bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antifibrinolytic Agents in Plastic Surgery: Current Practices and Future Directions
Authors: Brown Stav , Yao Amy , Taub Peter J. 
Published: May 2018

Background:
Prevention of blood loss is a chief consideration in plastic and reconstructive surgery. The antifibrinolytic drugs tranexamic acid and ε-aminocaproic acid have emerged as promising agents to reduce both perioperative blood loss and transfusion requirements. However, published reports in the plastic surgery literature are lacking. The authors sought to summarize the current knowledge of the use of antifibrinolytics in plastic surgery by reviewing the existing literature for clinical outcomes and recommendations.

Methods:
A systematic review of the PubMed, Cochrane, and Google Scholar databases was conducted for publications examining the use of antifibrinolytics in plastic surgery. Studies were abstracted for procedure type, antifibrinolytic dose, time and mode of administration, blood loss, transfusion requirements, and complications.

Results:
Thirty-three studies were deemed eligible for inclusion, comprising a total of 1823 patients undergoing plastic surgical procedures with tranexamic acid (n = 1328) and/or ε-aminocaproic acid (n = 495).

Conclusions:
Tranexamic acid and ε-aminocaproic acid are widely used to reduce blood loss and transfusion requirements in craniofacial and orthognathic surgery, without an increased risk of adverse events. Intravenous administration is most commonly used, although topical formulations show similar efficacy with a reduced systemic distribution. Tranexamic acid has also emerged as a promising agent in aesthetic surgery and burn care, due to its favorable safety profile and role in reducing blood loss, achieving an improved surgical field, and reducing edema and ecchymosis. Further investigation of these agents in the fields of burn care, aesthetic surgery, and microsurgery is warranted to standardize protocols for clinical use.
Lymphovenous Anastomosis for the Treatment of Chylothorax in Infants: A Novel Microsurgical Approach to a Devastating Problem
Authors: Weissler Jason M. , Cho Eugenia H. , Koltz Peter F. , Carney Martin J. , Itkin Maxim , Laje Pablo , Levin L. Scott , Dori Yoav , Kanchwala Suhail K. , Kovach Stephen J. 
Published: May 2018

Summary:
With the expanding horizon of microsurgical techniques, novel treatment strategies for lymphatic abnormalities are increasingly reported. Described in this article is the first reported use of lymphovenous anastomosis surgery to manage recalcitrant chylothoraces in infants. Chylothorax is an increasingly common postoperative complication after pediatric cardiac surgery, with a reported incidence of up to 9.2 percent in infants. Although conservative nutritional therapy has a reported 70 percent success rate in this patient population, failed conservative management leading to persistent chylothorax is associated with a significant risk of multisystem complications and mortality. Once conservative medical strategies are deemed unsuccessful, surgical or radiologic interventions, such as percutaneous thoracic duct embolization or ligation, are often attempted. However, these procedures lack high-level evidence in the infant population and remain a challenge, given the small size of the lymphatic vessels. As such, we report our experience with performing lymphovenous anastomoses in two infants who had developed refractory chylothoraces secondary to thoracic duct injury following cardiac surgery for congenital cardiac anomalies. In addition, this article reviews the relevant pathophysiology of chylothoraces, current treatment algorithm following failed conservative management, and potential role of the microsurgeon in the multidisciplinary management of this life-threatening problem. As part of the evolving microsurgery frontier, physiologic operations, such as lymphovenous anastomosis, may have a considerable role in the management of refractory pediatric chylothoraces. In our experience, lymphovenous anastomosis can restore normal lymphatic circulation within 1 to 2 weeks, liberate patients from mechanical ventilation, and enable expeditious return to enteral feeding.

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Therapeutic, V.
Brain Correlates of Mental Stress-Induced Myocardial Ischemia
Authors: Bremner J. Douglas , Campanella Carolina , Khan Zehra , Shah Majid , Hammadah Muhammad , Wilmot Kobina , Al Mheid Ibhar , Lima Bruno B. , Garcia Ernest V. , Nye Jonathon , Ward Laura , Kutner Michael H. , Raggi Paolo , Pearce Brad D. , Shah Amit J. , Quyyumi Arshed A. , Vaccarino Viola 
Published: May 2018

ABSTRACT

Objective
Coronary artery disease (CAD) is a major cause of morbidity and mortality, and despite important advances in our understanding of this disorder, the underlying mechanisms remain under investigation. Recently, increased attention has been placed on the role of behavioral factors such as emotional stress on CAD risk. Brain areas involved in memory and the stress response, including medial prefrontal cortex, insula, and parietal cortex, also have outputs to the peripheral cardiovascular system. The purpose of this study was to assess the effects of mental stress on brain and cardiac function in patients with CAD.

Methods
CAD patients (N = 170) underwent cardiac imaging with [Tc-99m] sestamibi single-photon emission tomography at rest and during a public speaking mental stress task. On another day, they underwent imaging of the brain with [O-15] water positron emission tomography (PET) during mental stress (arithmetic and public speaking) and control conditions.

Results
Patients with mental stress–induced myocardial ischemia showed increased activation with stress in anterior cingulate, inferior frontal gyrus, and parietal cortex (p < .005). This was seen with both arithmetic stress and public speaking stress. Arithmetic stress was additionally associated with left insula activation, and public speaking with right pre/postcentral gyrus and middle temporal gyrus activation (p < .005).

Conclusions
These findings suggest that mental stress–induced myocardial ischemia is associated with activation in brain areas involved in the stress response and autonomic regulation of the cardiovascular system. Altered brain reactivity to stress could possibly represent a mechanism through which stress leads to increased risk of CAD-related morbidity and mortality.
Tofacitinib 5 mg Twice Daily in Patients with Rheumatoid Arthritis and Inadequate Response to Disease-Modifying Antirheumatic Drugs
Authors: Bird Paul , Bensen William , El-Zorkany Bassel , Kaine Jeffrey , Manapat-Reyes Bernadette Heizel , Pascual-Ramos Virginia , Witcombe David , Soma Koshika , Zhang Richard , Thirunavukkarasu Krishan 
Published: May 2018

Background
Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). We performed a comprehensive review of phase 3 studies of tofacitinib 5 mg twice daily (BID) (approved dose in many countries) in patients with moderate to severe RA and inadequate response to prior disease-modifying antirheumatic drugs.

Methods
A search of PubMed and ClinicalTrials.gov identified 5 studies: ORAL Solo (NCT00814307), ORAL Sync (NCT00856544), ORAL Standard (included adalimumab 40 mg once every 2 weeks; NCT00853385), ORAL Scan (NCT00847613), and ORAL Step (NCT00960440). Efficacy and safety data for tofacitinib 5 mg BID, placebo, and adalimumab were analyzed.

Results
Across the 5 studies, 1216 patients received tofacitinib 5 mg BID, 681 received placebo, and 204 received adalimumab. At month 3, tofacitinib demonstrated significantly higher 20%, 50%, and 70% improvement in American College of Rheumatology response criteria (ACR20, ACR50, and ACR70, respectively) response rates, greater improvement in Health Assessment Questionnaire-Disability Index, and a higher proportion of Disease Activity Score-defined remission than placebo. Frequencies of adverse events (AEs), serious AEs, and discontinuations due to AEs were similar for tofacitinib and placebo at month 3; serious infection events were more frequent for tofacitinib. In ORAL Standard, although not powered for formal comparisons, tofacitinib and adalimumab had numerically similar efficacy and AEs; serious AEs and serious infection events were more frequent with tofacitinib.

Conclusions
Tofacitinib 5 mg BID reduced RA signs and symptoms and improved physical function versus placebo in patients with inadequate response to prior disease-modifying antirheumatic drugs. Tofacitinib 5 mg BID had a consistent, manageable safety profile across studies, with no new safety signals identified.
Prognostic Value of Lymph Node Yield on Overall Survival in Esophageal Cancer Patients
Authors: Visser Els , Markar Sheraz R. , Ruurda Jelle P. , Hanna George B. , van Hillegersberg Richard 
Published: May 2018

Objective:
This meta-analysis determines whether increased lymph node yield improves survival in patients with esophageal cancer undergoing esophagectomy with or without neoadjuvant therapy.

Background:
Esophagectomy involves resection of the esophagus and surrounding lymph nodes, which are commonly the first stations of cancer spread. The extent of lymphadenectomy during esophagectomy remains controversial, with several studies publishing conflicting results, especially in the era of neoadjuvant therapy.

Methods:
An electronic literature search was undertaken using Embase, Medline, and the Cochrane library databases (2000 to 2017). Articles with esophageal cancer patients undergoing esophagectomy with lymphadenectomy and investigating the effects of low and high lymph node yield on overall survival and disease-free survival were included. Meta-analysis of data was conducted using a random effects model. If the study divided the cohort into multiple groups based on lymph node yield, survival was compared between the lowest and highest lymph node yield groups. In addition to analysis of the entire cohort, subset analysis of only those patients receiving neoadjuvant therapy was also performed.

Results:
A total of 26 studies were included in this meta-analysis with a follow-up ranging from 15 to 94 months. For the analysis of overall survival, 23 studies were included. A meta-analysis showed that overall survival significantly improved in the high lymph node yield group [hazard ratio (HR) = 0.81; 95% confidence interval (95% CI) = 0.74–0.87; P < 0.01]. In the 10 studies describing disease-free survival, this was significantly improved in the high lymph node yield group (HR = 0.72; 95% CI = 0.62–0.84; P < 0.01). Subset analysis of neoadjuvant-treated patients demonstrated a survival benefit of high lymph node yield on overall survival (HR = 0.82; 95% CI = 0.73–0.92; P < 0.01).

Conclusion:
This meta-analysis demonstrates the benefit of an increased lymph node yield from esophagectomy on overall and disease-free survival. In addition, a survival benefit of a high lymph node yield was demonstrated in patients receiving neoadjuvant therapy followed by esophagectomy.
Background selection and the statistics of population differentiation: consequences for detecting local adaptation
Authors: Matthey-Doret Remi , Whitlock Michael C. 
Published: May 2018

AbstractBackground selection is a process whereby recurrent deleterious mutations cause a decrease in the effective population size and genetic diversity at linked loci. Several authors have suggested that variation in the intensity of background selection could cause variation inFSTacross the genome, which could confound signals of local adaptation in genome scans. We performed realistic simulations of DNA sequences, using parameter estimates from humans and sticklebacks, to investigate how variation in the intensity of background selection affects different statistics of population differentiation. We show that, in populations connected by gene flow, Weir & Cockerham’s (1984) estimator ofFSTis largely insensitive to locus-to-locus variation in the intensity of background selection. UnlikeFST, however,dXYis negatively correlated with background selection. We also show that background selection does not greatly affect the false positive rate inFSToutlier studies. Overall, our study indicates that background selection will not greatly interfere with finding the variants responsible for local adaptation.
Mapping molecular HLA typing data to UNOS antigen equivalents for improved virtual crossmatch
Authors: Kaur Navchetan , Kransdorf Evan P. , Pando Marcelo J , Maiers Martin , Ray Bryan , Lee Jar-How , Lalli Peter , Murphey Cathi L , Bray Robert A , Gragert Loren 
Published: May 2018

AbstractBackgroundVirtual crossmatch utilizes HLA typing and antibody screen assay data as a part of organ offers in deceased donor allocation systems. Histocompatibility labs must convert molecular HLA typings to antigen equivalencies for entry into the United Network for Organ Sharing (UNOS) UNet system. While an Organ Procurement and Transplantation Network (OPTN) policy document provides general guidelines for conversion, the process is complex because no antigen mapping table is available. We present a UNOS antigen equivalency table for all IMGT/HLA alleles at the A, B, C, DRB1, DRB3/4/5, DQA1, and DQB1 loci.MethodsAn automated script was developed to generate a UNOS antigen equivalency table. Data sources used in the conversion algorithm included the World Marrow Donor Association(WMDA) antigen table, the HLA Dictionary, and UNOS-provided tables. To validate antigen mappings, we converted National Marrow Donor Program (NMDP) high resolution allele frequencies to antigen equivalents and compared with the UNOS Calculated Panel Reactive Antibodies (CPRA) reference panel.ResultsNormalized frequency similarity scores between independent NMDP and UNOS panels for 4 US population categories (Caucasian, Hispanic, African American and Asian/Pacific Islander) ranged from 0.85 to 0.97, indicating correct antigen mapping. An open source web application (ALLele to ANtigen (“ALLAN”)) and web services were also developed to map unambiguous and ambiguous HLA typing data to UNOS antigen equivalents based on NMDP population-specific allele frequencies (http://www.transplanttoolbox.org).ConclusionsThis tool sets a foundation for using molecular HLA typing to compute the virtual crossmatch and may aid in reducing typing discrepancies in UNet.
Photoacoustic imaging for the prediction and assessment of response to radiotherapyin vivo
Authors: Martinho Costa Márcia , Shah Anant , Rivens Ian , Box Carol , O’Shea Tuathan , Bamber Jeffrey , Haar Gail ter 
Published: May 2018

AbstractRadiotherapy is commonly used for cancer therapy, although its efficacy is reduced in hypoxic regions of tumours. Photoacoustic imaging (PAI) is an emergent, non-invasive imaging technique that allows the measurement of blood oxygen saturation (sO2) which inversely correlates with hypoxia in tissue. The potential use of PAI as a prognostic tool for radiotherapy outcome was investigated in a head and neck cancer modelin vivo. PAI was performed before delivering a single fraction (10, 20 or 30 Gy) treatment. The results show that tumours with pre-treatment higher blood sO2responded better than those with lower levels in the 10 and 20 Gy groups. For the 30 Gy group, treatment response was independent of blood sO2. The haemoglobin content of the tumours was not correlated with their response to any of the radiation doses studied. Changes in sO2, monitored at 24 h and 96 h following 10 and 20 Gy doses, showed that tumours that were subsequently unresponsive to treatment had an increase in blood sO2at both time points compared to those which subsequently regressed after radiotherapy. The results suggest that sO2values measured by photoacoustic imaging can be used before, and shortly after, irradiation to predict subsequent treatment response.
Physiological starvation increases EGF-Ras-MAPK pathway activity duringC. elegansvulval induction
Authors: Grimbert Stéphanie , Vargas Velazquez Amhed Missael , Braendle Christian 
Published: May 2018

AbstractStudying how molecular pathways respond to ecologically relevant environmental variation is fundamental to understand organismal development and its evolution. Here we characterize how starvation modulatesCaenorhabditis elegansvulval cell fate patterning – an environmentally sensitive process, with a nevertheless robust output. Past research has shown many vulval mutants affecting EGF-Ras-MAPK, Delta-Notch and Wnt pathways to be suppressed by environmental factors, such as starvation. Here we aimed to resolve previous, seemingly contradictory, observations on how starvation modulates levels of vulval induction. Using the strong starvation suppression of the Vulvaless phenotype oflin-3/egfreduction-of-function mutations as an experimental paradigm, we first tested for a possible involvement of the sensory system in relaying starvation signals to affect vulval induction: mutation of various sensory inputs, DAF-2/Insulin or DAF-7/TGF-βsignaling did not abolishlin-3(rf)starvation suppression. In contrast, nutrient deprivation induced by mutation of the intestinal peptide transporter genepept-1or the TOR pathway componentrsks-1(the orthologue of mammalian P70S6K) very strongly suppressedlin-3(rf)mutant phenotypes. Therefore, physiologically starved animals induced by these mutations tightly recapitulated the effects of external starvation on vulval induction. While both starvation andpept-1RNAi were sufficient to increase Ras and Notch pathway activities in vulval cells, the highly penetrant Vulvaless phenotype of a tissue-specific null allele oflin-3was not suppressed by either condition. This and additional results indicate that partiallin-3expression is required for starvation to affect vulval induction. These results suggest a cross-talk between nutrient deprivation, TOR-S6K and EGF-Ras-MAPK signaling duringC. elegansvulval induction.
Continuity and discontinuity in human cortical development and change from embryonic stages to old age
Authors: Fjell Anders M , Chen Chi-Hua , Sederevicius Donatas , Sneve Markus H , Gryde Håkon , Krogsrud Stine K , Amlien Inge , Ferschmann Lia , Ness Hedda , Folvik Line , Beck Dani , Mowinckel Athanasia M , Tamnes Christian K , Westerhausen René , Håberg Asta K. , Dale Anders M , Walhovd Kristine B 
Published: May 2018

AbstractThe human cerebral cortex is highly regionalized. We aimed to test whether principles of regionalization could be traced from embryonic development throughout the human lifespan. A data-driven fuzzy-clustering approach was used to identify regions of coordinated longitudinal development of cortical surface area (SA) and thickness (CT) over 1.5 years (n = 301, 4-12 years). First, the SA clusters were compared to patterns from embryonic cortical development. The earliest sign of cortical regionalization is the emergence of morphometric gradients in the cerebral vesicles, with a major gradient running along the anterior-posterior (AP) axis. We found that the principal divide for the developmental SA clusters extended from the inferior-posterior to the superior-anterior cortex, corresponding to the embryonic morphometric AP gradient. Second, embryonic factors showing a clear AP gradient were identified, and tests revealed significant differences in gene expression of these factors between the anterior and posterior clusters. Further, each identified developmental SA and CT cluster showed distinguishable lifespan trajectories in a larger longitudinal dataset (4-88 years, 1633 observations). This means that regions that developed together also changed together throughout life, demonstrating continuity in regionalization of cortical changes. The AP divide in SA development also characterized genetic patterning obtained in an adult twin sample, but otherwise regionalized CT development adhered more to the genetic boundaries. Finally, SA and CT clusters showed differential relationships to cognitive functions. In sum, the results suggest that development of cortical regionalization is a continuous process from the embryonic stage throughout human life.Significance statement (120 words)The protomap and the radial unit theories of brain development have shown that graded expression patterns of several factors are responsible for shaping the ultimately highly partitioned and specialized neocortical landscape. The present study shows that the major anterior-posterior gradient of embryonic development can be detected in the regional cortical expansion profiles of children. The study further demonstrates that brain regions that develop together during childhood also tend to change together throughout the lifespan. This suggests that regional cortical development is a continuous process through the entire life, and that early-life factors have life-long impacts on this process.
Temporal changes in gut microbiota and signaling molecules of the gut–brain axis in mice fed meat protein diets
Authors: Xie Yunting , Zhou Guanghong , Wang Chao , Xu Xinglian , Li Chunbao 
Published: May 2018

AbstractThe purpose of this study was to characterize the dynamical changes of gut microbiota and explore the influence on bidirectional communications between the gut and the brain during a relatively long-term intake of different protein diets. The C57BL/6J mice were fed casein, soy protein and four kinds of processed meat proteins at a normal dose of 20% for 8 months. Protein diets dramatically affected the microbial composition and function and also the signaling molecule levels of the gut–brain axis in a dynamic manner, which consequently affected growth performance. Alistipes, Clostridiales vadinBB60, Anaerotruncus, Blautia and Oscillibacter had a relatively fast response to the diet, while Bacteroidales S24-7, Ruminiclostridium, Ruminococcaceae UCG-014, Coriobacteriaceae UCG-002 and Bilophila responded slowly. Rikenellaceae RC9 gut, Faecalibaculum and Lachnospiraceae showed a continuous change with feeding time. Bacteroidales S24-7 abundance increased from 4 months to 8 months, whereas those of Rikenellaceae RC9 gut, Akkermansia, Alistipes and Anaerotruncus remarkably decreased. Five and fifteen biological functions of microbiota were affected at 4 months and 8 months, respectively, and sixteen functions were observed to change over feeding time. Moreover, 28 and 48 specific operational taxonomy units were associated with the regulation of serotonin, peptide YY, leptin and insulin levels at two time points. Ruminococcaceae was positively associated with Lachnospiraceae and negatively associated with Bacteroidales S24-7. These results give an important insight into the effect of gut microbiota on the bidirectional communications between the gut and the brain under a certain type of diet.ImportanceMany gastrointestinal and neuropsychiatric disorders may have a common pathophysiologic mechanism, involving bidirectional brain–gut axis signaling through humoral and neural pathways. The gut microbiota plays an important role in the communications between the gut and the brain. Recent evidence suggests that a growing number of subjects suffer from the above disorders. The significance of this study lies in the finding that long-term intake of different proteins at a normal dose induces dynamic alterations of specific microbiota in mice, which consequently affect bidirectional communications between the gut and the brain and results in different growth performance through dynamically regulating signaling molecule levels. Furthermore, this study indicates that intake of the same diet for a long time, irrespective of the diet source, may have an adverse effect on host health by altering gut microbiota.