaciclib is different to the other two licensed and approved CDK 4/6 inhibitors, palbociclib and ribociclib, both in dosing schedule (continuous vs intermittent) and toxicity profile (less neutropenia, more diarrhea), yet the magnitude of clinical benefit seen in first- and second-line studies is very similar. One of the key issues for clinicians is when to use these therapies. Ultimately, the biggest impact of abemaciclib could be in the adjuvant setting if the current MONARCH-E trial in high-risk node-positive patients is positive. The emerging biomarker work in the early breast cancer setting (i.e., neoMONARCH) may determine which tumors are most sensitive to abemaciclib.
- Published
- 2019
- Full Text
- View/download PDF
8. Is mesenteric defect closure needed in urologic surgery using ileum?
- Author
-
Avallone MA, Dietrich PN, Shepherd ST, Lalehzari M, O'Connor RC, and Guralnick ML
- Subjects
- Aged, Anastomosis, Surgical methods, Cohort Studies, Cystectomy adverse effects, Female, Follow-Up Studies, Humans, Ileum surgery, Intestinal Obstruction prevention & control, Intraoperative Complications diagnosis, Intraoperative Complications surgery, Male, Mesentery injuries, Middle Aged, Retrospective Studies, Risk Assessment, Tissue and Organ Harvesting, Treatment Outcome, Urinary Diversion adverse effects, Cystectomy methods, Ileum transplantation, Mesentery surgery, Plastic Surgery Procedures methods, Urinary Diversion methods
- Abstract
Introduction: Classic surgical teaching advocates for closure of the mesenteric defect (MD) after bowel anastomosis but the necessity is controversial. We sought to evaluate the necessity of MD closure at the time of harvest of ileum for genitourinary reconstructive surgery (GURS) by analyzing the incidence of early and late gastrointestinal adverse events (GIAE) in patients with and without MD closure., Materials and Methods: A retrospective review was conducted on patients undergoing urologic reconstruction with ileum to identify incidence of ileus, small bowel obstruction (SBO), gastrointestinal (GI) fistula and stoma complications. Patient and procedure variables were analyzed to identify risk factors for GIAE., Results: A total of 288 patients met inclusion criteria and 93% of GURS was for urinary diversion following cystectomy. MD was closed in 194 cases (67%). Median follow up was 19 months. Early (< 30 day) GIAE rates were 16.5% (n = 32) and 21.3% (n = 20) in the closure and non-closure groups, respectively (p = 0.22). The rate of early ileus/SBO requiring nasogastric tube decompression or laparotomy were similar after closure (15.0%) and non-closure (21.3%) (p = .18). The late GIAE rates were 5.7% (n = 11) and 6.4% (n = 6) in the closure and non-closure cohorts, respectively (p = 0.56). The rate of late SBO were similar and no cases of early or late SBO in either cohort were due to internal herniation. On multivariate analysis, increasing BMI was associated with both early and late GIAE., Conclusions: After harvesting ileum for urologic reconstruction, the MD can safely be left open as we found no association between non-closure and early or late GIAE..
- Published
- 2018
9. Response to: 'Letter to the editor, European Journal of Cancer', commenting on 'Performance of formulae based estimates of glomerular filtration rate for carboplatin dosing in stage 1 seminoma'.
- Author
-
Shepherd ST, Macpherson IR, White JD, and Mark PB
- Subjects
- Humans, Male, Carboplatin therapeutic use, Glomerular Filtration Rate, Seminoma drug therapy, Testicular Neoplasms drug therapy
- Published
- 2014
- Full Text
- View/download PDF
10. Performance of formulae based estimates of glomerular filtration rate for carboplatin dosing in stage 1 seminoma.
- Author
-
Shepherd ST, Gillen G, Morrison P, Forte C, Macpherson IR, White JD, and Mark PB
- Subjects
- Adult, Antineoplastic Agents administration & dosage, Antineoplastic Agents pharmacokinetics, Antineoplastic Agents therapeutic use, Area Under Curve, Body Mass Index, Body Surface Area, Carboplatin administration & dosage, Carboplatin pharmacokinetics, Chelating Agents administration & dosage, Chelating Agents pharmacokinetics, Dose-Response Relationship, Drug, Edetic Acid administration & dosage, Edetic Acid pharmacokinetics, Humans, Male, Middle Aged, Neoplasm Staging, Renal Insufficiency, Chronic drug therapy, Renal Insufficiency, Chronic physiopathology, Seminoma pathology, Testicular Neoplasms pathology, Carboplatin therapeutic use, Glomerular Filtration Rate, Seminoma drug therapy, Testicular Neoplasms drug therapy
- Abstract
Background: Single cycle carboplatin, dosed by glomerular filtration rate (GFR), is standard adjuvant therapy for stage 1 seminoma. Accurate measurement of GFR is essential for correct dosing. Isotopic methods remain the gold standard for the determination of GFR. Formulae to estimate GFR have improved the assessment of renal function in non-oncological settings. We assessed the utility of these formulae for carboplatin dosing., Methods: We studied consecutive subjects receiving adjuvant carboplatin for stage 1 seminoma at our institution between 2007 and 2012. Subjects underwent 51Cr-ethylene diamine tetra-acetic acid (EDTA) measurement of GFR with carboplatin dose calculated using the Calvert formula. Theoretical carboplatin doses were calculated from estimated GFR using Chronic Kidney Disease-Epidemiology (CKD-EPI), Management of Diet in Renal Disease (MDRD) and Cockcroft-Gault (CG) formulae with additional correction for actual body surface area (BSA). Carboplatin doses calculated by formulae were compared with dose calculated by isotopic GFR; a difference <10% was considered acceptable., Results: 115 patients were identified. Mean isotopic GFR was 96.9 ml/min/1.73 m(2). CG and CKD-EPI tended to overestimate GFR whereas MDRD tended to underestimate GFR. The CKD-EPI formula had greatest accuracy. The CKD-EPI formula, corrected for actual BSA, performed best; 45.9% of patients received within 10% of correct carboplatin dose. Patients predicted as underdosed (13.5%) by CKD-EPI were more likely to be obese (p=0.013); there were no predictors of the 40.5% receiving an excess dose., Conclusions: Our data support further evaluation of the CKD-EPI formula in this patient population but clinically significant variances in carboplatin dosing occur using non-isotopic methods of GFR estimation. Isotopic determination of GFR should remain the recommended standard for carboplatin dosing when accuracy is essential., (Copyright © 2014 Elsevier Ltd. All rights reserved.)
- Published
- 2014
- Full Text
- View/download PDF
11. Small RNAs control sodium channel expression, nociceptor excitability, and pain thresholds.
- Author
-
Zhao J, Lee MC, Momin A, Cendan CM, Shepherd ST, Baker MD, Asante C, Bee L, Bethry A, Perkins JR, Nassar MA, Abrahamsen B, Dickenson A, Cobb BS, Merkenschlager M, and Wood JN
- Subjects
- Analysis of Variance, Animals, Cerebellum cytology, Core Binding Factor Alpha 2 Subunit genetics, Core Binding Factor Alpha 2 Subunit metabolism, DEAD-box RNA Helicases deficiency, Disease Models, Animal, Endoribonucleases deficiency, Female, Freund's Adjuvant adverse effects, Ganglia, Spinal metabolism, Gene Expression Profiling methods, Male, Mice, Mice, Knockout, MicroRNAs physiology, NAV1.8 Voltage-Gated Sodium Channel, Nerve Tissue Proteins metabolism, Oligonucleotide Array Sequence Analysis methods, Pain chemically induced, Pain genetics, Pain Measurement, Proto-Oncogene Proteins c-fos metabolism, Receptors, Purinergic P2 genetics, Receptors, Purinergic P2 metabolism, Receptors, Purinergic P2X3, Ribonuclease III, Sodium Channels deficiency, Sodium Channels genetics, Spinal Cord physiopathology, Time Factors, Gene Expression Regulation genetics, Nociceptors metabolism, Pain physiopathology, Pain Threshold physiology, Sensory Receptor Cells physiology, Sodium Channels metabolism
- Abstract
To examine the role of small RNAs in peripheral pain pathways, we deleted the enzyme Dicer in mouse postmitotic damage-sensing neurons. We used a Nav1.8-Cre mouse to target those nociceptors important for inflammatory pain. The conditional null mice were healthy with a normal number of sensory neurons and normal acute pain thresholds. Behavioral studies showed that inflammatory pain was attenuated or abolished. Inflammatory mediators failed to enhance excitability of Nav1.8+ sensory neurons from null mutant mice. Acute noxious input into the dorsal horn of the spinal cord was apparently normal, but the increased input associated with inflammatory pain measured using c-Fos staining was diminished. Microarray and quantitative real-time reverse-transcription PCR (qRT-PCR) analysis showed that Dicer deletion lead to the upregulation of many broadly expressed mRNA transcripts in dorsal root ganglia. By contrast, nociceptor-associated mRNA transcripts (e.g., Nav1.8, P2xr3, and Runx-1) were downregulated, resulting in lower levels of protein and functional expression. qRT-PCR analysis also showed lowered levels of expression of nociceptor-specific pre-mRNA transcripts. MicroRNA microarray and deep sequencing identified known and novel nociceptor microRNAs in mouse Nav1.8+ sensory neurons that may regulate nociceptor gene expression.
- Published
- 2010
- Full Text
- View/download PDF
12. Dexmedetomidine versus propofol/midazolam for long-term sedation during mechanical ventilation.
- Author
-
Ruokonen E, Parviainen I, Jakob SM, Nunes S, Kaukonen M, Shepherd ST, Sarapohja T, Bratty JR, and Takala J
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Double-Blind Method, Female, Humans, Intensive Care Units, Male, Middle Aged, Pilot Projects, Time Factors, Young Adult, Dexmedetomidine administration & dosage, Hypnotics and Sedatives administration & dosage, Midazolam administration & dosage, Propofol administration & dosage, Respiration, Artificial psychology
- Abstract
Purpose: To compare dexmedetomidine (DEX) with standard care (SC, either propofol or midazolam) for long-term sedation in terms of maintaining target sedation and length of intensive care unit (ICU) stay., Methods: A pilot, phase III, double-blind multicenter study in randomized medical and surgical patients (n = 85) within the first 72 h of ICU stay with an expected ICU stay of >or=48 h and sedation need for >or=24 h after randomization. Patients were assigned to either DEX (
- Published
- 2009
- Full Text
- View/download PDF
13. The preparation of fully active chymopapain free of contaminating proteinases.
- Author
-
Buttle DJ, Dando PM, Coe PF, Sharp SL, Shepherd ST, and Barrett AJ
- Subjects
- Binding Sites, Chromatography, Affinity, Cysteine Endopeptidases, Enzyme Activation, Hydrogen-Ion Concentration, Hydrolysis, Iodoacetates, Iodoacetic Acid, Kinetics, Mercuric Chloride, Peptide Hydrolases, Chymopapain isolation & purification, Latex chemistry, Plants enzymology
- Abstract
Chymopapain (EC 3.4.22.6) was purified from commercially available dried latex of papaya (Carica papaya) by extraction at acidic pH, cation-exchange chromatography and active site-directed affinity chromatography on immobilized alanyl-phenyl-alaninaldehyde semicarbazone, with elution by mercuric chloride. The product was found by immunoassay to be essentially free of the other cysteine proteinases from papaya, including papaya proteinase IV, and was fully active. The rate of alkylation of the active site cysteine of chymopapain by iodoacetate was found to be sufficiently rapid and selective for this reagent to be used as an active-site titrant.
- Published
- 1990
- Full Text
- View/download PDF
14. The separation and properties of two penicillin-binding proteins from Salmonella typhimurium.
- Author
-
Shepherd ST, Chase HA, and Reynolds PE
- Subjects
- Carboxypeptidases metabolism, Cell Membrane metabolism, Chromatography, Affinity, Kinetics, Molecular Weight, Penicillin G pharmacology, Spheroplasts metabolism, Carrier Proteins isolation & purification, Carrier Proteins metabolism, Penicillin G metabolism, Salmonella typhimurium metabolism
- Published
- 1977
- Full Text
- View/download PDF
15. Identification of the binding protein which may be the target of penicillin action in Bacillus megaterium.
- Author
-
Reynolds PE, Shepherd ST, and Chase HA
- Subjects
- Bacillus megaterium drug effects, Bacillus megaterium growth & development, Membrane Proteins metabolism, Penicillin G pharmacology, Bacillus megaterium metabolism, Bacterial Proteins metabolism, Carrier Proteins metabolism, Penicillin G metabolism
- Published
- 1978
- Full Text
- View/download PDF
16. Studies on the penicillin-binding components of Bacillus megaterium.
- Author
-
Chase HA, Shepherd ST, and Reynolds PE
- Subjects
- Bacillus megaterium drug effects, Binding, Competitive, Cephaloridine pharmacology, Cephalothin pharmacology, Molecular Weight, Bacillus megaterium metabolism, Carrier Proteins metabolism, Penicillin G metabolism
- Published
- 1977
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.