bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of Cholinesterases From Multiple Large Animal Species for Medical Countermeasure Development Against Chemical Warfare Nerve Agents
Authors: McGarry Kevin G , Schill Kevin E , Winters Tyson P , Lemmon Erin E , Sabourin Carol L , Harvilchuck Jill A , Moyer Robert A 
Published: December 2019

Abstract
Organophosphorus (OP) compounds, which include insecticides and chemical warfare nerve agents (CWNAs) such as sarin (GB) and VX, continue to be a global threat to both civilian and military populations. It is widely accepted that cholinesterase inhibition is the primary mechanism for acute OP toxicity. Disruption of cholinergic function through the inhibition of acetylcholinesterase (AChE) leads to the accumulation of the neurotransmitter acetylcholine. Excess acetylcholine at the synapse results in an overstimulation of cholinergic neurons which manifests in the common signs and symptoms of OP intoxication (miosis, increased secretions, seizures, convulsions, and respiratory failure). The primary therapeutic strategy employed in the United States to treat OP intoxication includes reactivation of inhibited AChE with the oxime pralidoxime (2-PAM) along with the muscarinic acetylcholine receptor antagonist atropine and the benzodiazepine, diazepam. CWNAs are also known to inhibit butyrylcholinesterase (BChE) without any apparent toxic effects. Therefore, BChE may be viewed as a “bioscavenger” that stoichiometrically binds CWNAs and removes them from circulation. The degree of inhibition of AChE and BChE and the effectiveness of 2-PAM are known to vary among species. Animal models are imperative for evaluating the efficacy of CWNA medical countermeasures, and a thorough characterization of available animal models is important for translating results to humans. Thus, the objective of this study was to compare the circulating levels of each of the cholinesterases as well as multiple kinetic properties (inhibition, reactivation, and aging rates) of both AChE and BChE derived from humans to AChE and BChE derived from commonly used large animal models.
[18F] FBB cortical uptake is not related to the age of onset of Alzheimer’s disease
Authors: Chiaravalloti Agostino , Barbagallo Gaetano , Castellano Anna Elisa , Ricci Maria , Ciccariello Gabriele , Ursini Francesco , D’Ascenzo Nicola , Xie Quingguo , Schillaci Orazio 
Published: December 2019

Aim
To investigate the relationships between amyloid burden in brain and the age of onset of Alzheimer’s disease.

Materials and methods
We examined 60 patients with clinical diagnosis of Alzheimer’s disease. Of them, 22 were early-onset of Alzheimer’s disease and 38 were late-onset of Alzheimer’s disease. All of them underwent a brain PET scan 90 minutes after the injection of 4-[(E)-2-[4-[2-[2-(2-fluoranylethoxy)ethoxy]ethoxy]phenyl]ethenyl]-N-methylaniline ([18F] FBB); 300 ± 10 MBq). Relationships between amyloid burden in brain and age of onset of Alzheimer’s disease were assessed by means of statistical parametric mapping version 12.

Results
There were no significant differences [18F] FBB uptake between early-onset of Alzheimer’s disease and late-onset of Alzheimer’s disease patients.

Conclusion
In our study group, the age of onset is not related to brain amyloid burden in Alzheimer’s disease patients.
Pediatric Colonoscopic Polypectomy Technique
Authors: Kay Marsha , Wyllie Robert 
Published: December 2019

ABSTRACTColonoscopy with polypectomy is frequently performed in pediatric patients based on symptoms, with the majority of polyps identified being benign juvenile pedunculated polyps with a vascular stalk. This is in distinction to adults where polypectomy is often performed as part of a colon cancer screening and prevention strategy and a higher fraction of polyps are sessile and or dysplastic. In adults, polypectomy techniques emphasize a need for deeper resection to ensure complete resection of adenomas or potential carcinoma in situ. Adenomatous polyps can occur in the pediatric age group and may be associated with an underlying polyposis, hereditary or chronic inflammatory conditions. Polypectomy techniques include use of cold biopsy forceps for very small polyps, cold snare polypectomy for small sessile polyps and hot snare polypectomy for the majority of polyps in the pediatric age group. Adjuvant techniques include epinephrine volume reduction, saline‐assisted polypectomy and hemostatic techniques including injection, clip application and loop application to prevent or treat post‐polypectomy bleeding. Electrosurgical principles guide the settings and type of current utilized during hot snare polypectomy. Polypectomy utilizing thermal techniques is associated with a higher risk of complications compared with diagnostic colonoscopy.
Economic Impact and Prognostic Factors of Functional Dyspepsia in Children
Authors: Mani Jyoti , Madani Shailender , Thomas Ron 
Published: December 2019

ABSTRACTObjectives:Functional dyspepsia (FD) is a functional abdominal pain disorder. There is paucity of data on the economic impact of FD in children. Primary aim of our study was to estimate annual evaluation cost (“diagnosis and visit” cost) and secondary aim was to identify potential prognostic factors of FD in children.Methods:Out of the 136 patients 86 met inclusion criteria and were divided into 2 clinical groups: Complete Improvement Group (CIG‐30 patients) and Partial/No Improvement Group (PIG/NIG‐56 patients). Medications used were noted descriptively. Annual evaluation cost was calculated using 2017 Medicare reimbursement rates.Results:Annual evaluation cost in all patients was $724.874 ± $180.075 ($544.799 ± $87.995 in CIG and $904.949 ± 79.083 in PIG/NIG). An extrapolated annual cost of evaluation in children with FD would be approximately $5.79 billion. Average number of clinic visits (3.1 ± 1.2 in CIG vs 4.40 ± 3.1 in PIG/NIG), duration of follow‐up in months (9.2 ± 6.6 in CIG vs 17.1 ± 13.6 in PIG/NIG), use of imaging studies (7 patients in CIG [23.3%] vs 29 in PIG/NIG [51.8%]) and endoscopic procedures (17 in CIG [56.7%] vs 46 in PIG/NIG [82.1%]) were significantly higher in PIG/NIG (P < 0.005). PIG/NIG required multiple medications for control of symptoms compared to CIG (4 patients in CIG [13.5%] vs 30 in PIG [53.6%], P value <0.001]. For every $500.00 decrease in total evaluation cost the odds of having a complete response was 0.998 (P = 0.027). No prognostic factors were identified in children with FD.Conclusions:FD in children has a significant economic impact on health care expenditure. Patients with FD who have partial/no response to treatment incur greater financial cost potentially adding to health care expenditure.
Enhanced Recovery after Surgery Protocols Decrease Outpatient Opioid Use in Patients Undergoing Abdominally Based Microsurgical Breast Reconstruction
Authors: Rendon Juan L. , Hodson Trevor , Skoracki Roman J. , Humeidan Michelle , Chao Albert H. 
Published: December 2019

Background:
Enhanced recovery after surgery (ERAS) protocols have known benefits in the inpatient setting, but little is known about their impact in the subsequent outpatient setting. On discharge, multimodal analgesia has been discontinued, nerve blocks and pain pumps have worn off, and patients enter a substantially different physical environment, potentially resulting in a rebound effect. The objective of this study was to investigate the effect of ERAS protocol implementation on outpatient opioid use and recovery.

Methods:
Patients who underwent abdominally based microsurgical breast reconstruction before and after ERAS implementation were reviewed retrospectively. Ohio state law mandates that no more than 7 days of opioids may be prescribed at a time, with the details of all prescriptions recorded in a statewide reporting system, from which opioid use was determined.

Results:
A total of 105 patients met inclusion criteria, of which 46 (44 percent) were in the pre-ERAS group and 59 (56 percent) were in the ERAS group. Total outpatient morphine milligram equivalents used in the ERAS group were less than in the pre-ERAS group (337.5 morphine milligram equivalents versus 668.8 morphine milligram equivalents, respectively; p =0.016). This difference was specifically significant at postoperative week 1 (p =0.044), with gradual convergence over subsequent weeks. Although opioid use was significantly less in the ERAS group, pain scores in the ERAS group were comparable to those in the pre-ERAS group.

Conclusions:
The benefits of ERAS protocols appear to extend into the outpatient setting, further supporting their use to facilitate recovery, and highlighting their potential role in helping to address the prescription opioid abuse problem.

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Therapeutic, III.
Dupuytren’s Disease Predicts Increased All-Cause and Cancer-Specific Mortality: Analysis of a Large Cohort from the U.K. Clinical Practice Research Datalink
Authors: Kuo Rachel Yi Ling , Ng Michael , Prieto-Alhambra Daniel , Furniss Dominic 
Published: December 2019

Background:
Dupuytren’s disease is a common, chronic, fibroproliferative disease of the palmar fascia. The cause is unclear but includes genetic predisposition alongside environmental factors. Several studies have suggested an association between Dupuytren’s disease and excess mortality. The authors aimed to evaluate this association in adult patients in the United Kingdom and identify the causes of mortality.

Methods:
The authors used a large primary care database (Clinical Practice Research Datalink) linked to the Office of National Statistics to identify patients with Dupuytren’s disease between January 1, 1995, and December 31, 2013. Each patient was matched by age, sex, and general practitioner to five control patients without the disease. Cox regression models were used to study the association between Dupuytren’s disease and all-cause and cause-specific mortality, adjusting for confounders.

Results:
A total of 41,965 Dupuytren’s disease patients and 209,825 control patients were identified. The all-cause mortality rate was increased in both unadjusted (hazard ratio, 1.48; 99% CI, 1.29 to 1.70; p < 0.0001) and multivariable adjusted (hazard ratio, 1.43; 99% CI, 1.25 to 1.65; p < 0.0001) models in patients with Dupuytren’s disease, 12 years after diagnosis. Excess mortality was secondary to a wide range of causes, including cancer (hazard ratio, 1.66; 99% CI, 1.27 to 2.17; p < 0.0001), an effect that persisted after adjustment for confounders.

Conclusions:
There is excess mortality associated with Dupuytren’s disease that can be partially explained through environmental factors. From time of diagnosis in primary care, there is a 12-year window of opportunity for intervention to reduce the impact of these factors. The authors observed an increased risk of cancer mortality independent of confounders, and hypothesize a shared genetic risk between Dupuytren’s disease and cancer.

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Risk, II.
Surgical Correction of Breast Animation Deformity with Implant Pocket Conversion to a Prepectoral Plane
Authors: Holland Michael C. , Lentz Rachel , Sbitany Hani 
Published: December 2019

Background:
Animation deformity is an undesirable outcome of subpectoral breast reconstruction that results in abnormal breast contraction with activity, breast pain, and increased implant visibility. Surgical correction requires implant removal and conversion of the reconstruction to a prepectoral plane. The authors present their institutional experience with their preferred surgical technique to treat this challenging problem and outline solutions for increased success in these patients.

Methods:
A retrospective review was performed of all patients undergoing conversion of their subpectoral breast reconstruction to a prepectoral plane at the authors’ institution. Patient demographics and surgical details were analyzed, and postoperative outcomes and morbidity were assessed. The effects of changing operative strategies on enhanced success are also reported.

Results:
A total of 80 breast conversions were performed over a 2.5-year period. All patients demonstrated resolution of animation deformity at a mean follow-up of 15.2 months. Two reconstructions (2.5 percent) required an unplanned return to the operating room, and 11 reconstructions (13.8 percent) were treated for infection. Preconversion fat grafting and the use of acellular dermal matrix were both associated with a reduced incidence of postoperative asymmetry and capsular contracture (p < 0.05). There were no reconstructive failures associated with conversion to a prepectoral pocket.

Conclusions:
Treatment of animation deformity in the reconstructed patient can be safely performed by surgical conversion to a prepectoral plane. The use of acellular dermal matrix, and preconversion fat grafting, in appropriate patients can improve results. The authors promote this operative algorithm for all reconstructive patients experiencing symptomatic animation deformity with subpectoral breast reconstruction.

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Therapeutic, IV.
Differential Responsiveness to BMP9 between Patent and Fused Suture Progenitor Cells from Craniosynostosis Patients
Authors: Song Dongzhe , Huang Shifeng , Zhang Linghuan , Liu Wei , Huang Bo , Feng Yixiao , Liu Bo , He Tong-Chuan , Huang Dingming , Reid Russell R. 
Published: December 2019

Background:
Several studies have verified that bone morphogenetic proteins (BMPs) may be involved in the development of craniosynostosis; little attention has been focused on the role of BMP9 in cranial suture biology. The authors investigated the role of BMP9 in suture progenitor cells.

Methods:
The authors isolated and cultured prematurely fused and internal control patent suture progenitor cells from patients with nonsyndromic craniosynostosis. Overexpression of BMP9 was mediated by adenoviral vectors. Osteoblast and osteoclast differentiation-related markers were evaluated by staining techniques and touchdown quantitative polymerase chain reaction analysis. In vivo analysis of BMP9-induced suture progenitor cell osteogenesis was performed in an ectopic bone formation model.

Results:
The authors demonstrated that the prematurely fused sutures have a higher endogenous expression of the osteogenic differentiation-related genes than patent sutures, whereas the same pattern of gene expression exists between fused and patent suture progenitor cells. Importantly, both patent and fused suture progenitor cells undergo osteogenic differentiation and express multiple lineage regulators and NELL-1 on BMP9 stimulation, whereas fused suture progenitor cells have a higher basal osteogenic potential than patent suture progenitor cells. BMP9 regulates the expression of osteoclast differentiation-related genes in suture progenitor cells. Forced BMP9 expression enhances the mineralization and maturity of ectopic bone formation of suture progenitor cells implanted in vivo.

Conclusions:
The authors’ findings suggest that fused suture progenitor cells have elevated osteogenic potential. BMP9 could regulate the expression of multiple osteoblast and osteoclast differentiation-related genes, and NELL-1, in both suture progenitor cells, indicating that BMP9 may play a role in craniosynostosis.
Indications and Limitations of Bilayer Wound Matrix–Based Lower Extremity Reconstruction: A Multidisciplinary Case-Control Study of 191 Wounds
Authors: Shakir Sameer , Messa Charles A. , Broach Robyn B. , Rhemtulla Irfan A. , Chatman Brett , D’Angelantonio Albert , Levin L. Scott , Kovach Stephen J. , Serletti Joseph M. , Fischer John P. 
Published: December 2019

Background:
Little is known about the efficacy of newer skin substitute scaffolds to reconstruct complex lower extremity wounds. The investigators present a multihospital experience of reconstructive surgeons utilizing collagen-GAG bilayer wound matrix in lower extremity soft-tissue reconstruction with the goals to (1) characterize a suitable patient population, (2) categorize failures to optimize patient selection, and (3) determine wound factors affecting success.

Methods:
Subjects underwent collagen-GAG–based lower extremity wound reconstruction from May of 2010 to June of 2017. The primary outcome variable was 180-day graft success, defined as eventual split-thickness skin grafting after bilayer wound matrix application; failure was defined as inadequate wound bed for split-thickness skin grafting, requirement for vascularized tissue transfer, or eventual amputation. Eligible subjects had at least one lower extremity wound and were at least 18 years old. Exclusion criteria included third-degree burn wounds or failure to follow up for at least 60 days postoperatively. Predictor variables included demographics, medical comorbidities, perioperative characteristics, postoperative complications, and cost-related data for each hospitalization.

Results:
There were 147 subjects with 191 wounds. Mean patient age was 60.1 years (range, 21.0 to 95.6 years), and mean body mass index was 30.5 kg/m2 (range, 14.4 to 64.7 kg/m2). Average wound size was 73.1 ± 137.7 cm2, with 49.0 percent of subjects receiving adjunct postoperative negative-pressure wound therapy. Seventy percent of wounds were successfully healed at 180 days. Most were localized between the knee and ankle (50.8 percent) or foot (46.1 percent). Tendon exposure (p < 0.05), bone exposure (p < 0.01), and bone excision (p < 0.04) were associated with reconstructive failure.

Conclusions:
The authors present the largest reported multihospital, multidisciplinary experience with collagen-GAG wound matrix for lower extremity reconstruction. Tendon and/or bone exposure and socioeconomic factors were associated with failure.

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Risk, III.
Challenges in the Successful Reconstruction of Cleft Lip and Palate: Managing the Nasomaxillary Deformity in Adolescence
Authors: Posnick Jeffrey C. , Kinard Brian E. 
Published: December 2019

Summary:
The surgical techniques and execution of primary cleft lip and palate repair are no longer the greatest challenge to achieving successful rehabilitation for those born with facial clefting (i.e., bilateral and unilateral cleft lip and palate). Despite a surgeon’s best efforts, when cleft palate repair is carried out during infancy, by the mixed dentition, a majority will demonstrate nasomaxillary deficiency. The cleft team’s commitment to a family under their care is to ensure that the newborn reaches adulthood reconstructed without need for special regard to their original birth malformation. Guiding principles are provided for the accurate diagnosis and reliable reconstruction of the bilateral and unilateral cleft lip and palate adolescent/adult who presents with nasomaxillary deficiency and any residual oronasal fistula, bony defects, cleft dental gap(s), nasal obstructions, and associated facial dysmorphology. Successful orthognathic surgery provides a stable foundation on which any remaining soft-tissue cleft lip or cleft nasal deformities can be accurately assessed and then reconstructed.
Design of a 3-Arm Randomized Trial for Posthysterectomy Vault Prolapse Involving Sacral Colpopexy, Transvaginal Mesh, and Native Tissue Apical Repair: The Apical Suspension Repair for Vault Prolapse in a Three-Arm Randomized Trial
Authors: Menefee Shawn , Richter Holly E. , Myers Deborah , Weidner Alison , Moalli Pamela , Harvie Heidi , Rahn David , Jeppson Peter , Paraiso Marie , Thomas Sonia , Mazloomdoost Donna 
Published: December 2019

Objective
The objective of this study was to present the design of the Apical Suspension Repair for Vault Prolapse in a Three-Arm Randomized Trial (ASPIRe), which compares the efficacy and safety of 3 apical repairs: native tissue (NT) transvaginal repair, transvaginal mesh, and sacral colpopexy.

Methods
Patient selection criteria, primary and secondary outcome measures including patient-reported outcome questionnaires, masking, surgeon certification, procedure standardization, adverse events collection and adjudication, and cost analysis will be described for this multi-centered randomized trial. Given the unique risks/benefits of each technique, a noninferiority design will be used to compare apical transvaginal mesh to mesh sacral colpopexy. A superiority design will be used to compare the 2 mesh repairs to NT transvaginal apical repair. Survival analysis will be used to assess a composite primary outcome for success composed of a subjective measure (no prolapse symptoms), objective measure (no prolapse beyond the hymen), and no prolapse retreatment, with a minimum follow-up of 36 months. Secondary outcome measures collected every 6 months include assessment of validated general and condition-specific quality of life measures, global impression of improvement, satisfaction and regret, body image, and sexual function.

Results
Randomization and surgical treatment of 360 participants are complete, and the study is in the follow-up phase.

Conclusions
This report will provide valuable insight on the design of a novel 3-arm surgical trial using mesh versus NT to repair vaginal vault prolapse. This trial will provide level 1 evidence on the risks and benefits of mesh augmented versus NT apical repairs.
The rise of diversity in metabolic platforms across the Candidate Phyla Radiation
Authors: Jaffe Alexander L. , Castelle Cindy J. , Matheus Carnevali Paula B. , Gribaldo Simonetta , Banfield Jillian F. 
Published: December 2019

ABSTRACTA unifying feature of the bacterial Candidate Phyla Radiation (CPR) is a limited and highly variable repertoire of biosynthetic capabilities. However, the distribution of metabolic traits across the CPR and the evolutionary processes underlying them are incompletely resolved. Here, we selected ∼1,000 genomes of CPR bacteria from diverse environments to construct a robust internal phylogeny that was consistent across two unlinked marker sets. Mapping of glycolysis, the pentose phosphate pathway, and pyruvate metabolism onto the tree showed that some components of these pathways are sparsely distributed and that similarity between metabolic platforms is only partially predicted by phylogenetic relationships. To evaluate the extent to which gene loss and lateral gene transfer have shaped trait distribution, we analyzed the patchiness of gene presence in a phylogenetic context, examined the phylogenetic depth of clades with shared traits, and compared the reference tree topology with those of specific metabolic proteins. While the central glycolytic pathway in CPR is widely conserved and has likely been shaped primarily by vertical transmission, there is evidence for both gene loss and transfer especially in steps that convert glucose into fructose 1,6-bisphosphate and glycerate 3P into pyruvate. Additionally, the distribution of Group 3 and Group 4-related NiFe hydrogenases is patchy and suggests multiple events of ancient gene transfer. Overall, patterns of gene gain and loss, including acquisition of accessory traits in independent transfer events, may have been driven by shifts in host-derived resources and led to sparse but varied genetic inventories.